A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.

In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.

“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.

The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.

“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.

“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.

Lessons from the past

During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.

There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak. 

An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.

In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.

These include:

• Clear care pathways for those who are suicidal.
• Remote or digital assessments for patients currently under the care of a mental health professional.
• Staff training to support new ways of working.
• Increased support for mental health helplines.
• Providing easily accessible grief counseling for those who have lost a loved one to the virus.
• Financial safety nets and labor market programs.
• Dissemination of evidence-based online interventions.

Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.

“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.

Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
 

Concerning spike in gun sales

Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.

“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.

Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.

In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported. 

In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.

“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.

Dr. Fleegler and colleagues said it’s also important to realize that firearm-related suicides were mounting well before COVID-19 hit. From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.

“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.

This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
 

A version of this article originally appeared on Medscape.com.

A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.

In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.

“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.

The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.

“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.

“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.

Lessons from the past

During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.

There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak. 

An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.

In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.

These include:

• Clear care pathways for those who are suicidal.
• Remote or digital assessments for patients currently under the care of a mental health professional.
• Staff training to support new ways of working.
• Increased support for mental health helplines.
• Providing easily accessible grief counseling for those who have lost a loved one to the virus.
• Financial safety nets and labor market programs.
• Dissemination of evidence-based online interventions.

Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.

“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.

Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
 

Concerning spike in gun sales

Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.

“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.

Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.

In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported. 

In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.

“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.

Dr. Fleegler and colleagues said it’s also important to realize that firearm-related suicides were mounting well before COVID-19 hit. From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.

“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.

This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
 

A version of this article originally appeared on Medscape.com.

A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.

In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.

“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.

The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.

“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.

“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.

Lessons from the past

During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.

There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak. 

An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.

In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.

These include:

• Clear care pathways for those who are suicidal.
• Remote or digital assessments for patients currently under the care of a mental health professional.
• Staff training to support new ways of working.
• Increased support for mental health helplines.
• Providing easily accessible grief counseling for those who have lost a loved one to the virus.
• Financial safety nets and labor market programs.
• Dissemination of evidence-based online interventions.

Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.

“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.

Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
 

Concerning spike in gun sales

Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.

“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.

Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.

In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported. 

In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.

“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.

Dr. Fleegler and colleagues said it’s also important to realize that firearm-related suicides were mounting well before COVID-19 hit. From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.

“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.

This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
 

A version of this article originally appeared on Medscape.com.

Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.¹ Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.

Presentation and cardiac risks from COVID-19

Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.² Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.³

The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).⁴ Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.⁵

Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.⁶

Acute cardiac injuries in COVID-19

Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.⁷ A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.³ More recent reports showed up to 28% of hospitalized patients had a myocardial injury.³

It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.³ The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.

In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.⁸

ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.³ ACI was higher in nonsurvivors (59%) than in survivors (1%).⁸ ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).⁹ Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).³

Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.^3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.³

The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.³

Management of acute cardiac issues in COVID-19

There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.¹⁰

There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.^3,11,12

Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.¹²

Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.¹³ Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.¹²

Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.¹¹ Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.

Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.^2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.^10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.

Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.^2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.

Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.¹⁴ Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.

Case examples

1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?

This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.

Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.

2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?

A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
 

Controversy on ACEI/ARB

The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.¹⁵

ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,¹⁶ though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.¹⁷

The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.¹⁸

Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.³

Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.¹⁹ However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.¹²

Cardiac concern about hydroxychloroquine and chloroquine

Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.²⁰ An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.²¹ HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.²²

Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.

HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.²³

Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.¹²
 

Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

Key points

• Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
• A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
• Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
• Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
• ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
• With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
• There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().

References

1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.

2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.

3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.

4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.

5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.

6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.

7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.

8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.

10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.

11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.

12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.

13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.

14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.

15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.

16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.

17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.

18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.

19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.

20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.

21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.

22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.

23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.¹ Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.

Presentation and cardiac risks from COVID-19

Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.² Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.³

The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).⁴ Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.⁵

Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.⁶

Acute cardiac injuries in COVID-19

Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.⁷ A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.³ More recent reports showed up to 28% of hospitalized patients had a myocardial injury.³

It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.³ The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.

In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.⁸

ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.³ ACI was higher in nonsurvivors (59%) than in survivors (1%).⁸ ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).⁹ Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).³

Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.^3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.³

The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.³

Management of acute cardiac issues in COVID-19

There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.¹⁰

There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.^3,11,12

Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.¹²

Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.¹³ Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.¹²

Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.¹¹ Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.

Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.^2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.^10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.

Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.^2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.

Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.¹⁴ Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.

Case examples

1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?

This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.

Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.

2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?

A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
 

Controversy on ACEI/ARB

The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.¹⁵

ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,¹⁶ though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.¹⁷

The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.¹⁸

Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.³

Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.¹⁹ However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.¹²

Cardiac concern about hydroxychloroquine and chloroquine

Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.²⁰ An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.²¹ HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.²²

Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.

HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.²³

Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.¹²
 

Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

Key points

• Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
• A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
• Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
• Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
• ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
• With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
• There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().

References

1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.

2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.

3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.

4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.

5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.

6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.

7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.

8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.

10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.

11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.

12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.

13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.

14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.

15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.

16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.

17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.

18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.

19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.

20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.

21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.

22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.

23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.¹ Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.

Presentation and cardiac risks from COVID-19

Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.² Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.³

The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).⁴ Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.⁵

Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.⁶

Acute cardiac injuries in COVID-19

Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.⁷ A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.³ More recent reports showed up to 28% of hospitalized patients had a myocardial injury.³

It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.³ The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.

In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.⁸

ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.³ ACI was higher in nonsurvivors (59%) than in survivors (1%).⁸ ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).⁹ Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).³

Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.^3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.³

The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.³

Management of acute cardiac issues in COVID-19

There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.¹⁰

There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.^3,11,12

Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.¹²

Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.¹³ Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.¹²

Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.¹¹ Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.

Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.^2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.^10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.

Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.^2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.

Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.¹⁴ Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.

Case examples

1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?

This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.

Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.

2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?

A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
 

Controversy on ACEI/ARB

The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.¹⁵

ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,¹⁶ though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.¹⁷

The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.¹⁸

Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.³

Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.¹⁹ However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.¹²

Cardiac concern about hydroxychloroquine and chloroquine

Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.²⁰ An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.²¹ HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.²²

Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.

HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.²³

Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.¹²
 

Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

Key points

• Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
• A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
• Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
• Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
• ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
• With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
• There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().

References

1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.

2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.

3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.

4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.

5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.

6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.

7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.

8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.

10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.

11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.

12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.

13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.

14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.

15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.

16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.

17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.

18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.

19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.

20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.

21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.

22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.

23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

The risk for suicide is higher at night than at any other time of day, new research shows.

In findings that may offer an opportunity for suicide prevention, investigators found that the risk of dying by suicide between midnight and 6:00 a.m. was roughly three times higher than at other times of day regardless of month, method of suicide, or a wide range of other factors.

“The take-home message is that helping at-risk patients sleep through the night may be an excellent way to reduce suicide risk,” lead author Andrew Tubbs, an MD/PhD candidate at the Sleep and Health Research Program, department of psychiatry, University of Arizona, Tucson, said in an interview.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.

Time, method of suicide

Previous research suggests that waking at night is linked to a heightened risk for suicidal thoughts and behaviors, the investigators note.

“The motivation for this study was to expand our understanding of factors that increase suicide risk at night. Since night length changes across seasons, we wondered if suicide risk at night would be lower during summer months and higher during winter months,” he said.

“Similarly, we thought the availability of some suicide methods may vary by time of day — for example, perhaps nighttime would involve more ‘silent’ methods, such as poisoning or asphyxiation, over ‘louder methods,’ such as firearms or vehicle suicides,” Mr. Tubbs added.

The investigators also examined whether the risk for nocturnal suicide was influenced by demographic or geographic factors.

They analyzed data on 35,338 suicides from the U.S. National Violent Death Reporting System for the years 2003-2010.

Time of suicide was divided into four categories: night (12:00 a.m.–5:59 a.m.), morning (6:00 a.m.–11:59 a.m.), afternoon (12:00 p.m.–5:59 p.m.), and evening (6:00 p.m.–11:59 p.m.).

Suicide methods included guns, asphyxiation, poisons, falls, vehicles, sharp weapons, drowning, and fire. Demographics included sex, age, race, and ethnicity. Geographic analyses were based on latitude (at or above 40° N or below 35° N) and region (West, Midwest, South, and Northeast).

Raw data revealed that more males than females died by suicide (n = 28,700 vs. 6636), that most suicides occurred in May (n = 3196), and that the most common method of suicide was by firearms (n = 21,937). Most suicides occurred in those aged 45-54 years (n = 7252) and in whites (n = 31,239) and non-Hispanics (33,384).

Interestingly, most suicides occurred during the afternoon (n = 11,381). Mr. Tubbs explained that suicides are more common during the day, typically around midday, when most people are awake, “so the ‘eligible’ population for suicide is highest at noon,” he said. However, this does not translate into level of risk, so the researchers accounted for nocturnal wakefulness in the analyses.

“When reason sleeps”

The incidence rate ratio at night was 3.18, significantly higher than at any other time of day across all months. The highest IRR was in May (3.90), and the lowest was in November (2.74).

An analysis of variance (ANOVA) for month and time of day indicated that the IRR varied significantly only by time of day (P < .001), not across months (P = .33) or by interaction (P = 1.00).

Initially, a two-way ANOVA showed that the risk for suicide varied both by time of day and by suicide method (both Ps < .001), but the interaction between them was not significant (P = .3026). The mean (SD) nocturnal IRR was 3.09 (.472) across all methods.

Although more than half of suicides involved firearms, “no method had a significantly higher risk at a specific time than any other method at that same time,” the authors note. In addition, an analysis of nocturnal risk by method showed no differences on the basis of sex, age, ethnicity, latitude, and region.

“There are probably many overlapping reasons why the risk of suicide is highest at night. Certainly, social and family supports are minimized if you are awake and everyone you know and love is asleep – you’re isolated, no one’s reaching out to you, and there’s no one there to stop you,” said Mr. Tubbs.

On the other hand, “recent evidence indicates nighttime changes in brain function can impair impulse control, decision making, and long-term planning, which can definitely increase suicidal behaviors.

“Whether these changes are due to sleep deprivation or circadian rhythms is unknown, but it is clearly dangerous to be awake when reason sleeps,” he said.

Clinicians who treat suicidal patients, said Mr. Tubbs, should ask about sleep. If a patient has a problem with sleep, cognitive-behavioral therapy for insomnia should be initiated. This first-line treatment, he said, is more effective and much safer than prescribing a hypnotic.
 

Difficult hours

Commenting on the study, Christopher W. Drapeau, PhD, of the department of education, Valparaiso University, Indiana, said that sleep disturbances “may be a modifiable risk factor for suicide, especially when sleep disturbances are cited by patients as a primary reason for wanting to attempt suicide.”

Dr. Drapeau, who was not involved in the study, said that this “presents an area for health professionals to focus on when developing treatment approaches based on patient information collected during suicide-risk screenings and comprehensive risk assessments.”

Also commenting on the study, Michael Nadorff, PhD, of the department of psychology, Mississippi State University, Starkville, who was not involved with the study, said the study findings are clinically relevant.

These data, he said, inform clinicians about when patients are most likely to be struggling with suicide intent and offer an opportunity to develop safety plans to mitigate suicide risk during these “difficult hours” when coping mechanisms are at a low ebb and sources of support are unavailable.

Support for the study was provided by grants from the National Institutes of Health and the Veterans Administration. Mr. Tubbs and Dr. Drapeau, and Dr. Nadorff report no relevant financial relationships.

This article first appeared on Medscape.com.

The risk for suicide is higher at night than at any other time of day, new research shows.

In findings that may offer an opportunity for suicide prevention, investigators found that the risk of dying by suicide between midnight and 6:00 a.m. was roughly three times higher than at other times of day regardless of month, method of suicide, or a wide range of other factors.

“The take-home message is that helping at-risk patients sleep through the night may be an excellent way to reduce suicide risk,” lead author Andrew Tubbs, an MD/PhD candidate at the Sleep and Health Research Program, department of psychiatry, University of Arizona, Tucson, said in an interview.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.

Time, method of suicide

Previous research suggests that waking at night is linked to a heightened risk for suicidal thoughts and behaviors, the investigators note.

“The motivation for this study was to expand our understanding of factors that increase suicide risk at night. Since night length changes across seasons, we wondered if suicide risk at night would be lower during summer months and higher during winter months,” he said.

“Similarly, we thought the availability of some suicide methods may vary by time of day — for example, perhaps nighttime would involve more ‘silent’ methods, such as poisoning or asphyxiation, over ‘louder methods,’ such as firearms or vehicle suicides,” Mr. Tubbs added.

The investigators also examined whether the risk for nocturnal suicide was influenced by demographic or geographic factors.

They analyzed data on 35,338 suicides from the U.S. National Violent Death Reporting System for the years 2003-2010.

Time of suicide was divided into four categories: night (12:00 a.m.–5:59 a.m.), morning (6:00 a.m.–11:59 a.m.), afternoon (12:00 p.m.–5:59 p.m.), and evening (6:00 p.m.–11:59 p.m.).

Suicide methods included guns, asphyxiation, poisons, falls, vehicles, sharp weapons, drowning, and fire. Demographics included sex, age, race, and ethnicity. Geographic analyses were based on latitude (at or above 40° N or below 35° N) and region (West, Midwest, South, and Northeast).

Raw data revealed that more males than females died by suicide (n = 28,700 vs. 6636), that most suicides occurred in May (n = 3196), and that the most common method of suicide was by firearms (n = 21,937). Most suicides occurred in those aged 45-54 years (n = 7252) and in whites (n = 31,239) and non-Hispanics (33,384).

Interestingly, most suicides occurred during the afternoon (n = 11,381). Mr. Tubbs explained that suicides are more common during the day, typically around midday, when most people are awake, “so the ‘eligible’ population for suicide is highest at noon,” he said. However, this does not translate into level of risk, so the researchers accounted for nocturnal wakefulness in the analyses.

“When reason sleeps”

The incidence rate ratio at night was 3.18, significantly higher than at any other time of day across all months. The highest IRR was in May (3.90), and the lowest was in November (2.74).

An analysis of variance (ANOVA) for month and time of day indicated that the IRR varied significantly only by time of day (P < .001), not across months (P = .33) or by interaction (P = 1.00).

Initially, a two-way ANOVA showed that the risk for suicide varied both by time of day and by suicide method (both Ps < .001), but the interaction between them was not significant (P = .3026). The mean (SD) nocturnal IRR was 3.09 (.472) across all methods.

Although more than half of suicides involved firearms, “no method had a significantly higher risk at a specific time than any other method at that same time,” the authors note. In addition, an analysis of nocturnal risk by method showed no differences on the basis of sex, age, ethnicity, latitude, and region.

“There are probably many overlapping reasons why the risk of suicide is highest at night. Certainly, social and family supports are minimized if you are awake and everyone you know and love is asleep – you’re isolated, no one’s reaching out to you, and there’s no one there to stop you,” said Mr. Tubbs.

On the other hand, “recent evidence indicates nighttime changes in brain function can impair impulse control, decision making, and long-term planning, which can definitely increase suicidal behaviors.

“Whether these changes are due to sleep deprivation or circadian rhythms is unknown, but it is clearly dangerous to be awake when reason sleeps,” he said.

Clinicians who treat suicidal patients, said Mr. Tubbs, should ask about sleep. If a patient has a problem with sleep, cognitive-behavioral therapy for insomnia should be initiated. This first-line treatment, he said, is more effective and much safer than prescribing a hypnotic.
 

Difficult hours

Commenting on the study, Christopher W. Drapeau, PhD, of the department of education, Valparaiso University, Indiana, said that sleep disturbances “may be a modifiable risk factor for suicide, especially when sleep disturbances are cited by patients as a primary reason for wanting to attempt suicide.”

Dr. Drapeau, who was not involved in the study, said that this “presents an area for health professionals to focus on when developing treatment approaches based on patient information collected during suicide-risk screenings and comprehensive risk assessments.”

Also commenting on the study, Michael Nadorff, PhD, of the department of psychology, Mississippi State University, Starkville, who was not involved with the study, said the study findings are clinically relevant.

These data, he said, inform clinicians about when patients are most likely to be struggling with suicide intent and offer an opportunity to develop safety plans to mitigate suicide risk during these “difficult hours” when coping mechanisms are at a low ebb and sources of support are unavailable.

Support for the study was provided by grants from the National Institutes of Health and the Veterans Administration. Mr. Tubbs and Dr. Drapeau, and Dr. Nadorff report no relevant financial relationships.

This article first appeared on Medscape.com.

The risk for suicide is higher at night than at any other time of day, new research shows.

In findings that may offer an opportunity for suicide prevention, investigators found that the risk of dying by suicide between midnight and 6:00 a.m. was roughly three times higher than at other times of day regardless of month, method of suicide, or a wide range of other factors.

“The take-home message is that helping at-risk patients sleep through the night may be an excellent way to reduce suicide risk,” lead author Andrew Tubbs, an MD/PhD candidate at the Sleep and Health Research Program, department of psychiatry, University of Arizona, Tucson, said in an interview.

The study was published in the March/April issue of the Journal of Clinical Psychiatry.

Time, method of suicide

Previous research suggests that waking at night is linked to a heightened risk for suicidal thoughts and behaviors, the investigators note.

“The motivation for this study was to expand our understanding of factors that increase suicide risk at night. Since night length changes across seasons, we wondered if suicide risk at night would be lower during summer months and higher during winter months,” he said.

“Similarly, we thought the availability of some suicide methods may vary by time of day — for example, perhaps nighttime would involve more ‘silent’ methods, such as poisoning or asphyxiation, over ‘louder methods,’ such as firearms or vehicle suicides,” Mr. Tubbs added.

The investigators also examined whether the risk for nocturnal suicide was influenced by demographic or geographic factors.

They analyzed data on 35,338 suicides from the U.S. National Violent Death Reporting System for the years 2003-2010.

Time of suicide was divided into four categories: night (12:00 a.m.–5:59 a.m.), morning (6:00 a.m.–11:59 a.m.), afternoon (12:00 p.m.–5:59 p.m.), and evening (6:00 p.m.–11:59 p.m.).

Suicide methods included guns, asphyxiation, poisons, falls, vehicles, sharp weapons, drowning, and fire. Demographics included sex, age, race, and ethnicity. Geographic analyses were based on latitude (at or above 40° N or below 35° N) and region (West, Midwest, South, and Northeast).

Raw data revealed that more males than females died by suicide (n = 28,700 vs. 6636), that most suicides occurred in May (n = 3196), and that the most common method of suicide was by firearms (n = 21,937). Most suicides occurred in those aged 45-54 years (n = 7252) and in whites (n = 31,239) and non-Hispanics (33,384).

Interestingly, most suicides occurred during the afternoon (n = 11,381). Mr. Tubbs explained that suicides are more common during the day, typically around midday, when most people are awake, “so the ‘eligible’ population for suicide is highest at noon,” he said. However, this does not translate into level of risk, so the researchers accounted for nocturnal wakefulness in the analyses.

“When reason sleeps”

The incidence rate ratio at night was 3.18, significantly higher than at any other time of day across all months. The highest IRR was in May (3.90), and the lowest was in November (2.74).

An analysis of variance (ANOVA) for month and time of day indicated that the IRR varied significantly only by time of day (P < .001), not across months (P = .33) or by interaction (P = 1.00).

Initially, a two-way ANOVA showed that the risk for suicide varied both by time of day and by suicide method (both Ps < .001), but the interaction between them was not significant (P = .3026). The mean (SD) nocturnal IRR was 3.09 (.472) across all methods.

Although more than half of suicides involved firearms, “no method had a significantly higher risk at a specific time than any other method at that same time,” the authors note. In addition, an analysis of nocturnal risk by method showed no differences on the basis of sex, age, ethnicity, latitude, and region.

“There are probably many overlapping reasons why the risk of suicide is highest at night. Certainly, social and family supports are minimized if you are awake and everyone you know and love is asleep – you’re isolated, no one’s reaching out to you, and there’s no one there to stop you,” said Mr. Tubbs.

On the other hand, “recent evidence indicates nighttime changes in brain function can impair impulse control, decision making, and long-term planning, which can definitely increase suicidal behaviors.

“Whether these changes are due to sleep deprivation or circadian rhythms is unknown, but it is clearly dangerous to be awake when reason sleeps,” he said.

Clinicians who treat suicidal patients, said Mr. Tubbs, should ask about sleep. If a patient has a problem with sleep, cognitive-behavioral therapy for insomnia should be initiated. This first-line treatment, he said, is more effective and much safer than prescribing a hypnotic.
 

Difficult hours

Commenting on the study, Christopher W. Drapeau, PhD, of the department of education, Valparaiso University, Indiana, said that sleep disturbances “may be a modifiable risk factor for suicide, especially when sleep disturbances are cited by patients as a primary reason for wanting to attempt suicide.”

Dr. Drapeau, who was not involved in the study, said that this “presents an area for health professionals to focus on when developing treatment approaches based on patient information collected during suicide-risk screenings and comprehensive risk assessments.”

Also commenting on the study, Michael Nadorff, PhD, of the department of psychology, Mississippi State University, Starkville, who was not involved with the study, said the study findings are clinically relevant.

These data, he said, inform clinicians about when patients are most likely to be struggling with suicide intent and offer an opportunity to develop safety plans to mitigate suicide risk during these “difficult hours” when coping mechanisms are at a low ebb and sources of support are unavailable.

Support for the study was provided by grants from the National Institutes of Health and the Veterans Administration. Mr. Tubbs and Dr. Drapeau, and Dr. Nadorff report no relevant financial relationships.

This article first appeared on Medscape.com.

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

In 1966 I was struggling with the decision of whether to become an art historian or go to medical school. I decided corporate ladder climbs and tenure chases were not for me. I wanted to be my own boss. I reckoned that medicine would offer me rock-solid job security and a comfortable income that I could adjust to my needs simply by working harder. In my Norman Rockwell–influenced view of the world, there would always be sick children. There would never be a quiet week or even a day when I would have to worry about not having an income.

Tomacco/iStock/Getty Images

So it was an idyllic existence for decades, tarnished only slightly when corporate entities began gobbling up owner-operator practices. But I never envisioned a pandemic that would turn the world – including its pediatricians – upside down. For the last several weeks as I pedal past my old office, I am dumbstruck by the empty parking lot. For the present I appear to be buffered by my retirement, but know that many of you are under serious financial pressure as a result of the pandemic.

We are all yearning to return to business as usual, but we know that it isn’t going to happen because everything has changed. The usual has yet to be defined. When you finally reopen your offices, you will be walking into a strange and eerie new normal. Initially you may struggle to make it feel like nothing has changed, but very quickly the full force of the postpandemic tsunami will hit us all broadside. In 2 years, the ship may still be rocking but what will clinical pediatrics look like in the late spring of 2022?

Will the patient mix have shifted even more toward behavioral and mental health complaints as a ripple effect of the pandemic’s emotional turmoil? Will more parents have begun to realize that they can manage minor complaints without an office visit? Will your waiting room have become a maze of plexiglass barriers to separate the sick from the well? Has the hospital invested hundreds of thousands of dollars in a ventilation system in hopes of minimizing contagion in your exam rooms? Maybe you will have instituted an appointment schedule with sick visits in the morning and well checks in the afternoon. Or you may no longer have a waiting room because patients are queuing in their cars in the parking lot. Your support staff may be rollerskating around like carhops at a drive-in recording histories and taking vital signs.

Telemedicine will hopefully have gone mainstream with more robust guidelines for billing and quality control. Medical schools may be devoting more attention to teaching student how to assess remotely. Parents may now be equipped with a tool kit of remote sensors so that you can assess their child’s tympanic membranes, pulse rate, oxygen saturation, and blood pressure on your office computer screen.

Will the EHR finally have begun to emerge from its awkward and at times painful adolescence into an easily accessible and transportable nationwide data bank that includes immunization records for all ages? Patients may have been asked or ordered to allow their cell phones to be used as tracking devices for serious communicable diseases. How many vaccine-resistant people will have responded to the pandemic by deciding that immunizations are worth the minimal risks? I fear not many.

How many of your colleagues will have left pediatrics and heeded the call for more epidemiologists? Will you be required to take a CME course in ventilation management? The good news may be that to keep the pediatric workforce robust the government has decided to forgive your student loans.

None of these changes may have come to pass because we have notoriously short memories. But I am sure that we will all still bear the deep scars of this world changing event.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

In 1966 I was struggling with the decision of whether to become an art historian or go to medical school. I decided corporate ladder climbs and tenure chases were not for me. I wanted to be my own boss. I reckoned that medicine would offer me rock-solid job security and a comfortable income that I could adjust to my needs simply by working harder. In my Norman Rockwell–influenced view of the world, there would always be sick children. There would never be a quiet week or even a day when I would have to worry about not having an income.

Tomacco/iStock/Getty Images

So it was an idyllic existence for decades, tarnished only slightly when corporate entities began gobbling up owner-operator practices. But I never envisioned a pandemic that would turn the world – including its pediatricians – upside down. For the last several weeks as I pedal past my old office, I am dumbstruck by the empty parking lot. For the present I appear to be buffered by my retirement, but know that many of you are under serious financial pressure as a result of the pandemic.

We are all yearning to return to business as usual, but we know that it isn’t going to happen because everything has changed. The usual has yet to be defined. When you finally reopen your offices, you will be walking into a strange and eerie new normal. Initially you may struggle to make it feel like nothing has changed, but very quickly the full force of the postpandemic tsunami will hit us all broadside. In 2 years, the ship may still be rocking but what will clinical pediatrics look like in the late spring of 2022?

Will the patient mix have shifted even more toward behavioral and mental health complaints as a ripple effect of the pandemic’s emotional turmoil? Will more parents have begun to realize that they can manage minor complaints without an office visit? Will your waiting room have become a maze of plexiglass barriers to separate the sick from the well? Has the hospital invested hundreds of thousands of dollars in a ventilation system in hopes of minimizing contagion in your exam rooms? Maybe you will have instituted an appointment schedule with sick visits in the morning and well checks in the afternoon. Or you may no longer have a waiting room because patients are queuing in their cars in the parking lot. Your support staff may be rollerskating around like carhops at a drive-in recording histories and taking vital signs.

Telemedicine will hopefully have gone mainstream with more robust guidelines for billing and quality control. Medical schools may be devoting more attention to teaching student how to assess remotely. Parents may now be equipped with a tool kit of remote sensors so that you can assess their child’s tympanic membranes, pulse rate, oxygen saturation, and blood pressure on your office computer screen.

Will the EHR finally have begun to emerge from its awkward and at times painful adolescence into an easily accessible and transportable nationwide data bank that includes immunization records for all ages? Patients may have been asked or ordered to allow their cell phones to be used as tracking devices for serious communicable diseases. How many vaccine-resistant people will have responded to the pandemic by deciding that immunizations are worth the minimal risks? I fear not many.

How many of your colleagues will have left pediatrics and heeded the call for more epidemiologists? Will you be required to take a CME course in ventilation management? The good news may be that to keep the pediatric workforce robust the government has decided to forgive your student loans.

None of these changes may have come to pass because we have notoriously short memories. But I am sure that we will all still bear the deep scars of this world changing event.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

In 1966 I was struggling with the decision of whether to become an art historian or go to medical school. I decided corporate ladder climbs and tenure chases were not for me. I wanted to be my own boss. I reckoned that medicine would offer me rock-solid job security and a comfortable income that I could adjust to my needs simply by working harder. In my Norman Rockwell–influenced view of the world, there would always be sick children. There would never be a quiet week or even a day when I would have to worry about not having an income.

Tomacco/iStock/Getty Images

So it was an idyllic existence for decades, tarnished only slightly when corporate entities began gobbling up owner-operator practices. But I never envisioned a pandemic that would turn the world – including its pediatricians – upside down. For the last several weeks as I pedal past my old office, I am dumbstruck by the empty parking lot. For the present I appear to be buffered by my retirement, but know that many of you are under serious financial pressure as a result of the pandemic.

We are all yearning to return to business as usual, but we know that it isn’t going to happen because everything has changed. The usual has yet to be defined. When you finally reopen your offices, you will be walking into a strange and eerie new normal. Initially you may struggle to make it feel like nothing has changed, but very quickly the full force of the postpandemic tsunami will hit us all broadside. In 2 years, the ship may still be rocking but what will clinical pediatrics look like in the late spring of 2022?

Will the patient mix have shifted even more toward behavioral and mental health complaints as a ripple effect of the pandemic’s emotional turmoil? Will more parents have begun to realize that they can manage minor complaints without an office visit? Will your waiting room have become a maze of plexiglass barriers to separate the sick from the well? Has the hospital invested hundreds of thousands of dollars in a ventilation system in hopes of minimizing contagion in your exam rooms? Maybe you will have instituted an appointment schedule with sick visits in the morning and well checks in the afternoon. Or you may no longer have a waiting room because patients are queuing in their cars in the parking lot. Your support staff may be rollerskating around like carhops at a drive-in recording histories and taking vital signs.

Telemedicine will hopefully have gone mainstream with more robust guidelines for billing and quality control. Medical schools may be devoting more attention to teaching student how to assess remotely. Parents may now be equipped with a tool kit of remote sensors so that you can assess their child’s tympanic membranes, pulse rate, oxygen saturation, and blood pressure on your office computer screen.

Will the EHR finally have begun to emerge from its awkward and at times painful adolescence into an easily accessible and transportable nationwide data bank that includes immunization records for all ages? Patients may have been asked or ordered to allow their cell phones to be used as tracking devices for serious communicable diseases. How many vaccine-resistant people will have responded to the pandemic by deciding that immunizations are worth the minimal risks? I fear not many.

How many of your colleagues will have left pediatrics and heeded the call for more epidemiologists? Will you be required to take a CME course in ventilation management? The good news may be that to keep the pediatric workforce robust the government has decided to forgive your student loans.

None of these changes may have come to pass because we have notoriously short memories. But I am sure that we will all still bear the deep scars of this world changing event.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It was unthinkable, but it has happened. A virulent and invisible virus, 10 microns in size, with no vaccine or cure yet, shut down our nation, the third largest country in the world with 330 million people. Overnight, our thriving cities became ghost towns. Schools were closed. Millions of businesses, restaurants, and stores were abruptly shuttered. Sporting events were instantly canceled. Air travel came to a halt.

The largest economy in the world started to tank. Millions of people lost their jobs and were forced to stay home. The vital structures of society were dismantled. Our vibrant culture came to a screeching halt. It’s a nightmare scenario that even the most imaginative science fiction writers could not have envisioned. By any measure, the coronavirus disease 2019 (COVID-19) pandemic unraveled everything, and became a human catastrophe and a social calamity reminiscent of the deadly 1918 influenza pandemic, or the devastating plagues that decimated Europe during the Middle Ages.

The human toll in death and suffering was the real disaster. Emergency departments and hospitals filled up with victims of the scourge, sickly and unable to breathe as the virus hijacked their red blood cells and lungs, and destroyed their alveoli. Compounding the disaster was a lack of medical supplies. The country was clearly caught off-guard, completely unprepared for the scale of the pandemic and the massive onslaught of desperately ill people requiring intensive care and special equipment. In addition, health care staff became stretched beyond the limit, and entire hospitals were transformed overnight into highly specialized ICUs. Medical care for millions with non-COVID-19 conditions was put on hold so that vital resources could be diverted to the desperately ill victims of these infections. Many physicians, nurses, and respiratory therapists—laudable heroes—succumbed to the perverse virus exhaled by their patients.

Insidious social effects

COVID-19 is not only a murderer, but also a thief. It stole our Spring; our religious holidays (Easter and Passover); classroom education in schools and colleges; the Prom; weddings; graduation ceremonies; proper funerals; concerts; football, basketball, hockey, and baseball games; Broadway shows; and even data from animal research. More important, it robbed us of our peace of mind, our liberty, and our pursuit of small pleasures such as family gatherings or schmoozing with friends at a nice restaurant. COVID-19 is a cruel, dastardly scoundrel.

I write this editorial as I sit at home, which I have not left for several weeks, like hundreds of millions in our country and around the world. We were all glued to TV news or the internet to learn about the latest updates, including the grim news of those who got infected, hospitalized, or passed away. Fear of dying permeated all age groups, especially those who were older and infirmed.

Making it worse was the relentless uncertainty. When will it end? Gradually or suddenly? When is it going to be safe to go to work again, or to visit our loved ones and our friends? When can we see our patients face-to-face instead of remotely by phone or video conferencing? When can we have live meetings instead of virtual video conferences? When will stores open so we can shop? When can we take our children or grandchildren to a baseball game or a show? Will the virus return next winter for another cycle of mayhem and social paralysis? When will the economy start to rebound, and how long will that take? Will our retirement accounts recoup their losses? So many questions with no clear answers. A malignant uncertainty, indeed.

And there are our patients who live with anxiety and depression, whose anguish is intensifying as they sit alone in their apartments or homes, struggling to cope with this sudden, overwhelming stress. How will they react to this pandemic? Obviously, a life-threatening event such as a deadly pandemic with no cure is likely to produce an acute stress reaction and, ultimately, posttraumatic stress disorder (PTSD). And if COVID-19 returns next year for another unwelcome visit, PTSD symptoms will get a booster shot and lead to severe anxiety, depression, or suicide. Psychiatrists and other mental health professionals, who were already stretched thin, must contend with another crisis that has destabilized millions of patients receiving psychiatric care, or new patients who seek help for themselves or their family members.

Continue to: One intervention that is emerging...

One intervention that is emerging on a large scale is online therapy. This includes reassurance and supportive therapy, cognitive-behavioral therapy, relaxation techniques, stress management, resilience training, mindfulness, and online group therapy. Those therapies can be effective for stress-induced anxiety and dysphoria when pharmacotherapy is not available, and can provide patients with tools and techniques that can be implemented by the patients themselves in the absence of a physician or nurse practitioner to prescribe a medication.

Lessons learned

This pandemic has taught us many lessons: that life as we know it should not be taken for granted, and can change drastically overnight; that human life is fragile and can be destroyed rapidly and ruthlessly on an unimaginable scale by an invisible enemy; that scientific drug development research by the often maligned pharmaceutical industry is indispensable to our well-being; that policymakers must always prepare for the worst and must have a well-designed disaster plan; that modifying human behavior and full compliance with public health measures are vital and can be the most effective way to prevent the spread of catastrophic pandemics, viral or otherwise; that we must all learn how to be resilient to cope with solitude and restricted mobility or socialization; that the human ingenuity and innovation that created technologies to enable virtual connectivity among us, even when we are isolated, has been a lifesaver during health crises such as the COVID-19 pandemic; that the clinicians and health care workers treating highly infectious and desperately ill patients are genuine heroes who deserve our respect and gratitude; and that magnificent altruism outstrips and outshines the selfish hoarding and profiteering that may emerge during life-threatening pandemics.

And that we shall overcome this horrid pandemic, a ghastly tribulation that changed everything.

It was unthinkable, but it has happened. A virulent and invisible virus, 10 microns in size, with no vaccine or cure yet, shut down our nation, the third largest country in the world with 330 million people. Overnight, our thriving cities became ghost towns. Schools were closed. Millions of businesses, restaurants, and stores were abruptly shuttered. Sporting events were instantly canceled. Air travel came to a halt.

The largest economy in the world started to tank. Millions of people lost their jobs and were forced to stay home. The vital structures of society were dismantled. Our vibrant culture came to a screeching halt. It’s a nightmare scenario that even the most imaginative science fiction writers could not have envisioned. By any measure, the coronavirus disease 2019 (COVID-19) pandemic unraveled everything, and became a human catastrophe and a social calamity reminiscent of the deadly 1918 influenza pandemic, or the devastating plagues that decimated Europe during the Middle Ages.

The human toll in death and suffering was the real disaster. Emergency departments and hospitals filled up with victims of the scourge, sickly and unable to breathe as the virus hijacked their red blood cells and lungs, and destroyed their alveoli. Compounding the disaster was a lack of medical supplies. The country was clearly caught off-guard, completely unprepared for the scale of the pandemic and the massive onslaught of desperately ill people requiring intensive care and special equipment. In addition, health care staff became stretched beyond the limit, and entire hospitals were transformed overnight into highly specialized ICUs. Medical care for millions with non-COVID-19 conditions was put on hold so that vital resources could be diverted to the desperately ill victims of these infections. Many physicians, nurses, and respiratory therapists—laudable heroes—succumbed to the perverse virus exhaled by their patients.

Insidious social effects

COVID-19 is not only a murderer, but also a thief. It stole our Spring; our religious holidays (Easter and Passover); classroom education in schools and colleges; the Prom; weddings; graduation ceremonies; proper funerals; concerts; football, basketball, hockey, and baseball games; Broadway shows; and even data from animal research. More important, it robbed us of our peace of mind, our liberty, and our pursuit of small pleasures such as family gatherings or schmoozing with friends at a nice restaurant. COVID-19 is a cruel, dastardly scoundrel.

I write this editorial as I sit at home, which I have not left for several weeks, like hundreds of millions in our country and around the world. We were all glued to TV news or the internet to learn about the latest updates, including the grim news of those who got infected, hospitalized, or passed away. Fear of dying permeated all age groups, especially those who were older and infirmed.

Making it worse was the relentless uncertainty. When will it end? Gradually or suddenly? When is it going to be safe to go to work again, or to visit our loved ones and our friends? When can we see our patients face-to-face instead of remotely by phone or video conferencing? When can we have live meetings instead of virtual video conferences? When will stores open so we can shop? When can we take our children or grandchildren to a baseball game or a show? Will the virus return next winter for another cycle of mayhem and social paralysis? When will the economy start to rebound, and how long will that take? Will our retirement accounts recoup their losses? So many questions with no clear answers. A malignant uncertainty, indeed.

And there are our patients who live with anxiety and depression, whose anguish is intensifying as they sit alone in their apartments or homes, struggling to cope with this sudden, overwhelming stress. How will they react to this pandemic? Obviously, a life-threatening event such as a deadly pandemic with no cure is likely to produce an acute stress reaction and, ultimately, posttraumatic stress disorder (PTSD). And if COVID-19 returns next year for another unwelcome visit, PTSD symptoms will get a booster shot and lead to severe anxiety, depression, or suicide. Psychiatrists and other mental health professionals, who were already stretched thin, must contend with another crisis that has destabilized millions of patients receiving psychiatric care, or new patients who seek help for themselves or their family members.

Continue to: One intervention that is emerging...

One intervention that is emerging on a large scale is online therapy. This includes reassurance and supportive therapy, cognitive-behavioral therapy, relaxation techniques, stress management, resilience training, mindfulness, and online group therapy. Those therapies can be effective for stress-induced anxiety and dysphoria when pharmacotherapy is not available, and can provide patients with tools and techniques that can be implemented by the patients themselves in the absence of a physician or nurse practitioner to prescribe a medication.

Lessons learned

This pandemic has taught us many lessons: that life as we know it should not be taken for granted, and can change drastically overnight; that human life is fragile and can be destroyed rapidly and ruthlessly on an unimaginable scale by an invisible enemy; that scientific drug development research by the often maligned pharmaceutical industry is indispensable to our well-being; that policymakers must always prepare for the worst and must have a well-designed disaster plan; that modifying human behavior and full compliance with public health measures are vital and can be the most effective way to prevent the spread of catastrophic pandemics, viral or otherwise; that we must all learn how to be resilient to cope with solitude and restricted mobility or socialization; that the human ingenuity and innovation that created technologies to enable virtual connectivity among us, even when we are isolated, has been a lifesaver during health crises such as the COVID-19 pandemic; that the clinicians and health care workers treating highly infectious and desperately ill patients are genuine heroes who deserve our respect and gratitude; and that magnificent altruism outstrips and outshines the selfish hoarding and profiteering that may emerge during life-threatening pandemics.

And that we shall overcome this horrid pandemic, a ghastly tribulation that changed everything.

It was unthinkable, but it has happened. A virulent and invisible virus, 10 microns in size, with no vaccine or cure yet, shut down our nation, the third largest country in the world with 330 million people. Overnight, our thriving cities became ghost towns. Schools were closed. Millions of businesses, restaurants, and stores were abruptly shuttered. Sporting events were instantly canceled. Air travel came to a halt.

The largest economy in the world started to tank. Millions of people lost their jobs and were forced to stay home. The vital structures of society were dismantled. Our vibrant culture came to a screeching halt. It’s a nightmare scenario that even the most imaginative science fiction writers could not have envisioned. By any measure, the coronavirus disease 2019 (COVID-19) pandemic unraveled everything, and became a human catastrophe and a social calamity reminiscent of the deadly 1918 influenza pandemic, or the devastating plagues that decimated Europe during the Middle Ages.

The human toll in death and suffering was the real disaster. Emergency departments and hospitals filled up with victims of the scourge, sickly and unable to breathe as the virus hijacked their red blood cells and lungs, and destroyed their alveoli. Compounding the disaster was a lack of medical supplies. The country was clearly caught off-guard, completely unprepared for the scale of the pandemic and the massive onslaught of desperately ill people requiring intensive care and special equipment. In addition, health care staff became stretched beyond the limit, and entire hospitals were transformed overnight into highly specialized ICUs. Medical care for millions with non-COVID-19 conditions was put on hold so that vital resources could be diverted to the desperately ill victims of these infections. Many physicians, nurses, and respiratory therapists—laudable heroes—succumbed to the perverse virus exhaled by their patients.

Insidious social effects

COVID-19 is not only a murderer, but also a thief. It stole our Spring; our religious holidays (Easter and Passover); classroom education in schools and colleges; the Prom; weddings; graduation ceremonies; proper funerals; concerts; football, basketball, hockey, and baseball games; Broadway shows; and even data from animal research. More important, it robbed us of our peace of mind, our liberty, and our pursuit of small pleasures such as family gatherings or schmoozing with friends at a nice restaurant. COVID-19 is a cruel, dastardly scoundrel.

I write this editorial as I sit at home, which I have not left for several weeks, like hundreds of millions in our country and around the world. We were all glued to TV news or the internet to learn about the latest updates, including the grim news of those who got infected, hospitalized, or passed away. Fear of dying permeated all age groups, especially those who were older and infirmed.

Making it worse was the relentless uncertainty. When will it end? Gradually or suddenly? When is it going to be safe to go to work again, or to visit our loved ones and our friends? When can we see our patients face-to-face instead of remotely by phone or video conferencing? When can we have live meetings instead of virtual video conferences? When will stores open so we can shop? When can we take our children or grandchildren to a baseball game or a show? Will the virus return next winter for another cycle of mayhem and social paralysis? When will the economy start to rebound, and how long will that take? Will our retirement accounts recoup their losses? So many questions with no clear answers. A malignant uncertainty, indeed.

And there are our patients who live with anxiety and depression, whose anguish is intensifying as they sit alone in their apartments or homes, struggling to cope with this sudden, overwhelming stress. How will they react to this pandemic? Obviously, a life-threatening event such as a deadly pandemic with no cure is likely to produce an acute stress reaction and, ultimately, posttraumatic stress disorder (PTSD). And if COVID-19 returns next year for another unwelcome visit, PTSD symptoms will get a booster shot and lead to severe anxiety, depression, or suicide. Psychiatrists and other mental health professionals, who were already stretched thin, must contend with another crisis that has destabilized millions of patients receiving psychiatric care, or new patients who seek help for themselves or their family members.

Continue to: One intervention that is emerging...

One intervention that is emerging on a large scale is online therapy. This includes reassurance and supportive therapy, cognitive-behavioral therapy, relaxation techniques, stress management, resilience training, mindfulness, and online group therapy. Those therapies can be effective for stress-induced anxiety and dysphoria when pharmacotherapy is not available, and can provide patients with tools and techniques that can be implemented by the patients themselves in the absence of a physician or nurse practitioner to prescribe a medication.

Lessons learned

This pandemic has taught us many lessons: that life as we know it should not be taken for granted, and can change drastically overnight; that human life is fragile and can be destroyed rapidly and ruthlessly on an unimaginable scale by an invisible enemy; that scientific drug development research by the often maligned pharmaceutical industry is indispensable to our well-being; that policymakers must always prepare for the worst and must have a well-designed disaster plan; that modifying human behavior and full compliance with public health measures are vital and can be the most effective way to prevent the spread of catastrophic pandemics, viral or otherwise; that we must all learn how to be resilient to cope with solitude and restricted mobility or socialization; that the human ingenuity and innovation that created technologies to enable virtual connectivity among us, even when we are isolated, has been a lifesaver during health crises such as the COVID-19 pandemic; that the clinicians and health care workers treating highly infectious and desperately ill patients are genuine heroes who deserve our respect and gratitude; and that magnificent altruism outstrips and outshines the selfish hoarding and profiteering that may emerge during life-threatening pandemics.

And that we shall overcome this horrid pandemic, a ghastly tribulation that changed everything.

A week after its launch, a new online registry has information on more than 2 dozen cases of pediatric cancer patients with COVID-19.

The registry, created by St. Jude Children’s Research Hospital in Memphis, Tenn., and the International Society of Paediatric Oncology, is the first global COVID-19 registry for children with cancer.

Clinicians enter cases through an online form, then complete 30- and 60-day follow-up reports via email. St. Jude compiles the data and releases regularly updated summaries, including the number of cases by country and by treatment. Eventually, researchers might be able to apply for access to the raw data for their own projects.

It’s all free of charge, said Carlos Rodriguez-Galindo, MD, chair of the department of global pediatric medicine at St. Jude.

The registry is hosted on a website called “The Global COVID-19 Observatory and Resource Center for Childhood Cancer.” In addition to the registry, the website has a resource library and a discussion forum where clinicians can exchange information.

Other COVID-19 cancer registries have launched recently as well, including registries created by the COVID-19 and Cancer Consortium and the American Society of Clinical Oncology. The idea is to compile and disseminate best practices and other information quickly amid concerns that immunosuppressed cancer patients might be especially vulnerable.

So far, that doesn’t seem to be the case for children. Their relative protection from the disease and serious complications seems to hold even when they have cancer, Dr. Rodriguez-Galindo said.

“When we talk with the people in China” the number of COVID-19 cases in children with cancer is “very small,” he said. There are a couple of reports from Europe finding the same thing, and the severity of COVID-19 also “seems to be lower than you would expect,” he added.

The new registry will help better define the situation, according to Dr. Rodriguez-Galindo.

St. Jude is working with European countries that have their own national pediatric cancer COVID-19 registries to share information. St. Jude’s ties with lower- and middle-income countries, established via the department of global pediatric medicine, should help populate the global registry as well.

Furthermore, international surveys are being planned to gauge the impact of COVID-19 on children with cancer and their access to care.

aotto@mdedge.com

A week after its launch, a new online registry has information on more than 2 dozen cases of pediatric cancer patients with COVID-19.

The registry, created by St. Jude Children’s Research Hospital in Memphis, Tenn., and the International Society of Paediatric Oncology, is the first global COVID-19 registry for children with cancer.

Clinicians enter cases through an online form, then complete 30- and 60-day follow-up reports via email. St. Jude compiles the data and releases regularly updated summaries, including the number of cases by country and by treatment. Eventually, researchers might be able to apply for access to the raw data for their own projects.

It’s all free of charge, said Carlos Rodriguez-Galindo, MD, chair of the department of global pediatric medicine at St. Jude.

The registry is hosted on a website called “The Global COVID-19 Observatory and Resource Center for Childhood Cancer.” In addition to the registry, the website has a resource library and a discussion forum where clinicians can exchange information.

Other COVID-19 cancer registries have launched recently as well, including registries created by the COVID-19 and Cancer Consortium and the American Society of Clinical Oncology. The idea is to compile and disseminate best practices and other information quickly amid concerns that immunosuppressed cancer patients might be especially vulnerable.

So far, that doesn’t seem to be the case for children. Their relative protection from the disease and serious complications seems to hold even when they have cancer, Dr. Rodriguez-Galindo said.

“When we talk with the people in China” the number of COVID-19 cases in children with cancer is “very small,” he said. There are a couple of reports from Europe finding the same thing, and the severity of COVID-19 also “seems to be lower than you would expect,” he added.

The new registry will help better define the situation, according to Dr. Rodriguez-Galindo.

St. Jude is working with European countries that have their own national pediatric cancer COVID-19 registries to share information. St. Jude’s ties with lower- and middle-income countries, established via the department of global pediatric medicine, should help populate the global registry as well.

Furthermore, international surveys are being planned to gauge the impact of COVID-19 on children with cancer and their access to care.

aotto@mdedge.com

A week after its launch, a new online registry has information on more than 2 dozen cases of pediatric cancer patients with COVID-19.

The registry, created by St. Jude Children’s Research Hospital in Memphis, Tenn., and the International Society of Paediatric Oncology, is the first global COVID-19 registry for children with cancer.

Clinicians enter cases through an online form, then complete 30- and 60-day follow-up reports via email. St. Jude compiles the data and releases regularly updated summaries, including the number of cases by country and by treatment. Eventually, researchers might be able to apply for access to the raw data for their own projects.

It’s all free of charge, said Carlos Rodriguez-Galindo, MD, chair of the department of global pediatric medicine at St. Jude.

The registry is hosted on a website called “The Global COVID-19 Observatory and Resource Center for Childhood Cancer.” In addition to the registry, the website has a resource library and a discussion forum where clinicians can exchange information.

Other COVID-19 cancer registries have launched recently as well, including registries created by the COVID-19 and Cancer Consortium and the American Society of Clinical Oncology. The idea is to compile and disseminate best practices and other information quickly amid concerns that immunosuppressed cancer patients might be especially vulnerable.

So far, that doesn’t seem to be the case for children. Their relative protection from the disease and serious complications seems to hold even when they have cancer, Dr. Rodriguez-Galindo said.

“When we talk with the people in China” the number of COVID-19 cases in children with cancer is “very small,” he said. There are a couple of reports from Europe finding the same thing, and the severity of COVID-19 also “seems to be lower than you would expect,” he added.

The new registry will help better define the situation, according to Dr. Rodriguez-Galindo.

St. Jude is working with European countries that have their own national pediatric cancer COVID-19 registries to share information. St. Jude’s ties with lower- and middle-income countries, established via the department of global pediatric medicine, should help populate the global registry as well.

Furthermore, international surveys are being planned to gauge the impact of COVID-19 on children with cancer and their access to care.

aotto@mdedge.com

One contentious issue during the COVID-19 crisis has been the appropriate selection and use of respiratory protective equipment (RPE) for healthcare workers (HCWs) in hospitals and long-term care settings. As of April 2020, discrepancies exist in the recommendations from health authorities such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Canadian Standards Association (CSA). The first of these recommends a surgical mask for routine care and a respirator for high-risk care such as aerosol-generating procedures, while the CDC recommends respirators for all aspects of patient care for these SARS-CoV-2–infected patients, and the CSA risk assessment tool would also result in selection of a respirator.^1-3

Given the contradictory guidance, we will discuss several important considerations for hospital leaders in the implementation of a healthcare respiratory protection program during the current pandemic, including a focused review of the empirical data on surgical mask vs face-fitted respirator (most commonly available in healthcare as N95 in North America), continuous use of the RPE throughout an entire shift vs targeted use when caring for patients, and key areas of uncertainty.

Surgical masks are traditionally used for protection against droplet transmission of respiratory infections, in which large droplets often fall to the ground within short distances; on the other hand, N95 respirators are used for much smaller airborne pathogens, which can remain suspended in the air for long periods of time. Although empiric studies have supported the superiority of respirators over surgical masks in simulated settings (frequently defined as a calculated concentration ratio outside vs inside the RPE), most clinical studies fail to demonstrate a difference in clinical outcomes such as the prevention of respiratory infection. For instance, an exposure study using saline aerosol to simulate viral particles showed that N95 respirators conferred up to 8 to 12 times greater protection against particulate penetration, compared with surgical masks.⁴ However, these advantages of respirators over surgical masks in carefully controlled laboratory studies do not seem to translate to decreased infection risk in real-world settings.

The effectiveness of N95 respirators vs surgical masks in preventing respiratory infections has been evaluated in a small number of clinical randomized, controlled trials (RCTs). We identified five systematic reviews and/or metanalyses published after 2010 and three RCTs published after 1990.^5-12 The RCTs used laboratory-confirmed respiratory virus or clinical infection in HCWs as a clinical outcome, but studies differed in the implementation of RPE use (ie, continuous or targeted use). In a systematic review and metanalysis, Long et al identified six RCTs (9,171 participants) and concluded that, with the exception of laboratory-confirmed bacterial colonization, N95 respirators did not reduce the rate of laboratory-­confirmed influenza, viral respiratory infections, or influenza-like illness among HCWs, compared with surgical masks.⁵ The authors noted risks of bias in these studies owing to the inability to blind and conceal allocation. In addition, the studies focused on infections that are known to transmit via droplet, such as influenza, so the results might not be applicable in the face of a new pandemic in which the important modes of transmission are not yet clear.

The evidence base evaluating continuous vs targeted use of RPE in healthcare settings is quite small. Continuous use refers to using the RPE during an entire shift, whereas targeted use involves using RPE only when caring for confirmed or suspected respiratory patients. In our literature review we identified only one RCT that included separate study arms for continuous and targeted N95 respirator use.¹³ The authors found a significantly lower rate of clinical respiratory illness among HCWs in the continuous-use group, compared with that in the targeted-use group. Limitations of the study included a relatively short follow-up of 4 weeks and uneven distribution of baseline characteristics, although the authors adjusted for these differences in their analysis. The study, however, did not compare continuous vs targeted use of surgical masks with regard to clinical outcomes. Based on the study results, we can only infer that continuous use of RPE, either surgical mask or N95 respirator, may provide additional benefit to HCWs vs targeted use only.

Given the lack of robust evidence informing continuous or targeted RPE use, we suggest some additional factors to guide decision making. In settings with high HCW compliance with universal RPE (above 50%), even noncompliant HCW are protected against clinical respiratory illness, which suggests a herd protective effect when universal RPE use is implemented, likely owing to the prevention of symptomatic or asymptomatic infectious spread among HCWs.¹⁴ It is important to note that the compliance rate may be limited by discomfort of prolonged wear of certain RPEs. One study reported that compliance rate is lower for continuous use (66%) than it is for targeted use (82%).¹³ Accumulated respiratory pathogen deposition on RPEs from an extended period of use that could result in self-­contamination to the wearer is a potential concern, although these risks must be balanced against the repeated donning and doffing required by targeted use. Pilot studies examining viral particles left on surgical masks after being worn for entire shifts (or as long as tolerated) found that there were significantly more viral particles detected after 6 hours of continuous wear, which may increase the risk of self-contamination.¹⁵

The current literature is applicable to infections that are known to spread via droplet contact, and this is a major limitation in generalizing the available evidence to the SARS-CoV-2 pandemic, in which debate persists regarding the exact mode of transmission. It is postulated that, even in infections traditionally considered to be spread by droplets, such as influenza, aerosol transmission may occur when HCWs are working in close proximity to the exposure source or when the droplet evaporates and becomes droplet nuclei. The United States National Academies of Science, Engineering, and Medicine expert consultation report, published in April 2020, concluded that current studies support the possibility of aerosolization of SARS-CoV-2 virus from normal breathing.¹⁶ As of April 2020, the WHO recommendation for SARS-CoV-2 is to use droplet contact precautions with a surgical mask for regular patient care and N95 respirator for aerosol-generating procedures.¹ Although we have not come across any studies specifically comparing the efficacy between surgical mask to N95 respirator protection while performing aerosol-generating procedures, a systematic review found that certain aerosol-generating procedures, such as endotracheal intubation and noninvasive ventilation, conferred a significantly higher risk of transmission of SARS-CoV-1 to HCWs in 2003.¹⁷ For the current crisis, the CDC is taking a cautious approach in which N95 respirators are recommended for HCWs caring for patients with confirmed or suspected SARS-CoV-2 infection if the supply chain is secure, with advice in place in times of RPE shortage, such as use of expired respirators, other types of equivalent respirators, or respirators not approved by the National Institute for Occupational Safety and Health, as well as optimization of administrative and engineering controls (eg, telemedicine, limiting patient and visitor numbers, physical barriers, optimizing ventilation systems).^2,18 This advice is unusual in terms of deviating from advising the most appropriate RPE, and we presume it reflects the present global supply problems.

RPEs are only one component of a necessary personal protective equipment ensemble. Although eye protection (goggles or face shields) is recommended by the WHO and CDC when caring for patients with SARS-CoV-2, there is considerable uncertainty regarding the incremental effectiveness of eye protection because such protection is usually worn in conjunction with RPE. A 2019 Cochrane review did not identify any good-quality studies that could inform judgments regarding the effectiveness of eye protective equipment,¹⁹ and a recent rapid review reporting on the efficacy of eye protection in primary care settings reached a similar conclusion.²⁰ A risk-based approach would be to include eye protection in a well-­designed personal protective equipment program.

In the absence of aerosol-generating procedures, N95 respirators confer no additional benefit in preventing HCW respiratory infections when droplet transmission is suspected. However, the applicability of the available evidence is limited given the uncertainties surrounding SARS-CoV-2 transmission. When RPE may become scarce during a pandemic, the risk of potential self-contamination must be weighed against RPE conservation strategies. RPE compliance, herd-protection effects of routine RPE use, and RPE contamination from prolonged use are therefore important elements to consider when implementing hospital policies regarding universal masking because they all impact the potential effectiveness of RPE.

At the present time we lack definitive evidence on the effectiveness of surgical masks vs respirators and continuous vs targeted RPE use in the hospital setting for SARS-CoV-2. If our goal is to minimize risk of HCW infection, continuous use of N95 respirator could be considered. However, a more pragmatic solution in the setting of a limited supply of N95 respirators would be continuous use of surgical masks while engaged in clinical care of patients under investigation or with confirmed COVID-19.

One contentious issue during the COVID-19 crisis has been the appropriate selection and use of respiratory protective equipment (RPE) for healthcare workers (HCWs) in hospitals and long-term care settings. As of April 2020, discrepancies exist in the recommendations from health authorities such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Canadian Standards Association (CSA). The first of these recommends a surgical mask for routine care and a respirator for high-risk care such as aerosol-generating procedures, while the CDC recommends respirators for all aspects of patient care for these SARS-CoV-2–infected patients, and the CSA risk assessment tool would also result in selection of a respirator.^1-3

Given the contradictory guidance, we will discuss several important considerations for hospital leaders in the implementation of a healthcare respiratory protection program during the current pandemic, including a focused review of the empirical data on surgical mask vs face-fitted respirator (most commonly available in healthcare as N95 in North America), continuous use of the RPE throughout an entire shift vs targeted use when caring for patients, and key areas of uncertainty.

Surgical masks are traditionally used for protection against droplet transmission of respiratory infections, in which large droplets often fall to the ground within short distances; on the other hand, N95 respirators are used for much smaller airborne pathogens, which can remain suspended in the air for long periods of time. Although empiric studies have supported the superiority of respirators over surgical masks in simulated settings (frequently defined as a calculated concentration ratio outside vs inside the RPE), most clinical studies fail to demonstrate a difference in clinical outcomes such as the prevention of respiratory infection. For instance, an exposure study using saline aerosol to simulate viral particles showed that N95 respirators conferred up to 8 to 12 times greater protection against particulate penetration, compared with surgical masks.⁴ However, these advantages of respirators over surgical masks in carefully controlled laboratory studies do not seem to translate to decreased infection risk in real-world settings.

The effectiveness of N95 respirators vs surgical masks in preventing respiratory infections has been evaluated in a small number of clinical randomized, controlled trials (RCTs). We identified five systematic reviews and/or metanalyses published after 2010 and three RCTs published after 1990.^5-12 The RCTs used laboratory-confirmed respiratory virus or clinical infection in HCWs as a clinical outcome, but studies differed in the implementation of RPE use (ie, continuous or targeted use). In a systematic review and metanalysis, Long et al identified six RCTs (9,171 participants) and concluded that, with the exception of laboratory-confirmed bacterial colonization, N95 respirators did not reduce the rate of laboratory-­confirmed influenza, viral respiratory infections, or influenza-like illness among HCWs, compared with surgical masks.⁵ The authors noted risks of bias in these studies owing to the inability to blind and conceal allocation. In addition, the studies focused on infections that are known to transmit via droplet, such as influenza, so the results might not be applicable in the face of a new pandemic in which the important modes of transmission are not yet clear.

The evidence base evaluating continuous vs targeted use of RPE in healthcare settings is quite small. Continuous use refers to using the RPE during an entire shift, whereas targeted use involves using RPE only when caring for confirmed or suspected respiratory patients. In our literature review we identified only one RCT that included separate study arms for continuous and targeted N95 respirator use.¹³ The authors found a significantly lower rate of clinical respiratory illness among HCWs in the continuous-use group, compared with that in the targeted-use group. Limitations of the study included a relatively short follow-up of 4 weeks and uneven distribution of baseline characteristics, although the authors adjusted for these differences in their analysis. The study, however, did not compare continuous vs targeted use of surgical masks with regard to clinical outcomes. Based on the study results, we can only infer that continuous use of RPE, either surgical mask or N95 respirator, may provide additional benefit to HCWs vs targeted use only.

Given the lack of robust evidence informing continuous or targeted RPE use, we suggest some additional factors to guide decision making. In settings with high HCW compliance with universal RPE (above 50%), even noncompliant HCW are protected against clinical respiratory illness, which suggests a herd protective effect when universal RPE use is implemented, likely owing to the prevention of symptomatic or asymptomatic infectious spread among HCWs.¹⁴ It is important to note that the compliance rate may be limited by discomfort of prolonged wear of certain RPEs. One study reported that compliance rate is lower for continuous use (66%) than it is for targeted use (82%).¹³ Accumulated respiratory pathogen deposition on RPEs from an extended period of use that could result in self-­contamination to the wearer is a potential concern, although these risks must be balanced against the repeated donning and doffing required by targeted use. Pilot studies examining viral particles left on surgical masks after being worn for entire shifts (or as long as tolerated) found that there were significantly more viral particles detected after 6 hours of continuous wear, which may increase the risk of self-contamination.¹⁵

The current literature is applicable to infections that are known to spread via droplet contact, and this is a major limitation in generalizing the available evidence to the SARS-CoV-2 pandemic, in which debate persists regarding the exact mode of transmission. It is postulated that, even in infections traditionally considered to be spread by droplets, such as influenza, aerosol transmission may occur when HCWs are working in close proximity to the exposure source or when the droplet evaporates and becomes droplet nuclei. The United States National Academies of Science, Engineering, and Medicine expert consultation report, published in April 2020, concluded that current studies support the possibility of aerosolization of SARS-CoV-2 virus from normal breathing.¹⁶ As of April 2020, the WHO recommendation for SARS-CoV-2 is to use droplet contact precautions with a surgical mask for regular patient care and N95 respirator for aerosol-generating procedures.¹ Although we have not come across any studies specifically comparing the efficacy between surgical mask to N95 respirator protection while performing aerosol-generating procedures, a systematic review found that certain aerosol-generating procedures, such as endotracheal intubation and noninvasive ventilation, conferred a significantly higher risk of transmission of SARS-CoV-1 to HCWs in 2003.¹⁷ For the current crisis, the CDC is taking a cautious approach in which N95 respirators are recommended for HCWs caring for patients with confirmed or suspected SARS-CoV-2 infection if the supply chain is secure, with advice in place in times of RPE shortage, such as use of expired respirators, other types of equivalent respirators, or respirators not approved by the National Institute for Occupational Safety and Health, as well as optimization of administrative and engineering controls (eg, telemedicine, limiting patient and visitor numbers, physical barriers, optimizing ventilation systems).^2,18 This advice is unusual in terms of deviating from advising the most appropriate RPE, and we presume it reflects the present global supply problems.

RPEs are only one component of a necessary personal protective equipment ensemble. Although eye protection (goggles or face shields) is recommended by the WHO and CDC when caring for patients with SARS-CoV-2, there is considerable uncertainty regarding the incremental effectiveness of eye protection because such protection is usually worn in conjunction with RPE. A 2019 Cochrane review did not identify any good-quality studies that could inform judgments regarding the effectiveness of eye protective equipment,¹⁹ and a recent rapid review reporting on the efficacy of eye protection in primary care settings reached a similar conclusion.²⁰ A risk-based approach would be to include eye protection in a well-­designed personal protective equipment program.

In the absence of aerosol-generating procedures, N95 respirators confer no additional benefit in preventing HCW respiratory infections when droplet transmission is suspected. However, the applicability of the available evidence is limited given the uncertainties surrounding SARS-CoV-2 transmission. When RPE may become scarce during a pandemic, the risk of potential self-contamination must be weighed against RPE conservation strategies. RPE compliance, herd-protection effects of routine RPE use, and RPE contamination from prolonged use are therefore important elements to consider when implementing hospital policies regarding universal masking because they all impact the potential effectiveness of RPE.

At the present time we lack definitive evidence on the effectiveness of surgical masks vs respirators and continuous vs targeted RPE use in the hospital setting for SARS-CoV-2. If our goal is to minimize risk of HCW infection, continuous use of N95 respirator could be considered. However, a more pragmatic solution in the setting of a limited supply of N95 respirators would be continuous use of surgical masks while engaged in clinical care of patients under investigation or with confirmed COVID-19.

One contentious issue during the COVID-19 crisis has been the appropriate selection and use of respiratory protective equipment (RPE) for healthcare workers (HCWs) in hospitals and long-term care settings. As of April 2020, discrepancies exist in the recommendations from health authorities such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Canadian Standards Association (CSA). The first of these recommends a surgical mask for routine care and a respirator for high-risk care such as aerosol-generating procedures, while the CDC recommends respirators for all aspects of patient care for these SARS-CoV-2–infected patients, and the CSA risk assessment tool would also result in selection of a respirator.^1-3

Given the contradictory guidance, we will discuss several important considerations for hospital leaders in the implementation of a healthcare respiratory protection program during the current pandemic, including a focused review of the empirical data on surgical mask vs face-fitted respirator (most commonly available in healthcare as N95 in North America), continuous use of the RPE throughout an entire shift vs targeted use when caring for patients, and key areas of uncertainty.

Surgical masks are traditionally used for protection against droplet transmission of respiratory infections, in which large droplets often fall to the ground within short distances; on the other hand, N95 respirators are used for much smaller airborne pathogens, which can remain suspended in the air for long periods of time. Although empiric studies have supported the superiority of respirators over surgical masks in simulated settings (frequently defined as a calculated concentration ratio outside vs inside the RPE), most clinical studies fail to demonstrate a difference in clinical outcomes such as the prevention of respiratory infection. For instance, an exposure study using saline aerosol to simulate viral particles showed that N95 respirators conferred up to 8 to 12 times greater protection against particulate penetration, compared with surgical masks.⁴ However, these advantages of respirators over surgical masks in carefully controlled laboratory studies do not seem to translate to decreased infection risk in real-world settings.

The effectiveness of N95 respirators vs surgical masks in preventing respiratory infections has been evaluated in a small number of clinical randomized, controlled trials (RCTs). We identified five systematic reviews and/or metanalyses published after 2010 and three RCTs published after 1990.^5-12 The RCTs used laboratory-confirmed respiratory virus or clinical infection in HCWs as a clinical outcome, but studies differed in the implementation of RPE use (ie, continuous or targeted use). In a systematic review and metanalysis, Long et al identified six RCTs (9,171 participants) and concluded that, with the exception of laboratory-confirmed bacterial colonization, N95 respirators did not reduce the rate of laboratory-­confirmed influenza, viral respiratory infections, or influenza-like illness among HCWs, compared with surgical masks.⁵ The authors noted risks of bias in these studies owing to the inability to blind and conceal allocation. In addition, the studies focused on infections that are known to transmit via droplet, such as influenza, so the results might not be applicable in the face of a new pandemic in which the important modes of transmission are not yet clear.

The evidence base evaluating continuous vs targeted use of RPE in healthcare settings is quite small. Continuous use refers to using the RPE during an entire shift, whereas targeted use involves using RPE only when caring for confirmed or suspected respiratory patients. In our literature review we identified only one RCT that included separate study arms for continuous and targeted N95 respirator use.¹³ The authors found a significantly lower rate of clinical respiratory illness among HCWs in the continuous-use group, compared with that in the targeted-use group. Limitations of the study included a relatively short follow-up of 4 weeks and uneven distribution of baseline characteristics, although the authors adjusted for these differences in their analysis. The study, however, did not compare continuous vs targeted use of surgical masks with regard to clinical outcomes. Based on the study results, we can only infer that continuous use of RPE, either surgical mask or N95 respirator, may provide additional benefit to HCWs vs targeted use only.

Given the lack of robust evidence informing continuous or targeted RPE use, we suggest some additional factors to guide decision making. In settings with high HCW compliance with universal RPE (above 50%), even noncompliant HCW are protected against clinical respiratory illness, which suggests a herd protective effect when universal RPE use is implemented, likely owing to the prevention of symptomatic or asymptomatic infectious spread among HCWs.¹⁴ It is important to note that the compliance rate may be limited by discomfort of prolonged wear of certain RPEs. One study reported that compliance rate is lower for continuous use (66%) than it is for targeted use (82%).¹³ Accumulated respiratory pathogen deposition on RPEs from an extended period of use that could result in self-­contamination to the wearer is a potential concern, although these risks must be balanced against the repeated donning and doffing required by targeted use. Pilot studies examining viral particles left on surgical masks after being worn for entire shifts (or as long as tolerated) found that there were significantly more viral particles detected after 6 hours of continuous wear, which may increase the risk of self-contamination.¹⁵

The current literature is applicable to infections that are known to spread via droplet contact, and this is a major limitation in generalizing the available evidence to the SARS-CoV-2 pandemic, in which debate persists regarding the exact mode of transmission. It is postulated that, even in infections traditionally considered to be spread by droplets, such as influenza, aerosol transmission may occur when HCWs are working in close proximity to the exposure source or when the droplet evaporates and becomes droplet nuclei. The United States National Academies of Science, Engineering, and Medicine expert consultation report, published in April 2020, concluded that current studies support the possibility of aerosolization of SARS-CoV-2 virus from normal breathing.¹⁶ As of April 2020, the WHO recommendation for SARS-CoV-2 is to use droplet contact precautions with a surgical mask for regular patient care and N95 respirator for aerosol-generating procedures.¹ Although we have not come across any studies specifically comparing the efficacy between surgical mask to N95 respirator protection while performing aerosol-generating procedures, a systematic review found that certain aerosol-generating procedures, such as endotracheal intubation and noninvasive ventilation, conferred a significantly higher risk of transmission of SARS-CoV-1 to HCWs in 2003.¹⁷ For the current crisis, the CDC is taking a cautious approach in which N95 respirators are recommended for HCWs caring for patients with confirmed or suspected SARS-CoV-2 infection if the supply chain is secure, with advice in place in times of RPE shortage, such as use of expired respirators, other types of equivalent respirators, or respirators not approved by the National Institute for Occupational Safety and Health, as well as optimization of administrative and engineering controls (eg, telemedicine, limiting patient and visitor numbers, physical barriers, optimizing ventilation systems).^2,18 This advice is unusual in terms of deviating from advising the most appropriate RPE, and we presume it reflects the present global supply problems.

RPEs are only one component of a necessary personal protective equipment ensemble. Although eye protection (goggles or face shields) is recommended by the WHO and CDC when caring for patients with SARS-CoV-2, there is considerable uncertainty regarding the incremental effectiveness of eye protection because such protection is usually worn in conjunction with RPE. A 2019 Cochrane review did not identify any good-quality studies that could inform judgments regarding the effectiveness of eye protective equipment,¹⁹ and a recent rapid review reporting on the efficacy of eye protection in primary care settings reached a similar conclusion.²⁰ A risk-based approach would be to include eye protection in a well-­designed personal protective equipment program.

In the absence of aerosol-generating procedures, N95 respirators confer no additional benefit in preventing HCW respiratory infections when droplet transmission is suspected. However, the applicability of the available evidence is limited given the uncertainties surrounding SARS-CoV-2 transmission. When RPE may become scarce during a pandemic, the risk of potential self-contamination must be weighed against RPE conservation strategies. RPE compliance, herd-protection effects of routine RPE use, and RPE contamination from prolonged use are therefore important elements to consider when implementing hospital policies regarding universal masking because they all impact the potential effectiveness of RPE.

At the present time we lack definitive evidence on the effectiveness of surgical masks vs respirators and continuous vs targeted RPE use in the hospital setting for SARS-CoV-2. If our goal is to minimize risk of HCW infection, continuous use of N95 respirator could be considered. However, a more pragmatic solution in the setting of a limited supply of N95 respirators would be continuous use of surgical masks while engaged in clinical care of patients under investigation or with confirmed COVID-19.

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.

Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.

Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.

“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.

A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.

“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.

Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).

“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.

The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.

mzoler@mdedge.com

SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.

When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.

Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.

Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.

“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.

A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.

“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.

Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).

“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.

The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.

mzoler@mdedge.com

SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.

When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.

Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.

Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.

“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.

A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.

“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.

Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).

“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.

The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.

mzoler@mdedge.com

SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.