COVID-19 Updates

As an Episcopal priest, Father Robert Pace of Fort Worth, TX, is used to putting others first and reaching out to help. So when the pulmonologist who helped him through his ordeal with COVID-19 asked if he would like to donate blood to help other patients, he did not hesitate.

“I said, ‘Absolutely,’” Pace, 53, recalls. He says the idea was ‘very appealing.’ ” During his ordeal with COVID-19 in March, he had spent 3 days in the hospital, isolated and on IV fluids and oxygen. He was short of breath, with a heartbeat more rapid than usual.

Now, fully recovered, his blood was a precious commodity, antibody-rich and potentially life-saving.

As researchers scramble to test drugs to fight COVID-19, others are turning to an age-old treatment. They’re collecting the blood of survivors and giving it to patients in the throes of a severe infection, a treatment known as convalescent plasma therapy.

Doctors say the treatment will probably serve as a bridge until other drugs and a vaccine become available.

Although the FDA considers the treatment investigational, in late March, it eased access to it. Patients can get it as part of a clinical trial or through an expanded access program overseen by hospitals or universities. A doctor can also request permission to use the treatment for a single patient.

“It is considered an emergent, compassionate need,” says John Burk, MD, a pulmonologist at Texas Health Harris Methodist Hospital, Fort Worth, who treated Pace. “It is a way to bring it to the bedside.” And the approval can happen quickly. Burk says he got one from the FDA just 20 minutes after requesting it for a severely ill patient.
 

How it works

The premise of how it works is “quite straightforward,” says Michael Joyner, MD, a professor of anesthesiology at the Mayo Clinic, Rochester, MN. “When someone is recovered and no longer symptomatic, you can harvest those antibodies from their blood and give them to someone else, and hopefully alter the course of their disease.” Joyner is the principal investigator for the FDA’s national Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19, with 1,000 sites already signed on.

Convalescent therapy has been used to fight many other viruses, including Ebola, severe acute respiratory syndrome (SARS), the “bird” flu, H1N1 flu, and during the 1918 flu pandemic. Joyner says the strongest evidence for it comes from the 1950s, when it was used to treat a rodent-borne illness called Argentine hemorrhagic fever. Using convalescent plasma therapy for this infection reduced the death rate from nearly 43% before the treatment became common in the late 1950s to about 3% after it was widely used, one report found.

Data about convalescent therapy specifically for COVID-19 is limited. Chinese researchers reported on five critically ill patients, all on mechanical ventilation, treated with convalescent plasma after they had received antiviral and anti-inflammatory medicines. Three could leave the hospital after 51-55 days, and two were in stable condition in the hospital 37 days after the transfusion.

In another study of 10 severely ill patients, symptoms went away or improved in all 10 within 1 to 3 days after the transfusion. Two of the three on ventilators were weaned off and put on oxygen instead. None died.

Chinese researchers also reported three cases of patients with COVID-19 given the convalescent therapy who had a satisfactory recovery.

Researchers who reviewed the track record of convalescent therapy for other conditions recently concluded that the treatment doesn’t appear to cause severe side effects and it should be studied for COVID-19.

Although information on side effects specific to this treatment is evolving, Joyner says they are “very, very low.”

According to the FDA, allergic reactions can occur with plasma therapies. Because the treatment for COVID-19 is new, it is not known if patients might have other types of reactions.
 

Who can donate?

Blood bank officials and researchers running the convalescent plasma programs say the desire to help is widespread, and they’ve been deluged with offers to donate. But requirements are strict.

Donors must have evidence of COVID-19 infection, documented in a variety of ways, such as a diagnostic test by nasal swab or a blood test showing antibodies. And they must be symptom-free for 14 days, with test results, or 28 days without.

The treatment involves collecting plasma, not whole blood. Plasma, the liquid part of the blood, helps with clotting and supports immunity. During the collection, a donor’s blood is put through a machine that collects the plasma only and sends the red blood cells and platelets back to the donor.
 

Clinical trials

Requirements may be more stringent for donors joining a formal clinical trial rather than an expanded access program. For instance, potential donors in a randomized clinical trial underway at Stony Brook University must have higher antibody levels than required by the FDA, says study leader Elliott Bennett-Guerrero, MD, medical director of perioperative quality and patient safety and professor at the Renaissance School of Medicine.

He hopes to enroll up to 500 patients from the Long Island, NY, area. While clinical trials typically have a 50-50 split, with half of subjects getting a treatment and half a placebo, Bennett-Guerrero’s study will give 80% of patients the convalescent plasma and 20% standard plasma.

Julia Sabia Motley, 57, of Merrick, NY, is hoping to become a donor for the Stony Brook study. She and her husband, Sean Motley, 59, tested positive in late March. She has to pass one more test to join the trial. Her husband is also planning to try to donate. “I can finally do something,” Sabia Motley says. Her son is in the MD-PhD program at Stony Brook and told her about the study.
 

Many questions remain

The treatment for COVID-19 is in its infancy. Burk has given the convalescent plasma to two patients. One is now recovering at home, and the other is on a ventilator but improving, he says.

About 200 nationwide have received the therapy, Joyner says. He expects blood supplies to increase as more people are eligible to donate.

Questions remain about how effective the convalescent therapy will be. While experts know that the COVID-19 antibodies “can be helpful in fighting the virus, we don’t know how long the antibodies in the plasma would stay in place,” Bennett-Guerrero says.

Nor do doctors know who the therapy might work best for, beyond people with a severe or life-threatening illness. When it’s been used for other infections, it’s generally given in early stages once someone has symptoms, Joyner says.

Joyner says he sees the treatment as a stopgap ‘’until concentrated antibodies are available.” Several drug companies are working to retrieve antibodies from donors and make concentrated antibody drugs.

“Typically we would think convalescent plasma might be a helpful bridge until therapies that are safe and effective and can be mass-produced are available, such as a vaccine or a drug,” Bennett-Guerrero says.

Even so, he says that he doesn’t think he will have a problem attracting donors, and that he will have repeat donors eager to help.
 

More information for potential donors

Blood banks, the American Red Cross, and others involved in convalescent plasma therapy have posted information online for potential donors. People who don’t meet the qualifications for COVID-19 plasma donations are welcomed as regular blood donors if they meet those criteria

According to the FDA, a donation could potentially help save the lives of up to four COVID-19 patients.

Father Pace is already planning another visit to the blood bank. To pass the time last time, he says, he prayed for the person who would eventually get his blood.

This article first appeared on WebMD.com.

As an Episcopal priest, Father Robert Pace of Fort Worth, TX, is used to putting others first and reaching out to help. So when the pulmonologist who helped him through his ordeal with COVID-19 asked if he would like to donate blood to help other patients, he did not hesitate.

“I said, ‘Absolutely,’” Pace, 53, recalls. He says the idea was ‘very appealing.’ ” During his ordeal with COVID-19 in March, he had spent 3 days in the hospital, isolated and on IV fluids and oxygen. He was short of breath, with a heartbeat more rapid than usual.

Now, fully recovered, his blood was a precious commodity, antibody-rich and potentially life-saving.

As researchers scramble to test drugs to fight COVID-19, others are turning to an age-old treatment. They’re collecting the blood of survivors and giving it to patients in the throes of a severe infection, a treatment known as convalescent plasma therapy.

Doctors say the treatment will probably serve as a bridge until other drugs and a vaccine become available.

Although the FDA considers the treatment investigational, in late March, it eased access to it. Patients can get it as part of a clinical trial or through an expanded access program overseen by hospitals or universities. A doctor can also request permission to use the treatment for a single patient.

“It is considered an emergent, compassionate need,” says John Burk, MD, a pulmonologist at Texas Health Harris Methodist Hospital, Fort Worth, who treated Pace. “It is a way to bring it to the bedside.” And the approval can happen quickly. Burk says he got one from the FDA just 20 minutes after requesting it for a severely ill patient.
 

How it works

The premise of how it works is “quite straightforward,” says Michael Joyner, MD, a professor of anesthesiology at the Mayo Clinic, Rochester, MN. “When someone is recovered and no longer symptomatic, you can harvest those antibodies from their blood and give them to someone else, and hopefully alter the course of their disease.” Joyner is the principal investigator for the FDA’s national Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19, with 1,000 sites already signed on.

Convalescent therapy has been used to fight many other viruses, including Ebola, severe acute respiratory syndrome (SARS), the “bird” flu, H1N1 flu, and during the 1918 flu pandemic. Joyner says the strongest evidence for it comes from the 1950s, when it was used to treat a rodent-borne illness called Argentine hemorrhagic fever. Using convalescent plasma therapy for this infection reduced the death rate from nearly 43% before the treatment became common in the late 1950s to about 3% after it was widely used, one report found.

Data about convalescent therapy specifically for COVID-19 is limited. Chinese researchers reported on five critically ill patients, all on mechanical ventilation, treated with convalescent plasma after they had received antiviral and anti-inflammatory medicines. Three could leave the hospital after 51-55 days, and two were in stable condition in the hospital 37 days after the transfusion.

In another study of 10 severely ill patients, symptoms went away or improved in all 10 within 1 to 3 days after the transfusion. Two of the three on ventilators were weaned off and put on oxygen instead. None died.

Chinese researchers also reported three cases of patients with COVID-19 given the convalescent therapy who had a satisfactory recovery.

Researchers who reviewed the track record of convalescent therapy for other conditions recently concluded that the treatment doesn’t appear to cause severe side effects and it should be studied for COVID-19.

Although information on side effects specific to this treatment is evolving, Joyner says they are “very, very low.”

According to the FDA, allergic reactions can occur with plasma therapies. Because the treatment for COVID-19 is new, it is not known if patients might have other types of reactions.
 

Who can donate?

Blood bank officials and researchers running the convalescent plasma programs say the desire to help is widespread, and they’ve been deluged with offers to donate. But requirements are strict.

Donors must have evidence of COVID-19 infection, documented in a variety of ways, such as a diagnostic test by nasal swab or a blood test showing antibodies. And they must be symptom-free for 14 days, with test results, or 28 days without.

The treatment involves collecting plasma, not whole blood. Plasma, the liquid part of the blood, helps with clotting and supports immunity. During the collection, a donor’s blood is put through a machine that collects the plasma only and sends the red blood cells and platelets back to the donor.
 

Clinical trials

Requirements may be more stringent for donors joining a formal clinical trial rather than an expanded access program. For instance, potential donors in a randomized clinical trial underway at Stony Brook University must have higher antibody levels than required by the FDA, says study leader Elliott Bennett-Guerrero, MD, medical director of perioperative quality and patient safety and professor at the Renaissance School of Medicine.

He hopes to enroll up to 500 patients from the Long Island, NY, area. While clinical trials typically have a 50-50 split, with half of subjects getting a treatment and half a placebo, Bennett-Guerrero’s study will give 80% of patients the convalescent plasma and 20% standard plasma.

Julia Sabia Motley, 57, of Merrick, NY, is hoping to become a donor for the Stony Brook study. She and her husband, Sean Motley, 59, tested positive in late March. She has to pass one more test to join the trial. Her husband is also planning to try to donate. “I can finally do something,” Sabia Motley says. Her son is in the MD-PhD program at Stony Brook and told her about the study.
 

Many questions remain

The treatment for COVID-19 is in its infancy. Burk has given the convalescent plasma to two patients. One is now recovering at home, and the other is on a ventilator but improving, he says.

About 200 nationwide have received the therapy, Joyner says. He expects blood supplies to increase as more people are eligible to donate.

Questions remain about how effective the convalescent therapy will be. While experts know that the COVID-19 antibodies “can be helpful in fighting the virus, we don’t know how long the antibodies in the plasma would stay in place,” Bennett-Guerrero says.

Nor do doctors know who the therapy might work best for, beyond people with a severe or life-threatening illness. When it’s been used for other infections, it’s generally given in early stages once someone has symptoms, Joyner says.

Joyner says he sees the treatment as a stopgap ‘’until concentrated antibodies are available.” Several drug companies are working to retrieve antibodies from donors and make concentrated antibody drugs.

“Typically we would think convalescent plasma might be a helpful bridge until therapies that are safe and effective and can be mass-produced are available, such as a vaccine or a drug,” Bennett-Guerrero says.

Even so, he says that he doesn’t think he will have a problem attracting donors, and that he will have repeat donors eager to help.
 

More information for potential donors

Blood banks, the American Red Cross, and others involved in convalescent plasma therapy have posted information online for potential donors. People who don’t meet the qualifications for COVID-19 plasma donations are welcomed as regular blood donors if they meet those criteria

According to the FDA, a donation could potentially help save the lives of up to four COVID-19 patients.

Father Pace is already planning another visit to the blood bank. To pass the time last time, he says, he prayed for the person who would eventually get his blood.

This article first appeared on WebMD.com.

As an Episcopal priest, Father Robert Pace of Fort Worth, TX, is used to putting others first and reaching out to help. So when the pulmonologist who helped him through his ordeal with COVID-19 asked if he would like to donate blood to help other patients, he did not hesitate.

“I said, ‘Absolutely,’” Pace, 53, recalls. He says the idea was ‘very appealing.’ ” During his ordeal with COVID-19 in March, he had spent 3 days in the hospital, isolated and on IV fluids and oxygen. He was short of breath, with a heartbeat more rapid than usual.

Now, fully recovered, his blood was a precious commodity, antibody-rich and potentially life-saving.

As researchers scramble to test drugs to fight COVID-19, others are turning to an age-old treatment. They’re collecting the blood of survivors and giving it to patients in the throes of a severe infection, a treatment known as convalescent plasma therapy.

Doctors say the treatment will probably serve as a bridge until other drugs and a vaccine become available.

Although the FDA considers the treatment investigational, in late March, it eased access to it. Patients can get it as part of a clinical trial or through an expanded access program overseen by hospitals or universities. A doctor can also request permission to use the treatment for a single patient.

“It is considered an emergent, compassionate need,” says John Burk, MD, a pulmonologist at Texas Health Harris Methodist Hospital, Fort Worth, who treated Pace. “It is a way to bring it to the bedside.” And the approval can happen quickly. Burk says he got one from the FDA just 20 minutes after requesting it for a severely ill patient.
 

How it works

The premise of how it works is “quite straightforward,” says Michael Joyner, MD, a professor of anesthesiology at the Mayo Clinic, Rochester, MN. “When someone is recovered and no longer symptomatic, you can harvest those antibodies from their blood and give them to someone else, and hopefully alter the course of their disease.” Joyner is the principal investigator for the FDA’s national Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19, with 1,000 sites already signed on.

Convalescent therapy has been used to fight many other viruses, including Ebola, severe acute respiratory syndrome (SARS), the “bird” flu, H1N1 flu, and during the 1918 flu pandemic. Joyner says the strongest evidence for it comes from the 1950s, when it was used to treat a rodent-borne illness called Argentine hemorrhagic fever. Using convalescent plasma therapy for this infection reduced the death rate from nearly 43% before the treatment became common in the late 1950s to about 3% after it was widely used, one report found.

Data about convalescent therapy specifically for COVID-19 is limited. Chinese researchers reported on five critically ill patients, all on mechanical ventilation, treated with convalescent plasma after they had received antiviral and anti-inflammatory medicines. Three could leave the hospital after 51-55 days, and two were in stable condition in the hospital 37 days after the transfusion.

In another study of 10 severely ill patients, symptoms went away or improved in all 10 within 1 to 3 days after the transfusion. Two of the three on ventilators were weaned off and put on oxygen instead. None died.

Chinese researchers also reported three cases of patients with COVID-19 given the convalescent therapy who had a satisfactory recovery.

Researchers who reviewed the track record of convalescent therapy for other conditions recently concluded that the treatment doesn’t appear to cause severe side effects and it should be studied for COVID-19.

Although information on side effects specific to this treatment is evolving, Joyner says they are “very, very low.”

According to the FDA, allergic reactions can occur with plasma therapies. Because the treatment for COVID-19 is new, it is not known if patients might have other types of reactions.
 

Who can donate?

Blood bank officials and researchers running the convalescent plasma programs say the desire to help is widespread, and they’ve been deluged with offers to donate. But requirements are strict.

Donors must have evidence of COVID-19 infection, documented in a variety of ways, such as a diagnostic test by nasal swab or a blood test showing antibodies. And they must be symptom-free for 14 days, with test results, or 28 days without.

The treatment involves collecting plasma, not whole blood. Plasma, the liquid part of the blood, helps with clotting and supports immunity. During the collection, a donor’s blood is put through a machine that collects the plasma only and sends the red blood cells and platelets back to the donor.
 

Clinical trials

Requirements may be more stringent for donors joining a formal clinical trial rather than an expanded access program. For instance, potential donors in a randomized clinical trial underway at Stony Brook University must have higher antibody levels than required by the FDA, says study leader Elliott Bennett-Guerrero, MD, medical director of perioperative quality and patient safety and professor at the Renaissance School of Medicine.

He hopes to enroll up to 500 patients from the Long Island, NY, area. While clinical trials typically have a 50-50 split, with half of subjects getting a treatment and half a placebo, Bennett-Guerrero’s study will give 80% of patients the convalescent plasma and 20% standard plasma.

Julia Sabia Motley, 57, of Merrick, NY, is hoping to become a donor for the Stony Brook study. She and her husband, Sean Motley, 59, tested positive in late March. She has to pass one more test to join the trial. Her husband is also planning to try to donate. “I can finally do something,” Sabia Motley says. Her son is in the MD-PhD program at Stony Brook and told her about the study.
 

Many questions remain

The treatment for COVID-19 is in its infancy. Burk has given the convalescent plasma to two patients. One is now recovering at home, and the other is on a ventilator but improving, he says.

About 200 nationwide have received the therapy, Joyner says. He expects blood supplies to increase as more people are eligible to donate.

Questions remain about how effective the convalescent therapy will be. While experts know that the COVID-19 antibodies “can be helpful in fighting the virus, we don’t know how long the antibodies in the plasma would stay in place,” Bennett-Guerrero says.

Nor do doctors know who the therapy might work best for, beyond people with a severe or life-threatening illness. When it’s been used for other infections, it’s generally given in early stages once someone has symptoms, Joyner says.

Joyner says he sees the treatment as a stopgap ‘’until concentrated antibodies are available.” Several drug companies are working to retrieve antibodies from donors and make concentrated antibody drugs.

“Typically we would think convalescent plasma might be a helpful bridge until therapies that are safe and effective and can be mass-produced are available, such as a vaccine or a drug,” Bennett-Guerrero says.

Even so, he says that he doesn’t think he will have a problem attracting donors, and that he will have repeat donors eager to help.
 

More information for potential donors

Blood banks, the American Red Cross, and others involved in convalescent plasma therapy have posted information online for potential donors. People who don’t meet the qualifications for COVID-19 plasma donations are welcomed as regular blood donors if they meet those criteria

According to the FDA, a donation could potentially help save the lives of up to four COVID-19 patients.

Father Pace is already planning another visit to the blood bank. To pass the time last time, he says, he prayed for the person who would eventually get his blood.

This article first appeared on WebMD.com.

The take-home message from a growing number of recent COVID-19 case reports is that the infection might be far more than a respiratory disease.

Although a cause-and-effect relationship is unknown, people with the virus have presented with or developed heart disease, acute liver injury, ongoing GI issues, skin manifestations, neurologic damage, and other problems, especially among sicker people.

For example, French physicians described an association with encephalopathy, agitation, confusion, and corticospinal tract signs among 58 people hospitalized with acute respiratory distress (N Engl J Med. 2020 Apr 15. doi: 10.1056/NEJMc2008597).

In particular, Yale New Haven (Conn.) Hospital is dealing with unexpected complications up close. Almost half of the beds there are occupied by COVID-19 patients. Over 100 people are in the ICU, and almost 70 intubated. Of the more than 750 COVID admissions so far, only about 350 have been discharged. “Even in a bad flu season, you never see something like this; it’s just unheard of,” said Harlan Krumholz, MD, a Yale cardiologist and professor of medicine helping lead the efforts there.
 

Kidney injuries prominent

“When they get to the ICU, we are seeing lots of people with acute kidney injuries; lots of people developing endocrine problems; people having blood sugar control issues, coagulation issues, blood clots. We are just waking up to the wide range of ways this virus can affect people. Our ignorance is profound,” Dr. Krumholz said, but physicians “recognize that this thing has the capability of attacking almost every single organ system, and it may or may not present with respiratory symptoms.”

It’s a similar story at Mt. Sinai South Nassau, a hospital in Oceanside, N.Y. “We’ve seen a lot of renal injury in people having complications, a lot of acute dialysis,” but it’s unclear how much is caused by the virus and how much is simply because people are so sick, said Aaron Glatt, MD, infectious disease professor and chair of medicine at the hospital. However, he said things are looking brighter than at Yale.

“We are not seeing the same level of increase in cases that we had previously, and we are starting to see extubations and discharges. We’ve treated a number of patients with plasma therapy, and hopefully that will be of benefit. We’ve seen some response to” the immunosuppressive “tocilizumab [Actemra], and a lot of response to very good respiratory therapy. I think we are starting to flatten the curve,” Dr. Glatt said.
 

“Look for tricky symptoms”

The growing awareness of COVID’s protean manifestations is evident in Medscape’s Consult forum, an online community where physicians and medical students share information and seek advice; there’s been over 200 COVID-19 cases and questions since January.

Early on, traffic was mostly about typical pulmonary presentations, but lately it’s shifted to nonrespiratory involvement. Physicians want to know if what they are seeing is related to the virus, and if other people are seeing the same things.

There’s a case on Consult of a 37-year-old man with stomach pain, vomiting, and diarrhea, but no respiratory symptoms and a positive COVID test. A chest CT incidental to his abdominal scan revealed significant bilateral lung involvement.

A 69-year-old woman with a history of laparotomy and new onset intestinal subocclusion had only adhesions on a subsequent exploratory laparotomy, and was doing okay otherwise. She suddenly went into respiratory failure with progressive bradycardia and died 3 days later. Aspiration pneumonia, pulmonary embolism, and MI had been ruled out. “The pattern of cardiovascular failure was in favor of myocarditis, but we don’t have any other clue,” the physician said after describing a second similar case.

Another doctor on the forum reported elevated cardiac enzymes without coronary artery obstruction in a positive patient who went into shock, with an ejection fraction of 40% and markedly increased heart wall thickness, but no lung involvement. There are also two cases of idiopathic thrombocytopenia without fever of hypoxia.

An Italian gastroenterologist said: “Look for tricky symptoms.” Expand “patient history, asking about the sudden occurrence of dysgeusia and/or anosmia. These symptoms have become my guiding diagnostic light” in Verona. “Most patients become nauseated, [and] the taste of any food is unbearable. When I find these symptoms by history, the patient is COVID positive 100%.”
 

‘Make sure that they didn’t die in vain’

There was interest in those and other reports on Consult, and comments from physicians who have theories, but no certain answers about what is, and is not, caused by the virus.

Direct viral attack is likely a part of it, said Stanley Perlman, MD, PhD, a professor of microbiology and immunology at the University of Iowa, Iowa City.

The ACE2 receptor the virus uses to enter cells is common in many organs, plus there were extrapulmonary manifestations with severe acute respiratory syndrome (SARS), another pandemic caused by a zoonotic coronavirus almost 20 years ago. At least with SARS, “many organs were infected when examined at autopsy,” he said.

The body’s inflammatory response is almost certainly also in play. Progressive derangements in inflammatory markers – C-reactive protein, D-dimer, ferritin – correlate with worse prognosis, and “the cytokine storm that occurs in these patients can lead to a degree of encephalopathy, myocarditis, liver impairment, and kidney impairment; multiorgan dysfunction, in other words,” said William Shaffner, MD, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

But in some cases, the virus might simply be a bystander to an unrelated disease process; in others, the experimental treatments being used might cause problems. Indeed, cardiology groups recently warned of torsade de pointes – a dangerously abnormal heart rhythm – with hydroxychloroquine and azithromycin.

“We think it’s some combination,” but don’t really know, Dr. Krumholz said. In the meantime, “we are forced to treat patients by instinct and first principles,” and long-term sequelae are unknown. “We don’t want to be in this position for long.”

To that end, he said, “this is the time for us all to hold hands and be together because we need to learn rapidly from each other. Our job is both to care for the people in front of us and make sure that they didn’t die in vain, that the experience they had is funneled into a larger set of data to make sure the next person is better off.”

aotto@mdedge.com

The take-home message from a growing number of recent COVID-19 case reports is that the infection might be far more than a respiratory disease.

Although a cause-and-effect relationship is unknown, people with the virus have presented with or developed heart disease, acute liver injury, ongoing GI issues, skin manifestations, neurologic damage, and other problems, especially among sicker people.

For example, French physicians described an association with encephalopathy, agitation, confusion, and corticospinal tract signs among 58 people hospitalized with acute respiratory distress (N Engl J Med. 2020 Apr 15. doi: 10.1056/NEJMc2008597).

In particular, Yale New Haven (Conn.) Hospital is dealing with unexpected complications up close. Almost half of the beds there are occupied by COVID-19 patients. Over 100 people are in the ICU, and almost 70 intubated. Of the more than 750 COVID admissions so far, only about 350 have been discharged. “Even in a bad flu season, you never see something like this; it’s just unheard of,” said Harlan Krumholz, MD, a Yale cardiologist and professor of medicine helping lead the efforts there.
 

Kidney injuries prominent

“When they get to the ICU, we are seeing lots of people with acute kidney injuries; lots of people developing endocrine problems; people having blood sugar control issues, coagulation issues, blood clots. We are just waking up to the wide range of ways this virus can affect people. Our ignorance is profound,” Dr. Krumholz said, but physicians “recognize that this thing has the capability of attacking almost every single organ system, and it may or may not present with respiratory symptoms.”

It’s a similar story at Mt. Sinai South Nassau, a hospital in Oceanside, N.Y. “We’ve seen a lot of renal injury in people having complications, a lot of acute dialysis,” but it’s unclear how much is caused by the virus and how much is simply because people are so sick, said Aaron Glatt, MD, infectious disease professor and chair of medicine at the hospital. However, he said things are looking brighter than at Yale.

“We are not seeing the same level of increase in cases that we had previously, and we are starting to see extubations and discharges. We’ve treated a number of patients with plasma therapy, and hopefully that will be of benefit. We’ve seen some response to” the immunosuppressive “tocilizumab [Actemra], and a lot of response to very good respiratory therapy. I think we are starting to flatten the curve,” Dr. Glatt said.
 

“Look for tricky symptoms”

The growing awareness of COVID’s protean manifestations is evident in Medscape’s Consult forum, an online community where physicians and medical students share information and seek advice; there’s been over 200 COVID-19 cases and questions since January.

Early on, traffic was mostly about typical pulmonary presentations, but lately it’s shifted to nonrespiratory involvement. Physicians want to know if what they are seeing is related to the virus, and if other people are seeing the same things.

There’s a case on Consult of a 37-year-old man with stomach pain, vomiting, and diarrhea, but no respiratory symptoms and a positive COVID test. A chest CT incidental to his abdominal scan revealed significant bilateral lung involvement.

A 69-year-old woman with a history of laparotomy and new onset intestinal subocclusion had only adhesions on a subsequent exploratory laparotomy, and was doing okay otherwise. She suddenly went into respiratory failure with progressive bradycardia and died 3 days later. Aspiration pneumonia, pulmonary embolism, and MI had been ruled out. “The pattern of cardiovascular failure was in favor of myocarditis, but we don’t have any other clue,” the physician said after describing a second similar case.

Another doctor on the forum reported elevated cardiac enzymes without coronary artery obstruction in a positive patient who went into shock, with an ejection fraction of 40% and markedly increased heart wall thickness, but no lung involvement. There are also two cases of idiopathic thrombocytopenia without fever of hypoxia.

An Italian gastroenterologist said: “Look for tricky symptoms.” Expand “patient history, asking about the sudden occurrence of dysgeusia and/or anosmia. These symptoms have become my guiding diagnostic light” in Verona. “Most patients become nauseated, [and] the taste of any food is unbearable. When I find these symptoms by history, the patient is COVID positive 100%.”
 

‘Make sure that they didn’t die in vain’

There was interest in those and other reports on Consult, and comments from physicians who have theories, but no certain answers about what is, and is not, caused by the virus.

Direct viral attack is likely a part of it, said Stanley Perlman, MD, PhD, a professor of microbiology and immunology at the University of Iowa, Iowa City.

The ACE2 receptor the virus uses to enter cells is common in many organs, plus there were extrapulmonary manifestations with severe acute respiratory syndrome (SARS), another pandemic caused by a zoonotic coronavirus almost 20 years ago. At least with SARS, “many organs were infected when examined at autopsy,” he said.

The body’s inflammatory response is almost certainly also in play. Progressive derangements in inflammatory markers – C-reactive protein, D-dimer, ferritin – correlate with worse prognosis, and “the cytokine storm that occurs in these patients can lead to a degree of encephalopathy, myocarditis, liver impairment, and kidney impairment; multiorgan dysfunction, in other words,” said William Shaffner, MD, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

But in some cases, the virus might simply be a bystander to an unrelated disease process; in others, the experimental treatments being used might cause problems. Indeed, cardiology groups recently warned of torsade de pointes – a dangerously abnormal heart rhythm – with hydroxychloroquine and azithromycin.

“We think it’s some combination,” but don’t really know, Dr. Krumholz said. In the meantime, “we are forced to treat patients by instinct and first principles,” and long-term sequelae are unknown. “We don’t want to be in this position for long.”

To that end, he said, “this is the time for us all to hold hands and be together because we need to learn rapidly from each other. Our job is both to care for the people in front of us and make sure that they didn’t die in vain, that the experience they had is funneled into a larger set of data to make sure the next person is better off.”

aotto@mdedge.com

The take-home message from a growing number of recent COVID-19 case reports is that the infection might be far more than a respiratory disease.

Although a cause-and-effect relationship is unknown, people with the virus have presented with or developed heart disease, acute liver injury, ongoing GI issues, skin manifestations, neurologic damage, and other problems, especially among sicker people.

For example, French physicians described an association with encephalopathy, agitation, confusion, and corticospinal tract signs among 58 people hospitalized with acute respiratory distress (N Engl J Med. 2020 Apr 15. doi: 10.1056/NEJMc2008597).

In particular, Yale New Haven (Conn.) Hospital is dealing with unexpected complications up close. Almost half of the beds there are occupied by COVID-19 patients. Over 100 people are in the ICU, and almost 70 intubated. Of the more than 750 COVID admissions so far, only about 350 have been discharged. “Even in a bad flu season, you never see something like this; it’s just unheard of,” said Harlan Krumholz, MD, a Yale cardiologist and professor of medicine helping lead the efforts there.
 

Kidney injuries prominent

“When they get to the ICU, we are seeing lots of people with acute kidney injuries; lots of people developing endocrine problems; people having blood sugar control issues, coagulation issues, blood clots. We are just waking up to the wide range of ways this virus can affect people. Our ignorance is profound,” Dr. Krumholz said, but physicians “recognize that this thing has the capability of attacking almost every single organ system, and it may or may not present with respiratory symptoms.”

It’s a similar story at Mt. Sinai South Nassau, a hospital in Oceanside, N.Y. “We’ve seen a lot of renal injury in people having complications, a lot of acute dialysis,” but it’s unclear how much is caused by the virus and how much is simply because people are so sick, said Aaron Glatt, MD, infectious disease professor and chair of medicine at the hospital. However, he said things are looking brighter than at Yale.

“We are not seeing the same level of increase in cases that we had previously, and we are starting to see extubations and discharges. We’ve treated a number of patients with plasma therapy, and hopefully that will be of benefit. We’ve seen some response to” the immunosuppressive “tocilizumab [Actemra], and a lot of response to very good respiratory therapy. I think we are starting to flatten the curve,” Dr. Glatt said.
 

“Look for tricky symptoms”

The growing awareness of COVID’s protean manifestations is evident in Medscape’s Consult forum, an online community where physicians and medical students share information and seek advice; there’s been over 200 COVID-19 cases and questions since January.

Early on, traffic was mostly about typical pulmonary presentations, but lately it’s shifted to nonrespiratory involvement. Physicians want to know if what they are seeing is related to the virus, and if other people are seeing the same things.

There’s a case on Consult of a 37-year-old man with stomach pain, vomiting, and diarrhea, but no respiratory symptoms and a positive COVID test. A chest CT incidental to his abdominal scan revealed significant bilateral lung involvement.

A 69-year-old woman with a history of laparotomy and new onset intestinal subocclusion had only adhesions on a subsequent exploratory laparotomy, and was doing okay otherwise. She suddenly went into respiratory failure with progressive bradycardia and died 3 days later. Aspiration pneumonia, pulmonary embolism, and MI had been ruled out. “The pattern of cardiovascular failure was in favor of myocarditis, but we don’t have any other clue,” the physician said after describing a second similar case.

Another doctor on the forum reported elevated cardiac enzymes without coronary artery obstruction in a positive patient who went into shock, with an ejection fraction of 40% and markedly increased heart wall thickness, but no lung involvement. There are also two cases of idiopathic thrombocytopenia without fever of hypoxia.

An Italian gastroenterologist said: “Look for tricky symptoms.” Expand “patient history, asking about the sudden occurrence of dysgeusia and/or anosmia. These symptoms have become my guiding diagnostic light” in Verona. “Most patients become nauseated, [and] the taste of any food is unbearable. When I find these symptoms by history, the patient is COVID positive 100%.”
 

‘Make sure that they didn’t die in vain’

There was interest in those and other reports on Consult, and comments from physicians who have theories, but no certain answers about what is, and is not, caused by the virus.

Direct viral attack is likely a part of it, said Stanley Perlman, MD, PhD, a professor of microbiology and immunology at the University of Iowa, Iowa City.

The ACE2 receptor the virus uses to enter cells is common in many organs, plus there were extrapulmonary manifestations with severe acute respiratory syndrome (SARS), another pandemic caused by a zoonotic coronavirus almost 20 years ago. At least with SARS, “many organs were infected when examined at autopsy,” he said.

The body’s inflammatory response is almost certainly also in play. Progressive derangements in inflammatory markers – C-reactive protein, D-dimer, ferritin – correlate with worse prognosis, and “the cytokine storm that occurs in these patients can lead to a degree of encephalopathy, myocarditis, liver impairment, and kidney impairment; multiorgan dysfunction, in other words,” said William Shaffner, MD, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

But in some cases, the virus might simply be a bystander to an unrelated disease process; in others, the experimental treatments being used might cause problems. Indeed, cardiology groups recently warned of torsade de pointes – a dangerously abnormal heart rhythm – with hydroxychloroquine and azithromycin.

“We think it’s some combination,” but don’t really know, Dr. Krumholz said. In the meantime, “we are forced to treat patients by instinct and first principles,” and long-term sequelae are unknown. “We don’t want to be in this position for long.”

To that end, he said, “this is the time for us all to hold hands and be together because we need to learn rapidly from each other. Our job is both to care for the people in front of us and make sure that they didn’t die in vain, that the experience they had is funneled into a larger set of data to make sure the next person is better off.”

aotto@mdedge.com

Two of the most unusual dermatologic drugs have resurged as possible first-line therapy for rescue treatment of hospitalized patients with SARS-CoV-2, despite extremely limited clinical data supporting their efficacy, optimal dose, treatment duration, and potential adverse effects.

Chloroquine and hydroxychloroquine were introduced as treatment and prophylaxis of malaria and approved by the Food and Drug Administration in 1949 and 1955, respectively. They belong to a class of drugs called 4-aminoquinolones and have a flat aromatic core and a basic side chain. The basic property of these drugs contribute to their ability to accumulate in lysosomes. They have a large volume of distribution in the blood and a half-life of 40-60 days. Important interactions include use with tamoxifen, proton pump inhibitors, and with smoking. Although both drugs cross the placenta, they don’t have any notable effects on the fetus.

Chloroquine and hydroxychloroquine enter the cell and accumulate in the lysosomes along a pH gradient. Within the lysosome, they increase the pH, thereby stabilizing lysosomes and inhibiting eosinophil and neutrophil chemotaxis and phagocytic activity. They also inhibit complement-mediated hemolysis, reduce acute phase reactants, and prevent MHC class II–mediated auto antigen presentation. Additionally, they decrease cell-mediated immunity by decreasing the production of interleukin-1 and plasma cell synthesis. Hydroxychloroquine can also accumulate in endosomes and inhibit toll-like receptor signaling, thereby reducing the production of proinflammatory cytokines.

One of the ways SARS-CoV-2 enters cells is by up-regulating and binding to ACE2. Chloroquine/hydroxychloroquine reduce glycosylation of ACE2 and thus inhibit viral entry. Additionally, by increasing the endosomal pH, they potentially inactivate enzymes that viruses require for replication. Their lifesaving benefits, however, are thought to involve blocking the proinflammatory cytokine IL-6 and suppressing the cytokine storm thought to induce acute respiratory distress syndrome. Interestingly, chloroquine has also been shown to allow zinc ions into the cell, and zinc is a potent inhibitor of coronavirus RNA polymerase.

Side effects of chloroquine and hydroxychloroquine include GI upset, retinal toxicity with long-term use, hypoglycemia, cardiomyopathy, QT prolongation, ventricular arrhythmias, and renal and liver toxicity. Adverse effects have been observed with long-term daily doses of more than 3.5 mg/kg of chloroquine or more than 6.5 mg/kg of hydroxychloroquine. Cutaneous effects include pruritus, morbilliform rashes (in an estimated 10% of those treated) and psoriasis flares, and blue-black hyperpigmentation (in about 25%) of the shins, face, oral palate, and nails.

Initial in vitro studies first showed evidence of the ability of chloroquine and hydroxychloroquine to inhibit SARS-CoV-2 viral activity. In February 2020, the first clinical results of 100 patients treated with chloroquine were reported in a news briefing by the Chinese government. On March 20, the first clinical trial was published offering guidelines for the treatment of COVID-19 using hydroxychloroquine and azithromycin combination therapy – albeit with many limitations and reported biases in the study. Despite the poorly designed studies and inconclusive evidence, on March 28, the FDA issued an Emergency Use Authorization that allows providers to request a supply of hydroxychloroquine or chloroquine for hospitalized patients with COVID-19 who are unable to join a clinical trial.

On April 2, the first clinical trial to evaluate the safety and efficacy of hydroxychloroquine in adults hospitalized with COVID-19 began at Vanderbilt University Medical Center, Nashville, Tenn. The ORCHID trial (Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease), funded by the National Heart, Lung, and Blood Institute. This blinded, placebo-controlled study is evaluating hydroxychloroquine treatment of hospitalized patients with COVID-19 in hopes of treating the severe complications of acute respiratory distress syndrome. Participants are randomly assigned to receive 400 mg hydroxychloroquine twice daily as a loading dose and then 200 mg twice daily thereafter on days 2-5. As of this writing, this study is currently underway and outcomes are expected in the upcoming weeks.

There is now a shortage of chloroquine and hydroxychloroquine in patients who have severe dermatologic and rheumatologic diseases, which include some who been in remission for years because of these medications and are in grave danger of recurrence. During this crisis, we desperately need well-controlled, randomized studies to test the efficacy and prolonged safety profile of these drugs in COVID-19 patients, as well as appropriate funding to source these medications for hospitalized and nonhospitalized patients in need.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at dermnews@mdedge.com.

Sources

Liu J et al. Cell Discov. 2020 Mar 18. doi: 10.1038/s41421-020-0156-0.

Vincent MJ et al. Virol J. 2005 Aug 22;2:69.

Gautret P et al. Int J Antimicrob Agents. 2020 Mar 20. doi: 10.1016/j.ijantimicag.2020.105949.

Devaux CA et al. Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

Aronson J et al. COVID-19 trials registered up to 8 March 2020 – an analysis of 382 studies. 2020. Centre for Evidence-Based Medicine. https://www.cebm.net/oxford-covid-19/covid-19-registered-trials-and-analysis/

Savarino A et al. Lancet Infect Dis. 2003 Nov;3(11):722-7.

Yazdany J, Kim AHJ. Ann Intern Med. 2020 Mar 31. doi: 10.7326/M20-1334.

Xue J et al. PLoS One. 2014 Oct 1;9(10):e109180.

te Velthuis AJ et al. PLoS Pathog. 2010 Nov 4;6(11):e1001176.

Two of the most unusual dermatologic drugs have resurged as possible first-line therapy for rescue treatment of hospitalized patients with SARS-CoV-2, despite extremely limited clinical data supporting their efficacy, optimal dose, treatment duration, and potential adverse effects.

Chloroquine and hydroxychloroquine were introduced as treatment and prophylaxis of malaria and approved by the Food and Drug Administration in 1949 and 1955, respectively. They belong to a class of drugs called 4-aminoquinolones and have a flat aromatic core and a basic side chain. The basic property of these drugs contribute to their ability to accumulate in lysosomes. They have a large volume of distribution in the blood and a half-life of 40-60 days. Important interactions include use with tamoxifen, proton pump inhibitors, and with smoking. Although both drugs cross the placenta, they don’t have any notable effects on the fetus.

Chloroquine and hydroxychloroquine enter the cell and accumulate in the lysosomes along a pH gradient. Within the lysosome, they increase the pH, thereby stabilizing lysosomes and inhibiting eosinophil and neutrophil chemotaxis and phagocytic activity. They also inhibit complement-mediated hemolysis, reduce acute phase reactants, and prevent MHC class II–mediated auto antigen presentation. Additionally, they decrease cell-mediated immunity by decreasing the production of interleukin-1 and plasma cell synthesis. Hydroxychloroquine can also accumulate in endosomes and inhibit toll-like receptor signaling, thereby reducing the production of proinflammatory cytokines.

One of the ways SARS-CoV-2 enters cells is by up-regulating and binding to ACE2. Chloroquine/hydroxychloroquine reduce glycosylation of ACE2 and thus inhibit viral entry. Additionally, by increasing the endosomal pH, they potentially inactivate enzymes that viruses require for replication. Their lifesaving benefits, however, are thought to involve blocking the proinflammatory cytokine IL-6 and suppressing the cytokine storm thought to induce acute respiratory distress syndrome. Interestingly, chloroquine has also been shown to allow zinc ions into the cell, and zinc is a potent inhibitor of coronavirus RNA polymerase.

Side effects of chloroquine and hydroxychloroquine include GI upset, retinal toxicity with long-term use, hypoglycemia, cardiomyopathy, QT prolongation, ventricular arrhythmias, and renal and liver toxicity. Adverse effects have been observed with long-term daily doses of more than 3.5 mg/kg of chloroquine or more than 6.5 mg/kg of hydroxychloroquine. Cutaneous effects include pruritus, morbilliform rashes (in an estimated 10% of those treated) and psoriasis flares, and blue-black hyperpigmentation (in about 25%) of the shins, face, oral palate, and nails.

Initial in vitro studies first showed evidence of the ability of chloroquine and hydroxychloroquine to inhibit SARS-CoV-2 viral activity. In February 2020, the first clinical results of 100 patients treated with chloroquine were reported in a news briefing by the Chinese government. On March 20, the first clinical trial was published offering guidelines for the treatment of COVID-19 using hydroxychloroquine and azithromycin combination therapy – albeit with many limitations and reported biases in the study. Despite the poorly designed studies and inconclusive evidence, on March 28, the FDA issued an Emergency Use Authorization that allows providers to request a supply of hydroxychloroquine or chloroquine for hospitalized patients with COVID-19 who are unable to join a clinical trial.

On April 2, the first clinical trial to evaluate the safety and efficacy of hydroxychloroquine in adults hospitalized with COVID-19 began at Vanderbilt University Medical Center, Nashville, Tenn. The ORCHID trial (Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease), funded by the National Heart, Lung, and Blood Institute. This blinded, placebo-controlled study is evaluating hydroxychloroquine treatment of hospitalized patients with COVID-19 in hopes of treating the severe complications of acute respiratory distress syndrome. Participants are randomly assigned to receive 400 mg hydroxychloroquine twice daily as a loading dose and then 200 mg twice daily thereafter on days 2-5. As of this writing, this study is currently underway and outcomes are expected in the upcoming weeks.

There is now a shortage of chloroquine and hydroxychloroquine in patients who have severe dermatologic and rheumatologic diseases, which include some who been in remission for years because of these medications and are in grave danger of recurrence. During this crisis, we desperately need well-controlled, randomized studies to test the efficacy and prolonged safety profile of these drugs in COVID-19 patients, as well as appropriate funding to source these medications for hospitalized and nonhospitalized patients in need.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at dermnews@mdedge.com.

Sources

Liu J et al. Cell Discov. 2020 Mar 18. doi: 10.1038/s41421-020-0156-0.

Vincent MJ et al. Virol J. 2005 Aug 22;2:69.

Gautret P et al. Int J Antimicrob Agents. 2020 Mar 20. doi: 10.1016/j.ijantimicag.2020.105949.

Devaux CA et al. Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

Aronson J et al. COVID-19 trials registered up to 8 March 2020 – an analysis of 382 studies. 2020. Centre for Evidence-Based Medicine. https://www.cebm.net/oxford-covid-19/covid-19-registered-trials-and-analysis/

Savarino A et al. Lancet Infect Dis. 2003 Nov;3(11):722-7.

Yazdany J, Kim AHJ. Ann Intern Med. 2020 Mar 31. doi: 10.7326/M20-1334.

Xue J et al. PLoS One. 2014 Oct 1;9(10):e109180.

te Velthuis AJ et al. PLoS Pathog. 2010 Nov 4;6(11):e1001176.

Two of the most unusual dermatologic drugs have resurged as possible first-line therapy for rescue treatment of hospitalized patients with SARS-CoV-2, despite extremely limited clinical data supporting their efficacy, optimal dose, treatment duration, and potential adverse effects.

Chloroquine and hydroxychloroquine were introduced as treatment and prophylaxis of malaria and approved by the Food and Drug Administration in 1949 and 1955, respectively. They belong to a class of drugs called 4-aminoquinolones and have a flat aromatic core and a basic side chain. The basic property of these drugs contribute to their ability to accumulate in lysosomes. They have a large volume of distribution in the blood and a half-life of 40-60 days. Important interactions include use with tamoxifen, proton pump inhibitors, and with smoking. Although both drugs cross the placenta, they don’t have any notable effects on the fetus.

Chloroquine and hydroxychloroquine enter the cell and accumulate in the lysosomes along a pH gradient. Within the lysosome, they increase the pH, thereby stabilizing lysosomes and inhibiting eosinophil and neutrophil chemotaxis and phagocytic activity. They also inhibit complement-mediated hemolysis, reduce acute phase reactants, and prevent MHC class II–mediated auto antigen presentation. Additionally, they decrease cell-mediated immunity by decreasing the production of interleukin-1 and plasma cell synthesis. Hydroxychloroquine can also accumulate in endosomes and inhibit toll-like receptor signaling, thereby reducing the production of proinflammatory cytokines.

One of the ways SARS-CoV-2 enters cells is by up-regulating and binding to ACE2. Chloroquine/hydroxychloroquine reduce glycosylation of ACE2 and thus inhibit viral entry. Additionally, by increasing the endosomal pH, they potentially inactivate enzymes that viruses require for replication. Their lifesaving benefits, however, are thought to involve blocking the proinflammatory cytokine IL-6 and suppressing the cytokine storm thought to induce acute respiratory distress syndrome. Interestingly, chloroquine has also been shown to allow zinc ions into the cell, and zinc is a potent inhibitor of coronavirus RNA polymerase.

Side effects of chloroquine and hydroxychloroquine include GI upset, retinal toxicity with long-term use, hypoglycemia, cardiomyopathy, QT prolongation, ventricular arrhythmias, and renal and liver toxicity. Adverse effects have been observed with long-term daily doses of more than 3.5 mg/kg of chloroquine or more than 6.5 mg/kg of hydroxychloroquine. Cutaneous effects include pruritus, morbilliform rashes (in an estimated 10% of those treated) and psoriasis flares, and blue-black hyperpigmentation (in about 25%) of the shins, face, oral palate, and nails.

Initial in vitro studies first showed evidence of the ability of chloroquine and hydroxychloroquine to inhibit SARS-CoV-2 viral activity. In February 2020, the first clinical results of 100 patients treated with chloroquine were reported in a news briefing by the Chinese government. On March 20, the first clinical trial was published offering guidelines for the treatment of COVID-19 using hydroxychloroquine and azithromycin combination therapy – albeit with many limitations and reported biases in the study. Despite the poorly designed studies and inconclusive evidence, on March 28, the FDA issued an Emergency Use Authorization that allows providers to request a supply of hydroxychloroquine or chloroquine for hospitalized patients with COVID-19 who are unable to join a clinical trial.

On April 2, the first clinical trial to evaluate the safety and efficacy of hydroxychloroquine in adults hospitalized with COVID-19 began at Vanderbilt University Medical Center, Nashville, Tenn. The ORCHID trial (Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease), funded by the National Heart, Lung, and Blood Institute. This blinded, placebo-controlled study is evaluating hydroxychloroquine treatment of hospitalized patients with COVID-19 in hopes of treating the severe complications of acute respiratory distress syndrome. Participants are randomly assigned to receive 400 mg hydroxychloroquine twice daily as a loading dose and then 200 mg twice daily thereafter on days 2-5. As of this writing, this study is currently underway and outcomes are expected in the upcoming weeks.

There is now a shortage of chloroquine and hydroxychloroquine in patients who have severe dermatologic and rheumatologic diseases, which include some who been in remission for years because of these medications and are in grave danger of recurrence. During this crisis, we desperately need well-controlled, randomized studies to test the efficacy and prolonged safety profile of these drugs in COVID-19 patients, as well as appropriate funding to source these medications for hospitalized and nonhospitalized patients in need.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at dermnews@mdedge.com.

Sources

Liu J et al. Cell Discov. 2020 Mar 18. doi: 10.1038/s41421-020-0156-0.

Vincent MJ et al. Virol J. 2005 Aug 22;2:69.

Gautret P et al. Int J Antimicrob Agents. 2020 Mar 20. doi: 10.1016/j.ijantimicag.2020.105949.

Devaux CA et al. Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.

Aronson J et al. COVID-19 trials registered up to 8 March 2020 – an analysis of 382 studies. 2020. Centre for Evidence-Based Medicine. https://www.cebm.net/oxford-covid-19/covid-19-registered-trials-and-analysis/

Savarino A et al. Lancet Infect Dis. 2003 Nov;3(11):722-7.

Yazdany J, Kim AHJ. Ann Intern Med. 2020 Mar 31. doi: 10.7326/M20-1334.

Xue J et al. PLoS One. 2014 Oct 1;9(10):e109180.

te Velthuis AJ et al. PLoS Pathog. 2010 Nov 4;6(11):e1001176.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the spread of COVID-19, is overwhelming for many people. Health care workers in the United States and around the world are leading the battle on the front lines of the pandemic. Thus, they experience a higher level of stress, fear, and anxiety during this crisis.

Over the course of weeks, hospitalists have reviewed articles, attended webinars, and discussed institutional strategies to respond to COVID-19. They follow the most up-to-date clinical information about the approach to patient care, conserving personal protective equipment (PPE), and guidance on how to talk to patients and families during crisis situations. The safety of hospitalists has been underscored with persistent advocacy from multiple organizations, for PPE, access to testing supplies, and decreasing any unnecessary exposure.

While it is agreed that the safety and well-being of hospital medicine teams is crucial to our society’s victory over COVID-19, very little has been discussed with regards to the “hospitalist” well-being and wellness during this pandemic.

The well-being of providers is essential to the success of a health care system. Many hospitalists already experience moral injury and showed evidence of provider burnout before COVID-19. With the onset of the pandemic, this will only get worse and burnout will accelerate if nothing is done to stop it. We cannot wait for the dust to settle to help our colleagues, we must act now.

Many providers have expressed similar pandemic fears, including, uncertainty about screening and testing capability, fear of the PPE shortage, fear of being exposed and underprepared, and fear of bringing the virus home and making family members sick. This list is not exclusive, and there are so many other factors that providers are internally processing, all while continuing their commitment to patient care and safety.

Practicing medicine comes with the heaviest of responsibilities, including the defense of the health of humanity. Therefore, it is easy to understand that, while providers are on the battlefield of this pandemic as they defend the health of humanity, they are not thinking of their own wellness or well-being. Moral injury describes the mental, emotional, and spiritual distress people feel after “perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.” This is already happening, with many hospitals in various cities running out of ventilators, lacking basic supplies for provider safety and leaving providers in survival mode on the front lines without their “suits of armor.” However, many providers will never recognize moral injury or burnout because they are focused on saving as many lives as possible with very limited resources.

While many websites can aid patient and community members on wellness during COVID-19, there is no specific forum or outlet for providers. We must give all hospital medicine team members a multimedia platform to address the fear, anxiety, and uncertainty of COVID-19. We must also provide them with techniques for resilience, coping strategies, and develop a network of support as the situation evolves, in real time.

We must remind hospitalists, “You may be scared, you may feel anxious, and that is okay. It is normal to have these feelings and it is healthy to acknowledge them. Fear serves as an important role in keeping us safe, but if left unchecked it can be horrifying and crippling. However, to conquer it we must face our fears together, with strategy, knowledge, and advocacy. This is the way to rebuild the current health care climate with confidence and trust.”

Although the world may seem foreign and dangerous, it is in adversity that we will find our strength as a hospital medicine community. We go to work every day because that is what we do. Your courage to come to work every day, in spite of any danger that it may present to you, is an inspiration to the world. The battle is not lost, and as individuals and as a community we must build resilience, inspire hope, and empower each other. We are stronger together than we are alone. As hospitalists around the country, and throughout the world, we must agree to uphold the moral integrity of medicine without sacrificing ourselves.
 

Dr. Williams is the vice-president of the Hampton Roads chapter of the Society of Hospital Medicine. She is a hospitalist at Sentara Careplex Hospital in Hampton, Va., where she also serves as the vice-president of the Medical Executive Committee.

Resource

Dean, Wendy; Talbot, Simon; and Dean, Austin. Reframing clinician distress: Moral injury not burnout. Fed Pract. 2019 Sept;36(9):400-2.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the spread of COVID-19, is overwhelming for many people. Health care workers in the United States and around the world are leading the battle on the front lines of the pandemic. Thus, they experience a higher level of stress, fear, and anxiety during this crisis.

Over the course of weeks, hospitalists have reviewed articles, attended webinars, and discussed institutional strategies to respond to COVID-19. They follow the most up-to-date clinical information about the approach to patient care, conserving personal protective equipment (PPE), and guidance on how to talk to patients and families during crisis situations. The safety of hospitalists has been underscored with persistent advocacy from multiple organizations, for PPE, access to testing supplies, and decreasing any unnecessary exposure.

While it is agreed that the safety and well-being of hospital medicine teams is crucial to our society’s victory over COVID-19, very little has been discussed with regards to the “hospitalist” well-being and wellness during this pandemic.

The well-being of providers is essential to the success of a health care system. Many hospitalists already experience moral injury and showed evidence of provider burnout before COVID-19. With the onset of the pandemic, this will only get worse and burnout will accelerate if nothing is done to stop it. We cannot wait for the dust to settle to help our colleagues, we must act now.

Many providers have expressed similar pandemic fears, including, uncertainty about screening and testing capability, fear of the PPE shortage, fear of being exposed and underprepared, and fear of bringing the virus home and making family members sick. This list is not exclusive, and there are so many other factors that providers are internally processing, all while continuing their commitment to patient care and safety.

Practicing medicine comes with the heaviest of responsibilities, including the defense of the health of humanity. Therefore, it is easy to understand that, while providers are on the battlefield of this pandemic as they defend the health of humanity, they are not thinking of their own wellness or well-being. Moral injury describes the mental, emotional, and spiritual distress people feel after “perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.” This is already happening, with many hospitals in various cities running out of ventilators, lacking basic supplies for provider safety and leaving providers in survival mode on the front lines without their “suits of armor.” However, many providers will never recognize moral injury or burnout because they are focused on saving as many lives as possible with very limited resources.

While many websites can aid patient and community members on wellness during COVID-19, there is no specific forum or outlet for providers. We must give all hospital medicine team members a multimedia platform to address the fear, anxiety, and uncertainty of COVID-19. We must also provide them with techniques for resilience, coping strategies, and develop a network of support as the situation evolves, in real time.

We must remind hospitalists, “You may be scared, you may feel anxious, and that is okay. It is normal to have these feelings and it is healthy to acknowledge them. Fear serves as an important role in keeping us safe, but if left unchecked it can be horrifying and crippling. However, to conquer it we must face our fears together, with strategy, knowledge, and advocacy. This is the way to rebuild the current health care climate with confidence and trust.”

Although the world may seem foreign and dangerous, it is in adversity that we will find our strength as a hospital medicine community. We go to work every day because that is what we do. Your courage to come to work every day, in spite of any danger that it may present to you, is an inspiration to the world. The battle is not lost, and as individuals and as a community we must build resilience, inspire hope, and empower each other. We are stronger together than we are alone. As hospitalists around the country, and throughout the world, we must agree to uphold the moral integrity of medicine without sacrificing ourselves.
 

Dr. Williams is the vice-president of the Hampton Roads chapter of the Society of Hospital Medicine. She is a hospitalist at Sentara Careplex Hospital in Hampton, Va., where she also serves as the vice-president of the Medical Executive Committee.

Resource

Dean, Wendy; Talbot, Simon; and Dean, Austin. Reframing clinician distress: Moral injury not burnout. Fed Pract. 2019 Sept;36(9):400-2.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the spread of COVID-19, is overwhelming for many people. Health care workers in the United States and around the world are leading the battle on the front lines of the pandemic. Thus, they experience a higher level of stress, fear, and anxiety during this crisis.

Over the course of weeks, hospitalists have reviewed articles, attended webinars, and discussed institutional strategies to respond to COVID-19. They follow the most up-to-date clinical information about the approach to patient care, conserving personal protective equipment (PPE), and guidance on how to talk to patients and families during crisis situations. The safety of hospitalists has been underscored with persistent advocacy from multiple organizations, for PPE, access to testing supplies, and decreasing any unnecessary exposure.

While it is agreed that the safety and well-being of hospital medicine teams is crucial to our society’s victory over COVID-19, very little has been discussed with regards to the “hospitalist” well-being and wellness during this pandemic.

The well-being of providers is essential to the success of a health care system. Many hospitalists already experience moral injury and showed evidence of provider burnout before COVID-19. With the onset of the pandemic, this will only get worse and burnout will accelerate if nothing is done to stop it. We cannot wait for the dust to settle to help our colleagues, we must act now.

Many providers have expressed similar pandemic fears, including, uncertainty about screening and testing capability, fear of the PPE shortage, fear of being exposed and underprepared, and fear of bringing the virus home and making family members sick. This list is not exclusive, and there are so many other factors that providers are internally processing, all while continuing their commitment to patient care and safety.

Practicing medicine comes with the heaviest of responsibilities, including the defense of the health of humanity. Therefore, it is easy to understand that, while providers are on the battlefield of this pandemic as they defend the health of humanity, they are not thinking of their own wellness or well-being. Moral injury describes the mental, emotional, and spiritual distress people feel after “perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.” This is already happening, with many hospitals in various cities running out of ventilators, lacking basic supplies for provider safety and leaving providers in survival mode on the front lines without their “suits of armor.” However, many providers will never recognize moral injury or burnout because they are focused on saving as many lives as possible with very limited resources.

While many websites can aid patient and community members on wellness during COVID-19, there is no specific forum or outlet for providers. We must give all hospital medicine team members a multimedia platform to address the fear, anxiety, and uncertainty of COVID-19. We must also provide them with techniques for resilience, coping strategies, and develop a network of support as the situation evolves, in real time.

We must remind hospitalists, “You may be scared, you may feel anxious, and that is okay. It is normal to have these feelings and it is healthy to acknowledge them. Fear serves as an important role in keeping us safe, but if left unchecked it can be horrifying and crippling. However, to conquer it we must face our fears together, with strategy, knowledge, and advocacy. This is the way to rebuild the current health care climate with confidence and trust.”

Although the world may seem foreign and dangerous, it is in adversity that we will find our strength as a hospital medicine community. We go to work every day because that is what we do. Your courage to come to work every day, in spite of any danger that it may present to you, is an inspiration to the world. The battle is not lost, and as individuals and as a community we must build resilience, inspire hope, and empower each other. We are stronger together than we are alone. As hospitalists around the country, and throughout the world, we must agree to uphold the moral integrity of medicine without sacrificing ourselves.
 

Dr. Williams is the vice-president of the Hampton Roads chapter of the Society of Hospital Medicine. She is a hospitalist at Sentara Careplex Hospital in Hampton, Va., where she also serves as the vice-president of the Medical Executive Committee.

Resource

Dean, Wendy; Talbot, Simon; and Dean, Austin. Reframing clinician distress: Moral injury not burnout. Fed Pract. 2019 Sept;36(9):400-2.

The SARS-CoV-2 novel coronavirus has dramatically altered specialty practice across the board, including the practice of infertility treatment. Reproductive medicine societies recommend suspending new infertility treatment cycles during this time. Women and couples who have already invested time and money in their treatment may be understandably frustrated and worried about the impact of this enforced – and indefinite – delay on their chances of conceiving. This puts the physician, who can’t even guarantee when treatment can resume, in the difficult position of trying to balance the patient’s needs with expert recommendations and government mandates.

Infertility Care During COVID-19

European and American reproductive medicine societies have both offered guidelines regarding infertility care during the pandemic. Both recommend shifting to the use of telehealth rather than in-person visits when possible for initial consultations and follow-up discussions.

With respect to infertility treatments during the COVID-19 pandemic, the American Society for Reproductive Medicine (ASRM) advises the following:

• Suspend initiation of new treatment cycles, including ovulation induction; intrauterine insemination; and in vitro fertilization, including retrievals and frozen embryo transfers, and suspend nonurgent gamete cryopreservation.
• Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
• Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
• Suspend elective surgeries and nonurgent diagnostic procedures.

In most countries, including the United States, all healthcare providers have been asked to put elective and nonurgent medical interventions on hold to ensure that personal protective equipment and other resources are available for the management of patients with COVID-19.

Infertility is a disease and, as such, not all infertility care should be considered elective. Still, for most patients, the overall chances of conceiving will not be compromised by a short delay (1-3 months) in treatment. A longer wait could have more impact on older patients or those who already have reduced ovarian reserve, but these are not indications for urgent fertility treatment.

There are clearly some cases in which infertility treatment cannot be delayed: for example, fertility preservation (oocyte or embryo vitrification) for patients who need to undergo immediate gonadotoxic oncology treatment. These patients need to be able to freeze oocytes/embryos so that later on, they have the option of having a family.

Another situation that could require new infertility treatment is a woman who needs urgent surgery for a condition such as severe symptomatic endometriosis causing ureteral or bowel stenosis/obstruction. Because the surgery itself can compromise fertility, the patient may elect to undergo oocyte embryo cryopreservation or ovarian tissue cryopreservation before the surgical procedure.
 

Pregnancy and COVID-19

As a precautionary measure during the COVID-19 pandemic, it is recommended that planned pregnancy be avoided. The available data on the risks presented by planning a pregnancy during the COVID pandemic are reassuring but limited.

Pregnancy itself has not been shown to alter the course of COVID-19, and most affected pregnant women will experience only mild or moderate flulike symptoms. Patients with cardiovascular or metabolic comorbidities or those requiring immunosuppressants are expected to be at increased risk for more severe forms of the infection. Currently, no strong evidence suggests a higher risk for miscarriage, stillbirth, or adverse neonatal outcomes with maternal COVID-19 infection.

A report based on 38 cases found no evidence for vertical transmission from mother to fetus, and all neonatal specimens (placental tissue) tested negative for the virus. Moreover, no maternal deaths were reported among these 38 infected women. Another study of 11 infected pregnant women likewise found no increased risk for perinatal morbidity or mortality.

On the other hand, a recent article on the perinatal outcomes of 33 neonates born to mothers with confirmed COVID-19 reported three cases of neonatal COVID-19 as a result of possible vertical transmission. In two cases, symptoms were mild and initial positive coronavirus test results turned negative within a few days. The third case – a pregnancy delivered by emergency cesarean section at 31 weeks for fetal distress – was complicated by bacterial sepsis, thrombocytopenia, and coagulopathy, but once again, the initially positive coronavirus test was negative by day 7.

No neonatal deaths were reported in these 33 cases. The authors could not rule out the possibility of vertical transmission in the three COVID-positive newborns because strict infection control measures were implemented during the care of the patients.
 

Counseling Patients About Suspending Infertility Treatments

Counseling women is the key to acceptance of the need to suspend or postpone infertility treatments during the pandemic. In addition to the economic hardships that some patients may face as a consequence of the pandemic, an obvious source of frustration stems from not knowing how long delays in treatment might be necessary. A discussion with patients or couples may reassure them that delaying conception is the safest route. For some women, other treatment options might be offered, such as the use of a donor gamete.

Some patients, even when counseled appropriately, may elect to accept the unknown risks. These patients should be counseled about the benefits of cryopreservation with delayed transfer. This could be a compromise, because their overall chances of pregnancy will not be affected but they will have to wait to become pregnant.

Counseling patients about the true impact of delaying treatment in their individual circumstances, providing them with emotional and (if needed) psychological support is important while they wait for their treatment to start. For now, the vast majority of the patients understand the need for delay, appreciate the opportunity to consult the physician over the phone, and are demonstrating patience as they wait for their treatment to start or resume.
 

Resuming Infertility Care

Recommendations could change as the pandemic continues and more information becomes available about the impact of coronavirus infection during pregnancy and the overall capacity of the healthcare system improves. ASRM acknowledges that “reproductive care professionals, in consultation with their patients, will have to consider reassessing the criteria of what represents urgent and non-urgent care.” If the data remain reassuring and social distancing measures are able to slow down the spread of the disease, the infertility care of those couples who would be most affected by a delay in their treatment could gradually be resumed. On April 14, ASRM updated its recommendations about resuming infertility treatment: “ While it is not yet prudent to resume nonemergency infertility procedures, the Task Force recognizes it is also time to begin to consider strategies and best practices for resuming time-sensitive fertility treatments in the face of COVID-19.”

It is likely that the return to “normal” daily practice will be done in a stepwise fashion. I expect the practices first to open for diagnostic infertility testing, then for the less invasive procedures (frozen embryo transfer, intrauterine insemination) and finally for the more invasive lengthy procedures (stimulation with retrieval and embryo transfer). During the reopening of practice, strict infection control measures will need to be observed.

Dr. Kovacs is the medical director of Kaali Institute IVF Center in Budapest, Hungary. He has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The SARS-CoV-2 novel coronavirus has dramatically altered specialty practice across the board, including the practice of infertility treatment. Reproductive medicine societies recommend suspending new infertility treatment cycles during this time. Women and couples who have already invested time and money in their treatment may be understandably frustrated and worried about the impact of this enforced – and indefinite – delay on their chances of conceiving. This puts the physician, who can’t even guarantee when treatment can resume, in the difficult position of trying to balance the patient’s needs with expert recommendations and government mandates.

Infertility Care During COVID-19

European and American reproductive medicine societies have both offered guidelines regarding infertility care during the pandemic. Both recommend shifting to the use of telehealth rather than in-person visits when possible for initial consultations and follow-up discussions.

With respect to infertility treatments during the COVID-19 pandemic, the American Society for Reproductive Medicine (ASRM) advises the following:

• Suspend initiation of new treatment cycles, including ovulation induction; intrauterine insemination; and in vitro fertilization, including retrievals and frozen embryo transfers, and suspend nonurgent gamete cryopreservation.
• Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
• Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
• Suspend elective surgeries and nonurgent diagnostic procedures.

In most countries, including the United States, all healthcare providers have been asked to put elective and nonurgent medical interventions on hold to ensure that personal protective equipment and other resources are available for the management of patients with COVID-19.

Infertility is a disease and, as such, not all infertility care should be considered elective. Still, for most patients, the overall chances of conceiving will not be compromised by a short delay (1-3 months) in treatment. A longer wait could have more impact on older patients or those who already have reduced ovarian reserve, but these are not indications for urgent fertility treatment.

There are clearly some cases in which infertility treatment cannot be delayed: for example, fertility preservation (oocyte or embryo vitrification) for patients who need to undergo immediate gonadotoxic oncology treatment. These patients need to be able to freeze oocytes/embryos so that later on, they have the option of having a family.

Another situation that could require new infertility treatment is a woman who needs urgent surgery for a condition such as severe symptomatic endometriosis causing ureteral or bowel stenosis/obstruction. Because the surgery itself can compromise fertility, the patient may elect to undergo oocyte embryo cryopreservation or ovarian tissue cryopreservation before the surgical procedure.
 

Pregnancy and COVID-19

As a precautionary measure during the COVID-19 pandemic, it is recommended that planned pregnancy be avoided. The available data on the risks presented by planning a pregnancy during the COVID pandemic are reassuring but limited.

Pregnancy itself has not been shown to alter the course of COVID-19, and most affected pregnant women will experience only mild or moderate flulike symptoms. Patients with cardiovascular or metabolic comorbidities or those requiring immunosuppressants are expected to be at increased risk for more severe forms of the infection. Currently, no strong evidence suggests a higher risk for miscarriage, stillbirth, or adverse neonatal outcomes with maternal COVID-19 infection.

A report based on 38 cases found no evidence for vertical transmission from mother to fetus, and all neonatal specimens (placental tissue) tested negative for the virus. Moreover, no maternal deaths were reported among these 38 infected women. Another study of 11 infected pregnant women likewise found no increased risk for perinatal morbidity or mortality.

On the other hand, a recent article on the perinatal outcomes of 33 neonates born to mothers with confirmed COVID-19 reported three cases of neonatal COVID-19 as a result of possible vertical transmission. In two cases, symptoms were mild and initial positive coronavirus test results turned negative within a few days. The third case – a pregnancy delivered by emergency cesarean section at 31 weeks for fetal distress – was complicated by bacterial sepsis, thrombocytopenia, and coagulopathy, but once again, the initially positive coronavirus test was negative by day 7.

No neonatal deaths were reported in these 33 cases. The authors could not rule out the possibility of vertical transmission in the three COVID-positive newborns because strict infection control measures were implemented during the care of the patients.
 

Counseling Patients About Suspending Infertility Treatments

Counseling women is the key to acceptance of the need to suspend or postpone infertility treatments during the pandemic. In addition to the economic hardships that some patients may face as a consequence of the pandemic, an obvious source of frustration stems from not knowing how long delays in treatment might be necessary. A discussion with patients or couples may reassure them that delaying conception is the safest route. For some women, other treatment options might be offered, such as the use of a donor gamete.

Some patients, even when counseled appropriately, may elect to accept the unknown risks. These patients should be counseled about the benefits of cryopreservation with delayed transfer. This could be a compromise, because their overall chances of pregnancy will not be affected but they will have to wait to become pregnant.

Counseling patients about the true impact of delaying treatment in their individual circumstances, providing them with emotional and (if needed) psychological support is important while they wait for their treatment to start. For now, the vast majority of the patients understand the need for delay, appreciate the opportunity to consult the physician over the phone, and are demonstrating patience as they wait for their treatment to start or resume.
 

Resuming Infertility Care

Recommendations could change as the pandemic continues and more information becomes available about the impact of coronavirus infection during pregnancy and the overall capacity of the healthcare system improves. ASRM acknowledges that “reproductive care professionals, in consultation with their patients, will have to consider reassessing the criteria of what represents urgent and non-urgent care.” If the data remain reassuring and social distancing measures are able to slow down the spread of the disease, the infertility care of those couples who would be most affected by a delay in their treatment could gradually be resumed. On April 14, ASRM updated its recommendations about resuming infertility treatment: “ While it is not yet prudent to resume nonemergency infertility procedures, the Task Force recognizes it is also time to begin to consider strategies and best practices for resuming time-sensitive fertility treatments in the face of COVID-19.”

It is likely that the return to “normal” daily practice will be done in a stepwise fashion. I expect the practices first to open for diagnostic infertility testing, then for the less invasive procedures (frozen embryo transfer, intrauterine insemination) and finally for the more invasive lengthy procedures (stimulation with retrieval and embryo transfer). During the reopening of practice, strict infection control measures will need to be observed.

Dr. Kovacs is the medical director of Kaali Institute IVF Center in Budapest, Hungary. He has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The SARS-CoV-2 novel coronavirus has dramatically altered specialty practice across the board, including the practice of infertility treatment. Reproductive medicine societies recommend suspending new infertility treatment cycles during this time. Women and couples who have already invested time and money in their treatment may be understandably frustrated and worried about the impact of this enforced – and indefinite – delay on their chances of conceiving. This puts the physician, who can’t even guarantee when treatment can resume, in the difficult position of trying to balance the patient’s needs with expert recommendations and government mandates.

Infertility Care During COVID-19

European and American reproductive medicine societies have both offered guidelines regarding infertility care during the pandemic. Both recommend shifting to the use of telehealth rather than in-person visits when possible for initial consultations and follow-up discussions.

With respect to infertility treatments during the COVID-19 pandemic, the American Society for Reproductive Medicine (ASRM) advises the following:

• Suspend initiation of new treatment cycles, including ovulation induction; intrauterine insemination; and in vitro fertilization, including retrievals and frozen embryo transfers, and suspend nonurgent gamete cryopreservation.
• Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
• Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
• Suspend elective surgeries and nonurgent diagnostic procedures.

In most countries, including the United States, all healthcare providers have been asked to put elective and nonurgent medical interventions on hold to ensure that personal protective equipment and other resources are available for the management of patients with COVID-19.

Infertility is a disease and, as such, not all infertility care should be considered elective. Still, for most patients, the overall chances of conceiving will not be compromised by a short delay (1-3 months) in treatment. A longer wait could have more impact on older patients or those who already have reduced ovarian reserve, but these are not indications for urgent fertility treatment.

There are clearly some cases in which infertility treatment cannot be delayed: for example, fertility preservation (oocyte or embryo vitrification) for patients who need to undergo immediate gonadotoxic oncology treatment. These patients need to be able to freeze oocytes/embryos so that later on, they have the option of having a family.

Another situation that could require new infertility treatment is a woman who needs urgent surgery for a condition such as severe symptomatic endometriosis causing ureteral or bowel stenosis/obstruction. Because the surgery itself can compromise fertility, the patient may elect to undergo oocyte embryo cryopreservation or ovarian tissue cryopreservation before the surgical procedure.
 

Pregnancy and COVID-19

As a precautionary measure during the COVID-19 pandemic, it is recommended that planned pregnancy be avoided. The available data on the risks presented by planning a pregnancy during the COVID pandemic are reassuring but limited.

Pregnancy itself has not been shown to alter the course of COVID-19, and most affected pregnant women will experience only mild or moderate flulike symptoms. Patients with cardiovascular or metabolic comorbidities or those requiring immunosuppressants are expected to be at increased risk for more severe forms of the infection. Currently, no strong evidence suggests a higher risk for miscarriage, stillbirth, or adverse neonatal outcomes with maternal COVID-19 infection.

A report based on 38 cases found no evidence for vertical transmission from mother to fetus, and all neonatal specimens (placental tissue) tested negative for the virus. Moreover, no maternal deaths were reported among these 38 infected women. Another study of 11 infected pregnant women likewise found no increased risk for perinatal morbidity or mortality.

On the other hand, a recent article on the perinatal outcomes of 33 neonates born to mothers with confirmed COVID-19 reported three cases of neonatal COVID-19 as a result of possible vertical transmission. In two cases, symptoms were mild and initial positive coronavirus test results turned negative within a few days. The third case – a pregnancy delivered by emergency cesarean section at 31 weeks for fetal distress – was complicated by bacterial sepsis, thrombocytopenia, and coagulopathy, but once again, the initially positive coronavirus test was negative by day 7.

No neonatal deaths were reported in these 33 cases. The authors could not rule out the possibility of vertical transmission in the three COVID-positive newborns because strict infection control measures were implemented during the care of the patients.
 

Counseling Patients About Suspending Infertility Treatments

Counseling women is the key to acceptance of the need to suspend or postpone infertility treatments during the pandemic. In addition to the economic hardships that some patients may face as a consequence of the pandemic, an obvious source of frustration stems from not knowing how long delays in treatment might be necessary. A discussion with patients or couples may reassure them that delaying conception is the safest route. For some women, other treatment options might be offered, such as the use of a donor gamete.

Some patients, even when counseled appropriately, may elect to accept the unknown risks. These patients should be counseled about the benefits of cryopreservation with delayed transfer. This could be a compromise, because their overall chances of pregnancy will not be affected but they will have to wait to become pregnant.

Counseling patients about the true impact of delaying treatment in their individual circumstances, providing them with emotional and (if needed) psychological support is important while they wait for their treatment to start. For now, the vast majority of the patients understand the need for delay, appreciate the opportunity to consult the physician over the phone, and are demonstrating patience as they wait for their treatment to start or resume.
 

Resuming Infertility Care

Recommendations could change as the pandemic continues and more information becomes available about the impact of coronavirus infection during pregnancy and the overall capacity of the healthcare system improves. ASRM acknowledges that “reproductive care professionals, in consultation with their patients, will have to consider reassessing the criteria of what represents urgent and non-urgent care.” If the data remain reassuring and social distancing measures are able to slow down the spread of the disease, the infertility care of those couples who would be most affected by a delay in their treatment could gradually be resumed. On April 14, ASRM updated its recommendations about resuming infertility treatment: “ While it is not yet prudent to resume nonemergency infertility procedures, the Task Force recognizes it is also time to begin to consider strategies and best practices for resuming time-sensitive fertility treatments in the face of COVID-19.”

It is likely that the return to “normal” daily practice will be done in a stepwise fashion. I expect the practices first to open for diagnostic infertility testing, then for the less invasive procedures (frozen embryo transfer, intrauterine insemination) and finally for the more invasive lengthy procedures (stimulation with retrieval and embryo transfer). During the reopening of practice, strict infection control measures will need to be observed.

Dr. Kovacs is the medical director of Kaali Institute IVF Center in Budapest, Hungary. He has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

There will be some change for the better when oncology care emerges from the COVID-19 pandemic, the most “revolutionary” being a deep dive into telehealth, predicts Deborah Schrag, MD, MPH, a medical oncologist specializing in gastrointestinal cancers at the Dana Farber Cancer Institute in Boston, Massachusetts.

“In the space of a month, approaches and accepted norms of cancer care delivery have been transformed of necessity,” Schrag and colleagues write in an article published in JAMA on April 13.

“Most of these changes would not have occurred without the pandemic,” they add. They predict that some changes will last after the crisis is over.

“None of us want to be thrown in the deep end.... On the other hand, sometimes it works,” Schrag told Medscape Medical News.

“The in-person visit between patient and physician has been upended,” she said.

“I don’t think there’s any going back to the way it was before because cancer patients won’t stand for it,” she said. “They’re not going to drive in to get the results of a blood test.

“I think that on balance, of course, there are situations where you need eye-to-eye contact. No one wants to have an initial oncology meeting by telehealth – doctors or patients – that’s ridiculous,” she said. “But for follow-up visits, patients are now going to be more demanding, and doctors will be more willing.”

The “essential empathy” of oncologists can still “transcend the new physical barriers presented by masks and telehealth,” Schrag and colleagues comment.

“Doctors are figuring out how to deliver empathy by Zoom,” she told Medscape Medical News. “It’s not the same, but we all convey empathy to our elderly relatives over the phone.”

Pandemic impact on oncology

While the crisis has affected all of medicine – dismantling how care is delivered and forcing clinicians to make difficult decisions regarding triage – the fact that some cancers present an immediate threat to survival means that oncology “provides a lens into the major shifts currently underway in clinical care,” Schrag and colleagues write.

They illustrate the point by highlighting systemic chemotherapy, which is provided to a large proportion of patients with advanced cancer. The pandemic has tipped the risk-benefit ratio away from treatments that have a marginal effect on quality or quantity of life, they note. It has forced an “elimination of low-value treatments that were identified by the Choosing Wisely campaign,” the authors write. Up to now, the uptake of recommendations to eliminate these treatments has been slow.

“For example, for most metastatic solid tumors, chemotherapy beyond the third regimen does not improve survival for more than a few weeks; therefore, oncologists are advising supportive care instead. For patients receiving adjuvant therapy for curable cancers, delaying initiation or abbreviating the number of cycles is appropriate. Oncologists are postponing initiation of adjuvant chemotherapy for some estrogen receptor–negative stage II breast cancers by 8 weeks and administering 6 rather than 12 cycles of adjuvant chemotherapy for stage III colorectal cancers,” Schrag and colleagues write.

On the other hand, even in the epicenters of the pandemic, thus far, oncologists are still delivering cancer treatments that have the potential to cure and cannot safely be delayed, they point out. “This includes most patients with new diagnoses of acute leukemia, high-grade lymphoma, and those with chemotherapy-responsive tumors such as testicular, ovarian, and small cell lung cancer. Despite the risks, oncologists are not modifying such treatments because these cancers are likely more lethal than COVID-19.”

It’s the cancer patients who fall in between these two extremes who pose the biggest treatment challenge during this crisis – the patients for whom a delay would have “moderate clinically important adverse influence on quality of life or survival.” In these cases, oncologists are “prescribing marginally less effective regimens that have lower risk of precipitating hospitalization,” the authors note.

These treatments include the use of “white cell growth factor, more stringent neutrophil counts for proceeding with a next cycle of therapy, and omitting use of steroids to manage nausea.” In addition, where possible, oncologists are substituting oral agents for intravenous agents and “myriad other modifications to minimize visits and hospitalizations.”

Most hospitals and outpatient infusion centers now prohibit visitors from accompanying patients, and oncologists are prioritizing conversations with patients about advance directives, healthcare proxies, and end-of-life care preferences. Yet, even here, telehealth offers a new, enhanced layer to those conversations by enabling families to gather with their loved one and the doctor, she said.

This article first appeared on Medscape.com.

There will be some change for the better when oncology care emerges from the COVID-19 pandemic, the most “revolutionary” being a deep dive into telehealth, predicts Deborah Schrag, MD, MPH, a medical oncologist specializing in gastrointestinal cancers at the Dana Farber Cancer Institute in Boston, Massachusetts.

“In the space of a month, approaches and accepted norms of cancer care delivery have been transformed of necessity,” Schrag and colleagues write in an article published in JAMA on April 13.

“Most of these changes would not have occurred without the pandemic,” they add. They predict that some changes will last after the crisis is over.

“None of us want to be thrown in the deep end.... On the other hand, sometimes it works,” Schrag told Medscape Medical News.

“The in-person visit between patient and physician has been upended,” she said.

“I don’t think there’s any going back to the way it was before because cancer patients won’t stand for it,” she said. “They’re not going to drive in to get the results of a blood test.

“I think that on balance, of course, there are situations where you need eye-to-eye contact. No one wants to have an initial oncology meeting by telehealth – doctors or patients – that’s ridiculous,” she said. “But for follow-up visits, patients are now going to be more demanding, and doctors will be more willing.”

The “essential empathy” of oncologists can still “transcend the new physical barriers presented by masks and telehealth,” Schrag and colleagues comment.

“Doctors are figuring out how to deliver empathy by Zoom,” she told Medscape Medical News. “It’s not the same, but we all convey empathy to our elderly relatives over the phone.”

Pandemic impact on oncology

While the crisis has affected all of medicine – dismantling how care is delivered and forcing clinicians to make difficult decisions regarding triage – the fact that some cancers present an immediate threat to survival means that oncology “provides a lens into the major shifts currently underway in clinical care,” Schrag and colleagues write.

They illustrate the point by highlighting systemic chemotherapy, which is provided to a large proportion of patients with advanced cancer. The pandemic has tipped the risk-benefit ratio away from treatments that have a marginal effect on quality or quantity of life, they note. It has forced an “elimination of low-value treatments that were identified by the Choosing Wisely campaign,” the authors write. Up to now, the uptake of recommendations to eliminate these treatments has been slow.

“For example, for most metastatic solid tumors, chemotherapy beyond the third regimen does not improve survival for more than a few weeks; therefore, oncologists are advising supportive care instead. For patients receiving adjuvant therapy for curable cancers, delaying initiation or abbreviating the number of cycles is appropriate. Oncologists are postponing initiation of adjuvant chemotherapy for some estrogen receptor–negative stage II breast cancers by 8 weeks and administering 6 rather than 12 cycles of adjuvant chemotherapy for stage III colorectal cancers,” Schrag and colleagues write.

On the other hand, even in the epicenters of the pandemic, thus far, oncologists are still delivering cancer treatments that have the potential to cure and cannot safely be delayed, they point out. “This includes most patients with new diagnoses of acute leukemia, high-grade lymphoma, and those with chemotherapy-responsive tumors such as testicular, ovarian, and small cell lung cancer. Despite the risks, oncologists are not modifying such treatments because these cancers are likely more lethal than COVID-19.”

It’s the cancer patients who fall in between these two extremes who pose the biggest treatment challenge during this crisis – the patients for whom a delay would have “moderate clinically important adverse influence on quality of life or survival.” In these cases, oncologists are “prescribing marginally less effective regimens that have lower risk of precipitating hospitalization,” the authors note.

These treatments include the use of “white cell growth factor, more stringent neutrophil counts for proceeding with a next cycle of therapy, and omitting use of steroids to manage nausea.” In addition, where possible, oncologists are substituting oral agents for intravenous agents and “myriad other modifications to minimize visits and hospitalizations.”

Most hospitals and outpatient infusion centers now prohibit visitors from accompanying patients, and oncologists are prioritizing conversations with patients about advance directives, healthcare proxies, and end-of-life care preferences. Yet, even here, telehealth offers a new, enhanced layer to those conversations by enabling families to gather with their loved one and the doctor, she said.

This article first appeared on Medscape.com.

There will be some change for the better when oncology care emerges from the COVID-19 pandemic, the most “revolutionary” being a deep dive into telehealth, predicts Deborah Schrag, MD, MPH, a medical oncologist specializing in gastrointestinal cancers at the Dana Farber Cancer Institute in Boston, Massachusetts.

“In the space of a month, approaches and accepted norms of cancer care delivery have been transformed of necessity,” Schrag and colleagues write in an article published in JAMA on April 13.

“Most of these changes would not have occurred without the pandemic,” they add. They predict that some changes will last after the crisis is over.

“None of us want to be thrown in the deep end.... On the other hand, sometimes it works,” Schrag told Medscape Medical News.

“The in-person visit between patient and physician has been upended,” she said.

“I don’t think there’s any going back to the way it was before because cancer patients won’t stand for it,” she said. “They’re not going to drive in to get the results of a blood test.

“I think that on balance, of course, there are situations where you need eye-to-eye contact. No one wants to have an initial oncology meeting by telehealth – doctors or patients – that’s ridiculous,” she said. “But for follow-up visits, patients are now going to be more demanding, and doctors will be more willing.”

The “essential empathy” of oncologists can still “transcend the new physical barriers presented by masks and telehealth,” Schrag and colleagues comment.

“Doctors are figuring out how to deliver empathy by Zoom,” she told Medscape Medical News. “It’s not the same, but we all convey empathy to our elderly relatives over the phone.”

Pandemic impact on oncology

While the crisis has affected all of medicine – dismantling how care is delivered and forcing clinicians to make difficult decisions regarding triage – the fact that some cancers present an immediate threat to survival means that oncology “provides a lens into the major shifts currently underway in clinical care,” Schrag and colleagues write.

They illustrate the point by highlighting systemic chemotherapy, which is provided to a large proportion of patients with advanced cancer. The pandemic has tipped the risk-benefit ratio away from treatments that have a marginal effect on quality or quantity of life, they note. It has forced an “elimination of low-value treatments that were identified by the Choosing Wisely campaign,” the authors write. Up to now, the uptake of recommendations to eliminate these treatments has been slow.

“For example, for most metastatic solid tumors, chemotherapy beyond the third regimen does not improve survival for more than a few weeks; therefore, oncologists are advising supportive care instead. For patients receiving adjuvant therapy for curable cancers, delaying initiation or abbreviating the number of cycles is appropriate. Oncologists are postponing initiation of adjuvant chemotherapy for some estrogen receptor–negative stage II breast cancers by 8 weeks and administering 6 rather than 12 cycles of adjuvant chemotherapy for stage III colorectal cancers,” Schrag and colleagues write.

On the other hand, even in the epicenters of the pandemic, thus far, oncologists are still delivering cancer treatments that have the potential to cure and cannot safely be delayed, they point out. “This includes most patients with new diagnoses of acute leukemia, high-grade lymphoma, and those with chemotherapy-responsive tumors such as testicular, ovarian, and small cell lung cancer. Despite the risks, oncologists are not modifying such treatments because these cancers are likely more lethal than COVID-19.”

It’s the cancer patients who fall in between these two extremes who pose the biggest treatment challenge during this crisis – the patients for whom a delay would have “moderate clinically important adverse influence on quality of life or survival.” In these cases, oncologists are “prescribing marginally less effective regimens that have lower risk of precipitating hospitalization,” the authors note.

These treatments include the use of “white cell growth factor, more stringent neutrophil counts for proceeding with a next cycle of therapy, and omitting use of steroids to manage nausea.” In addition, where possible, oncologists are substituting oral agents for intravenous agents and “myriad other modifications to minimize visits and hospitalizations.”

Most hospitals and outpatient infusion centers now prohibit visitors from accompanying patients, and oncologists are prioritizing conversations with patients about advance directives, healthcare proxies, and end-of-life care preferences. Yet, even here, telehealth offers a new, enhanced layer to those conversations by enabling families to gather with their loved one and the doctor, she said.

This article first appeared on Medscape.com.

Although priority number one lies in controlling the spread of COVID-19, public health researchers are calling attention to the long-term repercussions of the pandemic on children’s health.

School closures could noticeably worsen the epidemic of childhood obesity that already threatens many children in the United States, say Paul Rundle, DrPH, and colleagues from Columbia University Mailman School of Public Health, New York City, in a perspective published online March 30 in Obesity.

“In part, we wrote the perspective to remind people that summer unhealthy weight gain seems to accumulate year to year,” he told Medscape Medical News in an email.

Rundle and colleagues estimate that time spent out of school will double this year because of school closures due to COVID-19. That, along with shelter-in-place orders, will pose challenges both for physical activity and healthy eating among children.

In addition, playgrounds have closed in many areas, and even where parks remain open, social distancing decreases opportunities for exercise. Team sports are on hold, and without physical education taught in schools, many children will not be getting as much active outdoor play as needed.

That’s especially true for children in urban areas, who may find it even more difficult to exercise inside cramped apartments, they add.

As a result, more and more children may turn to sedentary activities, and increased screen time goes hand in hand with childhood overweight and obesity, not just because of the lack of exercise but also because of snacking on unhealthy, empty-calorie foods while glued to the screen.

“We were hoping to get the word out on this issue, do some education or reminding, and at least let people know that this should be something to keep an eye on, among so many other things,” Rundle added.

Excess Eating Because of Stress and Boredom

Jessica Sparks Lilley, MD, director of the Pediatric Diabetes and Lipid Program at the Mississippi Center for Advanced Medicine in Madison, agrees that it is crucial to address these issues.

“Just like adults, children eat in response to emotions, including stress and boredom, and stress levels are high during these uncertain times,” she told Medscape Medical News.

Although both Rundle and Sparks Lilley acknowledged the challenges of finding good solutions at this time, they do offer some tips.

Schools should make physical education and at-home exercise a priority alongside other remote teaching. Physical education teachers could even stream exercise classes to children at home.

Even just walking in the park while maintaining social distancing could be better than nothing, and a brisk walk is probably even better.

Depending on the age of the child, online yoga may also be useful. Even though yoga burns relatively few calories, it incorporates mindfulness training that may be helpful.

“I think focusing on promoting mindful eating as compared to mindless or distracted eating is important. Even in the best of circumstances, it is hard to exercise enough to burn off high energy snacks,” Rundle said.

Additional Stressors From Poverty: Schools Can Help With Meals

Children living in poverty, already the most vulnerable to obesity and related health problems, have additional stressors, add the two experts.

“As more Americans are losing jobs, poverty is a real threat to many of the children I care for. Families living in poverty often rely on processed, high-calorie, low-nutrient foods for survival, because they are inexpensive and shelf-stable,” Sparks Lilley said.

Rundle and colleagues agree: “Our own experiences in supermarkets show...shelves that held...crackers, chips, ramen noodles, soda, sugary cereals, and processed ready-to-eat meals are quite empty. We anticipate that many children will experience higher calorie diets during the pandemic response.”

Similar to how they address food insecurity during summer holidays, school districts have responded by offering grab-and-go meals, Rundle and colleagues note.

To maintain social distancing for people with vulnerable family members, some school districts have also started delivering food using school buses that run along regularly scheduled routes.

Rundle also stresses that farmers’ markets, which often provide foods that appeal to immigrant and ethnic communities, should be considered part of essential food services.

As such, social distancing protocols should be established for them and they should be allowed to stay open, he argues.

“The safety of American children is at stake in many ways. The threat to themselves or their caregivers being infected with COVID-19 is rightly foremost in our concerns,” Sparks Lilley stressed.

“However, there is other fallout to consider. We’ve seen very clearly the need for public health and preventive medicine and can’t let vulnerable children fall through the cracks.”

Rundle agrees. Although it is a “priority” to mitigate the immediate impact of COVID-19, “it is important to consider ways to prevent its long-term effects, including new risks for childhood obesity.”

Rundle and coauthors, as well as Sparks Lilley, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Although priority number one lies in controlling the spread of COVID-19, public health researchers are calling attention to the long-term repercussions of the pandemic on children’s health.

School closures could noticeably worsen the epidemic of childhood obesity that already threatens many children in the United States, say Paul Rundle, DrPH, and colleagues from Columbia University Mailman School of Public Health, New York City, in a perspective published online March 30 in Obesity.

“In part, we wrote the perspective to remind people that summer unhealthy weight gain seems to accumulate year to year,” he told Medscape Medical News in an email.

Rundle and colleagues estimate that time spent out of school will double this year because of school closures due to COVID-19. That, along with shelter-in-place orders, will pose challenges both for physical activity and healthy eating among children.

In addition, playgrounds have closed in many areas, and even where parks remain open, social distancing decreases opportunities for exercise. Team sports are on hold, and without physical education taught in schools, many children will not be getting as much active outdoor play as needed.

That’s especially true for children in urban areas, who may find it even more difficult to exercise inside cramped apartments, they add.

As a result, more and more children may turn to sedentary activities, and increased screen time goes hand in hand with childhood overweight and obesity, not just because of the lack of exercise but also because of snacking on unhealthy, empty-calorie foods while glued to the screen.

“We were hoping to get the word out on this issue, do some education or reminding, and at least let people know that this should be something to keep an eye on, among so many other things,” Rundle added.

Excess Eating Because of Stress and Boredom

Jessica Sparks Lilley, MD, director of the Pediatric Diabetes and Lipid Program at the Mississippi Center for Advanced Medicine in Madison, agrees that it is crucial to address these issues.

“Just like adults, children eat in response to emotions, including stress and boredom, and stress levels are high during these uncertain times,” she told Medscape Medical News.

Although both Rundle and Sparks Lilley acknowledged the challenges of finding good solutions at this time, they do offer some tips.

Schools should make physical education and at-home exercise a priority alongside other remote teaching. Physical education teachers could even stream exercise classes to children at home.

Even just walking in the park while maintaining social distancing could be better than nothing, and a brisk walk is probably even better.

Depending on the age of the child, online yoga may also be useful. Even though yoga burns relatively few calories, it incorporates mindfulness training that may be helpful.

“I think focusing on promoting mindful eating as compared to mindless or distracted eating is important. Even in the best of circumstances, it is hard to exercise enough to burn off high energy snacks,” Rundle said.

Additional Stressors From Poverty: Schools Can Help With Meals

Children living in poverty, already the most vulnerable to obesity and related health problems, have additional stressors, add the two experts.

“As more Americans are losing jobs, poverty is a real threat to many of the children I care for. Families living in poverty often rely on processed, high-calorie, low-nutrient foods for survival, because they are inexpensive and shelf-stable,” Sparks Lilley said.

Rundle and colleagues agree: “Our own experiences in supermarkets show...shelves that held...crackers, chips, ramen noodles, soda, sugary cereals, and processed ready-to-eat meals are quite empty. We anticipate that many children will experience higher calorie diets during the pandemic response.”

Similar to how they address food insecurity during summer holidays, school districts have responded by offering grab-and-go meals, Rundle and colleagues note.

To maintain social distancing for people with vulnerable family members, some school districts have also started delivering food using school buses that run along regularly scheduled routes.

Rundle also stresses that farmers’ markets, which often provide foods that appeal to immigrant and ethnic communities, should be considered part of essential food services.

As such, social distancing protocols should be established for them and they should be allowed to stay open, he argues.

“The safety of American children is at stake in many ways. The threat to themselves or their caregivers being infected with COVID-19 is rightly foremost in our concerns,” Sparks Lilley stressed.

“However, there is other fallout to consider. We’ve seen very clearly the need for public health and preventive medicine and can’t let vulnerable children fall through the cracks.”

Rundle agrees. Although it is a “priority” to mitigate the immediate impact of COVID-19, “it is important to consider ways to prevent its long-term effects, including new risks for childhood obesity.”

Rundle and coauthors, as well as Sparks Lilley, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Although priority number one lies in controlling the spread of COVID-19, public health researchers are calling attention to the long-term repercussions of the pandemic on children’s health.

School closures could noticeably worsen the epidemic of childhood obesity that already threatens many children in the United States, say Paul Rundle, DrPH, and colleagues from Columbia University Mailman School of Public Health, New York City, in a perspective published online March 30 in Obesity.

“In part, we wrote the perspective to remind people that summer unhealthy weight gain seems to accumulate year to year,” he told Medscape Medical News in an email.

Rundle and colleagues estimate that time spent out of school will double this year because of school closures due to COVID-19. That, along with shelter-in-place orders, will pose challenges both for physical activity and healthy eating among children.

In addition, playgrounds have closed in many areas, and even where parks remain open, social distancing decreases opportunities for exercise. Team sports are on hold, and without physical education taught in schools, many children will not be getting as much active outdoor play as needed.

That’s especially true for children in urban areas, who may find it even more difficult to exercise inside cramped apartments, they add.

As a result, more and more children may turn to sedentary activities, and increased screen time goes hand in hand with childhood overweight and obesity, not just because of the lack of exercise but also because of snacking on unhealthy, empty-calorie foods while glued to the screen.

“We were hoping to get the word out on this issue, do some education or reminding, and at least let people know that this should be something to keep an eye on, among so many other things,” Rundle added.

Excess Eating Because of Stress and Boredom

Jessica Sparks Lilley, MD, director of the Pediatric Diabetes and Lipid Program at the Mississippi Center for Advanced Medicine in Madison, agrees that it is crucial to address these issues.

“Just like adults, children eat in response to emotions, including stress and boredom, and stress levels are high during these uncertain times,” she told Medscape Medical News.

Although both Rundle and Sparks Lilley acknowledged the challenges of finding good solutions at this time, they do offer some tips.

Schools should make physical education and at-home exercise a priority alongside other remote teaching. Physical education teachers could even stream exercise classes to children at home.

Even just walking in the park while maintaining social distancing could be better than nothing, and a brisk walk is probably even better.

Depending on the age of the child, online yoga may also be useful. Even though yoga burns relatively few calories, it incorporates mindfulness training that may be helpful.

“I think focusing on promoting mindful eating as compared to mindless or distracted eating is important. Even in the best of circumstances, it is hard to exercise enough to burn off high energy snacks,” Rundle said.

Additional Stressors From Poverty: Schools Can Help With Meals

Children living in poverty, already the most vulnerable to obesity and related health problems, have additional stressors, add the two experts.

“As more Americans are losing jobs, poverty is a real threat to many of the children I care for. Families living in poverty often rely on processed, high-calorie, low-nutrient foods for survival, because they are inexpensive and shelf-stable,” Sparks Lilley said.

Rundle and colleagues agree: “Our own experiences in supermarkets show...shelves that held...crackers, chips, ramen noodles, soda, sugary cereals, and processed ready-to-eat meals are quite empty. We anticipate that many children will experience higher calorie diets during the pandemic response.”

Similar to how they address food insecurity during summer holidays, school districts have responded by offering grab-and-go meals, Rundle and colleagues note.

To maintain social distancing for people with vulnerable family members, some school districts have also started delivering food using school buses that run along regularly scheduled routes.

Rundle also stresses that farmers’ markets, which often provide foods that appeal to immigrant and ethnic communities, should be considered part of essential food services.

As such, social distancing protocols should be established for them and they should be allowed to stay open, he argues.

“The safety of American children is at stake in many ways. The threat to themselves or their caregivers being infected with COVID-19 is rightly foremost in our concerns,” Sparks Lilley stressed.

“However, there is other fallout to consider. We’ve seen very clearly the need for public health and preventive medicine and can’t let vulnerable children fall through the cracks.”

Rundle agrees. Although it is a “priority” to mitigate the immediate impact of COVID-19, “it is important to consider ways to prevent its long-term effects, including new risks for childhood obesity.”

Rundle and coauthors, as well as Sparks Lilley, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A consensus statement on the role of imaging during the acute work-up of COVID-19 patients called for liberal use in patients with moderate to severe clinical features indicative of infection, regardless of their COVID-19 test results, but limited use in patients who present with mild symptoms or are asymptomatic.

The consensus statement on The Role of Imaging in Patient Management during the COVID-19 Pandemic released by the Fleischner Society on April 7 was designed to highlight the “key decision points around imaging” in COVID-19 patients.

“We developed the statement to be applicable across settings” so that each clinic or hospital managing COVID-19 patients could decide the situations where chest radiography (CXR) or CT would work best, said Geoffrey D. Rubin, MD, professor of cardiovascular research, radiology, and bioengineering at Duke University in Durham, N.C., and lead author of the statement.

Written by 15 thoracic radiologists and 10 pulmonologists/intensivists including an anesthesiologist, a pathologist, and additional experts in emergency medicine, infection control, and laboratory medicine, and with members from any of 10 countries on three continents, the panel arrived at agreement by more than 70% for each of the 14 questions.

“I was impressed and a little surprised that consensus was achieved for every question” posed to the panel by the Fleischner Society for Thoracic Imaging and Diagnosis, Dr. Rubin said in an interview. The panel also placed their 14 decisions about imaging within the context of three distinct clinical scenarios chosen to mirror common real-world situations: mild COVID-19 features, moderate to severe features with no critical-resource constraints, and moderate to severe features with constrained resources. The statement also summarized its conclusions as five main recommendations and three additional recommendations.
 

Main recommendations

• Imaging is not routinely indicated for COVID-19 screening in asymptomatic people.
• Imaging is not indicated for patients with mild features of COVID-19 unless they are at risk for disease progression.
• Imaging is indicated for patients with features of moderate to severe COVID-19 regardless of COVID-19 test results.
• Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status.
• When access to CT is limited, chest radiography may be preferred for COVID-19 patients unless features of respiratory worsening warrant using CT.

Additional recommendations

• Daily chest radiographs are not indicated in stable, intubated patients with COVID-19.
• CT is indicated in patients with functional impairment, hypoxemia, or both, after COVID-19 recovery.
• COVID-19 testing is warranted in patients incidentally found to have findings suggestive of COVID-19 on a CT scan.

The statement particularly called out one of its recommendations – that a COVID-19 diagnosis “may be presumed when imaging findings are strongly suggestive of COVID-19 despite negative COVID-19 testing” in a patient who has moderate to severe clinical features of COVID-19 and whose pretest probability is high. The panel voted unanimously in favor of this concept, that imaging is “indicated” in hospitalized patients with moderate to severe symptoms consistent with COVID-19 despite a negative COVID-19 test result. “This guidance represents variance from other published recommendations which advise against the use of imaging for the initial diagnosis of COVID-19,” the statement acknowledged and specifically cited the recommendations issued in March 2020 by the American College of Radiology. Despite that, the ACR and Fleischner recommendations “are not at odds with one another,” maintained Dr. Rubin. The panel based its take on this question on the “direct experience” of its members caring for COVID-19 patients, according to the statement.

“I wholeheartedly agree with the suggested uses of imaging outlined by the panel,” commented Sachin Gupta, MD, FCCP, a pulmonologist and critical care physician in San Francisco. “The consensus statement brings a practical way to consider obtaining imaging. It leaves the door open to local standards and best judgment for using CXR or CT. Many physicians are unclear whether to image low-risk and mildly symptomatic patients. This statement gives support to a watchful waiting approach.” Another recommendation advises against daily CXR in stable, intubated COVID-19 patients. This “now gives backing from an important society and thought leaders while giving an explanation” for why daily imaging is problematic, he noted in an interview. The daily CXR in these patients adds no value, and skipping unneeded imaging minimizes SARS-CoV-2 exposure to radiology personnel, and conserves personal protection equipment, said the statement.

“The Fleischner Society is known worldwide for its recommendations. Having the society lend its weight on triage with imaging for COVID-19 patients is important. I suspect it will help standardize practice.”

Dr. Gupta also highlighted that lung imaging with a portable ultrasound unit has quickly become recognized as a very useful imaging tool with increasing use as the pandemic has unfolded, an option not covered by the Fleischner statement. Study results have “confirmed excellent sensitivity, specificity, and reproducibility” with lung ultrasound, and it’s also “easy to use,” Dr. Gupta said.

Ultrasound chest imaging of COVID-19 patients did not get included in the statement despite the reliance some U.S. sites have already placed on it largely because few on the panel had direct experience using it. “We didn’t feel we could contribute” to a discussion of ultrasound, Dr. Rubin said.

The statement’s recommendations appear to have already begun influencing practice. “The feedback I’ve gotten is that people are relying on them,” said Dr. Rubin, and some programs have sent him screen shots of the recommendations embedded in their local electronic health record.

The Radiological Society of North America is hosting a webinar on the statement on April 17.

mzoler@mdedge.com

A consensus statement on the role of imaging during the acute work-up of COVID-19 patients called for liberal use in patients with moderate to severe clinical features indicative of infection, regardless of their COVID-19 test results, but limited use in patients who present with mild symptoms or are asymptomatic.

The consensus statement on The Role of Imaging in Patient Management during the COVID-19 Pandemic released by the Fleischner Society on April 7 was designed to highlight the “key decision points around imaging” in COVID-19 patients.

“We developed the statement to be applicable across settings” so that each clinic or hospital managing COVID-19 patients could decide the situations where chest radiography (CXR) or CT would work best, said Geoffrey D. Rubin, MD, professor of cardiovascular research, radiology, and bioengineering at Duke University in Durham, N.C., and lead author of the statement.

Written by 15 thoracic radiologists and 10 pulmonologists/intensivists including an anesthesiologist, a pathologist, and additional experts in emergency medicine, infection control, and laboratory medicine, and with members from any of 10 countries on three continents, the panel arrived at agreement by more than 70% for each of the 14 questions.

“I was impressed and a little surprised that consensus was achieved for every question” posed to the panel by the Fleischner Society for Thoracic Imaging and Diagnosis, Dr. Rubin said in an interview. The panel also placed their 14 decisions about imaging within the context of three distinct clinical scenarios chosen to mirror common real-world situations: mild COVID-19 features, moderate to severe features with no critical-resource constraints, and moderate to severe features with constrained resources. The statement also summarized its conclusions as five main recommendations and three additional recommendations.
 

Main recommendations

• Imaging is not routinely indicated for COVID-19 screening in asymptomatic people.
• Imaging is not indicated for patients with mild features of COVID-19 unless they are at risk for disease progression.
• Imaging is indicated for patients with features of moderate to severe COVID-19 regardless of COVID-19 test results.
• Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status.
• When access to CT is limited, chest radiography may be preferred for COVID-19 patients unless features of respiratory worsening warrant using CT.

Additional recommendations

• Daily chest radiographs are not indicated in stable, intubated patients with COVID-19.
• CT is indicated in patients with functional impairment, hypoxemia, or both, after COVID-19 recovery.
• COVID-19 testing is warranted in patients incidentally found to have findings suggestive of COVID-19 on a CT scan.

The statement particularly called out one of its recommendations – that a COVID-19 diagnosis “may be presumed when imaging findings are strongly suggestive of COVID-19 despite negative COVID-19 testing” in a patient who has moderate to severe clinical features of COVID-19 and whose pretest probability is high. The panel voted unanimously in favor of this concept, that imaging is “indicated” in hospitalized patients with moderate to severe symptoms consistent with COVID-19 despite a negative COVID-19 test result. “This guidance represents variance from other published recommendations which advise against the use of imaging for the initial diagnosis of COVID-19,” the statement acknowledged and specifically cited the recommendations issued in March 2020 by the American College of Radiology. Despite that, the ACR and Fleischner recommendations “are not at odds with one another,” maintained Dr. Rubin. The panel based its take on this question on the “direct experience” of its members caring for COVID-19 patients, according to the statement.

“I wholeheartedly agree with the suggested uses of imaging outlined by the panel,” commented Sachin Gupta, MD, FCCP, a pulmonologist and critical care physician in San Francisco. “The consensus statement brings a practical way to consider obtaining imaging. It leaves the door open to local standards and best judgment for using CXR or CT. Many physicians are unclear whether to image low-risk and mildly symptomatic patients. This statement gives support to a watchful waiting approach.” Another recommendation advises against daily CXR in stable, intubated COVID-19 patients. This “now gives backing from an important society and thought leaders while giving an explanation” for why daily imaging is problematic, he noted in an interview. The daily CXR in these patients adds no value, and skipping unneeded imaging minimizes SARS-CoV-2 exposure to radiology personnel, and conserves personal protection equipment, said the statement.

“The Fleischner Society is known worldwide for its recommendations. Having the society lend its weight on triage with imaging for COVID-19 patients is important. I suspect it will help standardize practice.”

Dr. Gupta also highlighted that lung imaging with a portable ultrasound unit has quickly become recognized as a very useful imaging tool with increasing use as the pandemic has unfolded, an option not covered by the Fleischner statement. Study results have “confirmed excellent sensitivity, specificity, and reproducibility” with lung ultrasound, and it’s also “easy to use,” Dr. Gupta said.

Ultrasound chest imaging of COVID-19 patients did not get included in the statement despite the reliance some U.S. sites have already placed on it largely because few on the panel had direct experience using it. “We didn’t feel we could contribute” to a discussion of ultrasound, Dr. Rubin said.

The statement’s recommendations appear to have already begun influencing practice. “The feedback I’ve gotten is that people are relying on them,” said Dr. Rubin, and some programs have sent him screen shots of the recommendations embedded in their local electronic health record.

The Radiological Society of North America is hosting a webinar on the statement on April 17.

mzoler@mdedge.com

A consensus statement on the role of imaging during the acute work-up of COVID-19 patients called for liberal use in patients with moderate to severe clinical features indicative of infection, regardless of their COVID-19 test results, but limited use in patients who present with mild symptoms or are asymptomatic.

The consensus statement on The Role of Imaging in Patient Management during the COVID-19 Pandemic released by the Fleischner Society on April 7 was designed to highlight the “key decision points around imaging” in COVID-19 patients.

“We developed the statement to be applicable across settings” so that each clinic or hospital managing COVID-19 patients could decide the situations where chest radiography (CXR) or CT would work best, said Geoffrey D. Rubin, MD, professor of cardiovascular research, radiology, and bioengineering at Duke University in Durham, N.C., and lead author of the statement.

Written by 15 thoracic radiologists and 10 pulmonologists/intensivists including an anesthesiologist, a pathologist, and additional experts in emergency medicine, infection control, and laboratory medicine, and with members from any of 10 countries on three continents, the panel arrived at agreement by more than 70% for each of the 14 questions.

“I was impressed and a little surprised that consensus was achieved for every question” posed to the panel by the Fleischner Society for Thoracic Imaging and Diagnosis, Dr. Rubin said in an interview. The panel also placed their 14 decisions about imaging within the context of three distinct clinical scenarios chosen to mirror common real-world situations: mild COVID-19 features, moderate to severe features with no critical-resource constraints, and moderate to severe features with constrained resources. The statement also summarized its conclusions as five main recommendations and three additional recommendations.
 

Main recommendations

• Imaging is not routinely indicated for COVID-19 screening in asymptomatic people.
• Imaging is not indicated for patients with mild features of COVID-19 unless they are at risk for disease progression.
• Imaging is indicated for patients with features of moderate to severe COVID-19 regardless of COVID-19 test results.
• Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status.
• When access to CT is limited, chest radiography may be preferred for COVID-19 patients unless features of respiratory worsening warrant using CT.

Additional recommendations

• Daily chest radiographs are not indicated in stable, intubated patients with COVID-19.
• CT is indicated in patients with functional impairment, hypoxemia, or both, after COVID-19 recovery.
• COVID-19 testing is warranted in patients incidentally found to have findings suggestive of COVID-19 on a CT scan.

The statement particularly called out one of its recommendations – that a COVID-19 diagnosis “may be presumed when imaging findings are strongly suggestive of COVID-19 despite negative COVID-19 testing” in a patient who has moderate to severe clinical features of COVID-19 and whose pretest probability is high. The panel voted unanimously in favor of this concept, that imaging is “indicated” in hospitalized patients with moderate to severe symptoms consistent with COVID-19 despite a negative COVID-19 test result. “This guidance represents variance from other published recommendations which advise against the use of imaging for the initial diagnosis of COVID-19,” the statement acknowledged and specifically cited the recommendations issued in March 2020 by the American College of Radiology. Despite that, the ACR and Fleischner recommendations “are not at odds with one another,” maintained Dr. Rubin. The panel based its take on this question on the “direct experience” of its members caring for COVID-19 patients, according to the statement.

“I wholeheartedly agree with the suggested uses of imaging outlined by the panel,” commented Sachin Gupta, MD, FCCP, a pulmonologist and critical care physician in San Francisco. “The consensus statement brings a practical way to consider obtaining imaging. It leaves the door open to local standards and best judgment for using CXR or CT. Many physicians are unclear whether to image low-risk and mildly symptomatic patients. This statement gives support to a watchful waiting approach.” Another recommendation advises against daily CXR in stable, intubated COVID-19 patients. This “now gives backing from an important society and thought leaders while giving an explanation” for why daily imaging is problematic, he noted in an interview. The daily CXR in these patients adds no value, and skipping unneeded imaging minimizes SARS-CoV-2 exposure to radiology personnel, and conserves personal protection equipment, said the statement.

“The Fleischner Society is known worldwide for its recommendations. Having the society lend its weight on triage with imaging for COVID-19 patients is important. I suspect it will help standardize practice.”

Dr. Gupta also highlighted that lung imaging with a portable ultrasound unit has quickly become recognized as a very useful imaging tool with increasing use as the pandemic has unfolded, an option not covered by the Fleischner statement. Study results have “confirmed excellent sensitivity, specificity, and reproducibility” with lung ultrasound, and it’s also “easy to use,” Dr. Gupta said.

Ultrasound chest imaging of COVID-19 patients did not get included in the statement despite the reliance some U.S. sites have already placed on it largely because few on the panel had direct experience using it. “We didn’t feel we could contribute” to a discussion of ultrasound, Dr. Rubin said.

The statement’s recommendations appear to have already begun influencing practice. “The feedback I’ve gotten is that people are relying on them,” said Dr. Rubin, and some programs have sent him screen shots of the recommendations embedded in their local electronic health record.

The Radiological Society of North America is hosting a webinar on the statement on April 17.

mzoler@mdedge.com

Patients infected by the COVID-19 virus may benefit from treatments that dampen the renin-angiotensin system, according to a review of several animal studies. These preclinical findings generally support the positions taken in recent week by several cardiology societies that recommended patients taking drugs that moderate the renin-angiotensin system stay on these treatments.

“In patients with cardiovascular disease and SARS-CoV2, the use of ACE inhibitors, ARBs [angiotensin receptor blockers], or MRAs [mineralocorticoid-receptor antagonists] may be favorable as a method to endogenously upregulate ACE2 as a compensatory mechanism that provides anti-inflammatory, antifibrotic, and antithrombotic support as well as reduction in progression of vascular/cardiac remodeling and heart failure,” wrote Jeffrey Bander, MD, and his associates in a report published online (J Am Coll Cardiol. 2020 Apr 15. doi: 10.1016/j.jacc.2020.04.028).

“Based on our review, we hypothesize cardiovascular patients with COVID-19 should remain on RAS [renin-angiotensin system] inhibitors given the protective effects of the ACE2 pathway until RAS blockade is proven to increase the risk to COVID-19,” said the researchers, who are affiliated with the Icahn School of Medicine at Mount Sinai in New York.

The ACE2 protein, found both in human blood as well as in cell membranes, especially cells of the lungs, heart, kidneys, and gastrointestinal tissues, functions as both a key enzyme in RAS regulation as well as the primary cell receptor for entry of SARS-CoV2.

Their conclusion jibed with both a joint statement in March from the American College of Cardiology, American Heart Association, and the Heart Failure Society of America; and with the conclusions of a review organized by the European Society of Hypertension’s COVID-19 Task Force (Cardiovasc Res. 2020 Apr 15. doi: 10.1093/cvr/cvaa097).

In their review, the Mount Sinai authors described results from several animal studies suggesting that ACE2 and its associated signaling proteins could potentially be a “valuable therapeutic target.” They also highlighted several clinical intervention studies recently launched to target ACE2, related proteins, and regulation of this arm of the RAS.

Currently, “no data support any conclusive effects of the use of RAS inhibitors in patients with COVID-19,” they concluded. They acknowledged that “the question remains whether the use of ACE inhibitors, ARBs, and MRAs should be avoided in the setting of SARS-CoV infection,” but emphasized that “adequate data on the effects of RAS inhibition in COVID-19 patients is not available,” with more data becoming available soon from ongoing clinical studies.

None of the authors had any disclosures.

mzoler@mdedge.com

Patients infected by the COVID-19 virus may benefit from treatments that dampen the renin-angiotensin system, according to a review of several animal studies. These preclinical findings generally support the positions taken in recent week by several cardiology societies that recommended patients taking drugs that moderate the renin-angiotensin system stay on these treatments.

“In patients with cardiovascular disease and SARS-CoV2, the use of ACE inhibitors, ARBs [angiotensin receptor blockers], or MRAs [mineralocorticoid-receptor antagonists] may be favorable as a method to endogenously upregulate ACE2 as a compensatory mechanism that provides anti-inflammatory, antifibrotic, and antithrombotic support as well as reduction in progression of vascular/cardiac remodeling and heart failure,” wrote Jeffrey Bander, MD, and his associates in a report published online (J Am Coll Cardiol. 2020 Apr 15. doi: 10.1016/j.jacc.2020.04.028).

“Based on our review, we hypothesize cardiovascular patients with COVID-19 should remain on RAS [renin-angiotensin system] inhibitors given the protective effects of the ACE2 pathway until RAS blockade is proven to increase the risk to COVID-19,” said the researchers, who are affiliated with the Icahn School of Medicine at Mount Sinai in New York.

The ACE2 protein, found both in human blood as well as in cell membranes, especially cells of the lungs, heart, kidneys, and gastrointestinal tissues, functions as both a key enzyme in RAS regulation as well as the primary cell receptor for entry of SARS-CoV2.

Their conclusion jibed with both a joint statement in March from the American College of Cardiology, American Heart Association, and the Heart Failure Society of America; and with the conclusions of a review organized by the European Society of Hypertension’s COVID-19 Task Force (Cardiovasc Res. 2020 Apr 15. doi: 10.1093/cvr/cvaa097).

In their review, the Mount Sinai authors described results from several animal studies suggesting that ACE2 and its associated signaling proteins could potentially be a “valuable therapeutic target.” They also highlighted several clinical intervention studies recently launched to target ACE2, related proteins, and regulation of this arm of the RAS.

Currently, “no data support any conclusive effects of the use of RAS inhibitors in patients with COVID-19,” they concluded. They acknowledged that “the question remains whether the use of ACE inhibitors, ARBs, and MRAs should be avoided in the setting of SARS-CoV infection,” but emphasized that “adequate data on the effects of RAS inhibition in COVID-19 patients is not available,” with more data becoming available soon from ongoing clinical studies.

None of the authors had any disclosures.

mzoler@mdedge.com

Patients infected by the COVID-19 virus may benefit from treatments that dampen the renin-angiotensin system, according to a review of several animal studies. These preclinical findings generally support the positions taken in recent week by several cardiology societies that recommended patients taking drugs that moderate the renin-angiotensin system stay on these treatments.

“In patients with cardiovascular disease and SARS-CoV2, the use of ACE inhibitors, ARBs [angiotensin receptor blockers], or MRAs [mineralocorticoid-receptor antagonists] may be favorable as a method to endogenously upregulate ACE2 as a compensatory mechanism that provides anti-inflammatory, antifibrotic, and antithrombotic support as well as reduction in progression of vascular/cardiac remodeling and heart failure,” wrote Jeffrey Bander, MD, and his associates in a report published online (J Am Coll Cardiol. 2020 Apr 15. doi: 10.1016/j.jacc.2020.04.028).

“Based on our review, we hypothesize cardiovascular patients with COVID-19 should remain on RAS [renin-angiotensin system] inhibitors given the protective effects of the ACE2 pathway until RAS blockade is proven to increase the risk to COVID-19,” said the researchers, who are affiliated with the Icahn School of Medicine at Mount Sinai in New York.

The ACE2 protein, found both in human blood as well as in cell membranes, especially cells of the lungs, heart, kidneys, and gastrointestinal tissues, functions as both a key enzyme in RAS regulation as well as the primary cell receptor for entry of SARS-CoV2.

Their conclusion jibed with both a joint statement in March from the American College of Cardiology, American Heart Association, and the Heart Failure Society of America; and with the conclusions of a review organized by the European Society of Hypertension’s COVID-19 Task Force (Cardiovasc Res. 2020 Apr 15. doi: 10.1093/cvr/cvaa097).

In their review, the Mount Sinai authors described results from several animal studies suggesting that ACE2 and its associated signaling proteins could potentially be a “valuable therapeutic target.” They also highlighted several clinical intervention studies recently launched to target ACE2, related proteins, and regulation of this arm of the RAS.

Currently, “no data support any conclusive effects of the use of RAS inhibitors in patients with COVID-19,” they concluded. They acknowledged that “the question remains whether the use of ACE inhibitors, ARBs, and MRAs should be avoided in the setting of SARS-CoV infection,” but emphasized that “adequate data on the effects of RAS inhibition in COVID-19 patients is not available,” with more data becoming available soon from ongoing clinical studies.

None of the authors had any disclosures.

mzoler@mdedge.com

Mass social distancing and social isolation to prevent the spread of a deadly disease, along with technological tools that allow social communication and continued work and school, is an unprecedented situation.

Stockbyte/Thinkstock.com

The current reality of most people’s lives during the COVID-19 pandemic has the potential to induce or exacerbate sleep problems, though it may also present some with an opportunity to improve sleep, wrote Ellemarije Altena, PhD, of the University of Bordeaux (France), and her colleagues in a recent research review in the Journal of Sleep Research.

The review was conducted by a task force of the European Academy for Cognitive Behavioural Therapy for Insomnia. The European CBT-I Academy is an initiative of the European Insomnia Network to promote implementation and dissemination of treatment.

After discussing the known effects of stress, confinement, and altered schedules on sleep, the authors present recommendations on ways to manage sleep problems such as insomnia in the general public and potentially encourage people to take advantage of the opportunity to align their schedules with their natural circadian rhythms. Physicians may find the recommendations helpful in advising patients with sleep problems related to the COVID-19 emergency.

“Being forced to stay at home, work from home, do homeschooling with children, drastically minimize outings, reduce social interaction or work many more hours under stressful circumstances, and in parallel manage the attendant health risks, can have a major impact on daily functioning and nighttime sleep,” Dr. Altena and colleagues wrote.

There may also be a lag time in physicians hearing about changes in sleep or sleeping problems from patients, said Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah in Salt Lake City. “There may actually be some improvement in sleep durations given that most folks are working from home with more time with family and less work-related stress,” he said in an interview. “In terms of sleep or other effects on worsening of psychiatric problems, it is still not clear what the overall effects are going to be.”

Although daylight has the biggest impact on regulating circadian rhythms, artificial light, meal times, diet, and amount of physical activity can also have an influence. Negative effects on sleep can result from both excessively high activity levels, such as stress and work overload, or excessively low levels, such as from depression or confinement, the authors note.

The current situation also opens the door to interactions between stress, sleep, anxiety, and risk of PTSD. “Those sensitive to stress-related sleep disruption are more likely to develop chronic insomnia,” which, in combination with a major stressor, is a risk factor for PTSD, the authors write. They note that 7% of Wuhan residents, the city in China where the virus appears to have originated, particularly women, reported PTSD symptoms after the COVID-19 outbreak, and anxiety was highest in those under age 35 years and those who followed news about the disease for more than 3 hours a day.

Better sleep quality and fewer early morning awakenings, however, appeared to be protective against PTSD symptoms. The authors note the value of physical exercise, cognitive interventions, and relaxation techniques, including meditation, for reducing stress and milder symptoms of PTSD.

“Some patients are sleeping a bit better because of the pace of things has slowed down a bit,” said Anne C. Trainor, a nurse practitioner and instructor in the neurology department’s sleep disorders program at Oregon Health & Science University in Portland, who was not involved in the study. “Keeping a regular schedule for sleeping and eating, getting exercise daily – preferably in sunlight and not just before bedtime – and using relaxation or mindfulness practice and cognitive interventions to help manage anxiety” were the key takeaways from this review, Ms. Trainor said in an interview.


 

Home confinement, stressors and sleep

A wide range of stressors could affect sleep during COVID-19 social distancing interventions, including “major changes in routines, living with uncertainty,” and anxiety about health, the economic situation, and how long this situation will last, the authors write.

Parents must juggle work, homeschooling, and ordinary household errands and management. Meanwhile, entrepreneurs, small business owners ,and workers in entertainment, hospitality and food service must contend with anxiety about job uncertainty and financial security. For anyone working from home, disruptions to work and home routines can make it difficult to associate being home with relaxation – and sleep.

“The more regular our sleep schedule is the better quality our sleep tends to be, but it is a struggle when we don’t have separate spaces to work and parent in,” Ms. Trainor said.

At the same time, “confinement-related stress may be caused by an inability to engage in rewarding activities, such as visiting friends and family, shopping, attending cultural and sports events, and visiting bars or restaurants,” the authors write. “Spending more time with family in a limited space can also induce stress, particularly in situations where there are preexisting family difficulties.”

Being stuck at home may lead to less daylight exposure than usual, reduced physical activity, and increased eating, which can contribute to weight gain and other health risks. However, “the effect of stress from confinement, loss of work, and health concerns needs to be individualized and may be difficult to generalize,” Dr. Sundar said.

The authors of the review note the established associations between too little social interaction, increased stress, and poor sleep quality, though loneliness mediates this relationship. Loneliness is also a risk during this time, with or without online social interaction.

Children and teens may also have difficulty sleeping, which can affect their behavioral and emotional regulation, and primary caregivers experience more stress while juggling childcare, household duties, and work.

“While many parents share childcare and household responsibilities, in most families these tasks are still predominantly managed by mothers,” the authors added.

“Sharing responsibilities between parents and not overworking just one parent is key,” said Brandon M. Seay MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. He also recommended trying to incorporate work into the day while kids are doing online learning.

Ms. Trainor agreed that trading off responsibilities between parents is ideal, though the challenge is greater for single parents. It may be possible for some to take family leave, but not all families have that option, she said.

The study authors also point out a Catch-22 for many people: The blurred boundary between home life and work life can undermine work productivity and efficiency, thereby increasing stress. “Healthy sleep may be a key protective factor to cope positively with these challenges, although adequate opportunity to sleep may be affected by increased time pressure of work, childcare, and household requirements.”

Dr. Seay advises adults to try to get at least 6-8 hours of sleep each night, even taking advantage of a later waking time – if the kids also sleep in – to help. “If anything, the ability to sleep later and wake up later is of benefit for a lot of my teenage patients,” he said in an interview.

In fact, the study authors also address possible positive effects on sleep for some people during the current situation. Since social support can improve sleep quality, social media interaction might provide some social support, though it’s not the same as meeting people in person and “screen exposure may hamper sleep quality when used close to bedtime.”

Some people may actually have an opportunity to get more daylight exposure or exercise, which can improve sleep, and some, especially night owls and teenagers, may be able to align their daily schedules more closely to their natural circadian rhythms.

“Given that we are not bound by usual work or social schedules, there may be a tendency to drift to our sleep chronotypes,” especially for teenagers, Dr. Sundar said.

For some, this may be their first opportunity to learn what their chronotype is, Dr. Seay said.

“It is always advantageous to ‘obey’ your natural sleep timing, [although] it simply isn’t always the most efficient outside of our current situation,” he said. “Use this as a time to figure out your natural sleep timing if you constantly have issues being able to wake up in the morning. Now that you don’t have to be up for work or school, you can figure out what time works for you.”

At the same time, if you have an extreme circadian rhythm disorder, especially an irregular one, it may still be best to try to keep a regular sleep schedule to avoid feeling isolated if others are socializing while you’re asleep, Ms. Trainor said.

The authors similarly note the limits of potential benefits during this time, noting that they “may not be enough to counteract the negative effects of the increased work and family requirements, as well as the overwhelming levels of stress and anxiety about the well-being of oneself and others, and the negative effects of confinement for family social reactions.”
 

Treating stress, anxiety, and insomnia

The first-line treatment for chronic insomnia is cognitive-behavioral therapy for insomnia, but “recent evidence shows that cognitive-behavioral therapy can also serve to treat sudden-onset (acute) insomnia due to rapid stress-causing situation changes,” the authors noted. They also reviewed the key elements of CBT-I: stimulus control, sleep hygiene, relaxation interventions, cognitive reappraisal, paradoxical intention, and sleep restriction.

CBT-I lends very naturally to telemedicine, Dr. Seay, Dr. Sundar, and Ms. Trainor all agreed.

“I actually see this current situation as an opportunity for health care practices and providers to expand the reach of telemedicine – due to necessity – which will hopefully continue after confinement has been lifted worldwide,” Dr. Seay said.  

Dr. Sundar pointed to research supporting CBT-I online and several apps that can be used for it, such as SHUTi and Sleepio. Ms. Trainor noted that the Cleveland Clinic offers a basic CBT-I online class for $40.

The authors note that prescribing medication is generally discouraged because it lacks evidence for long-term effectiveness of chronic insomnia, but it might be worth considering as a second-line therapy for acute insomnia from outside stressors, such as home confinement, if CBT-I doesn’t work or isn’t possible. Pharmacologic treatment can include benzodiazepines, hypnotic benzodiazepine receptor agonists, or sedating antidepressants, particularly if used for a comorbid mood disorder.

The authors then offer general recommendations for improving sleep that doctors can pass on to their patients:

• Get up and go to bed at approximately the same times daily.
• Schedule 15-minute breaks during the day to manage stress and reflect on worries and the situation.
• Reserve the bed for sleep and sex only; not for working, watching TV, using the computer, or doing other activities.
• Try to follow your natural sleep rhythm as much as possible.
• Use social media as stress relief, an opportunity to communicate with friends and family, and distraction, especially with uplifting stories or humor.
• Leave devices out of the bedroom.
• Limit your exposure to news about the COVID-19 pandemic.
• Exercise regularly, ideally in daylight.
• Look for ways to stay busy and distracted, including making your home or bedroom more comfortable if possible.
• Get as much daylight during the day as possible, and keep lights dim or dark at night.
• Engage in familiar, comfortable, relaxing activities before bedtime.
• If your daily activity level is lower, eat less as well, ideally at least 2 hours before going to bed.

The authors also offered recommendations specifically for families:

• Divide child care, home maintenance, and chores between adults, being sure not to let the lion’s share fall on women.
• Maintain regular sleep times for children and spend the 30 minutes before their bedtime doing a calming, familiar activity that both the children and parents enjoy.
• “While using computer, smartphones, and watching TV more than usual may be inevitable in confinement, avoid technological devices after dinner or too close to bedtime.”
• Ensure your child has daily physical activity, keep a relatively consistent schedule or routine, expose them to as much daylight or bright light as possible during the day, and try to limit their bed use only to sleeping if possible. “Parents need to be involved in setting schedules for sleep and meal times so that kids do not get into sleep patterns that are difficult to change when school starts back,” Dr. Sundar said. “Limiting screen time is also important especially during nighttime.”
• Reassure children if they wake up anxious at night.

SOURCE: Altena E et al. J Sleep Res. 2020 Apr 4. doi: 10.1111/jsr.13052.

Mass social distancing and social isolation to prevent the spread of a deadly disease, along with technological tools that allow social communication and continued work and school, is an unprecedented situation.

Stockbyte/Thinkstock.com

The current reality of most people’s lives during the COVID-19 pandemic has the potential to induce or exacerbate sleep problems, though it may also present some with an opportunity to improve sleep, wrote Ellemarije Altena, PhD, of the University of Bordeaux (France), and her colleagues in a recent research review in the Journal of Sleep Research.

The review was conducted by a task force of the European Academy for Cognitive Behavioural Therapy for Insomnia. The European CBT-I Academy is an initiative of the European Insomnia Network to promote implementation and dissemination of treatment.

After discussing the known effects of stress, confinement, and altered schedules on sleep, the authors present recommendations on ways to manage sleep problems such as insomnia in the general public and potentially encourage people to take advantage of the opportunity to align their schedules with their natural circadian rhythms. Physicians may find the recommendations helpful in advising patients with sleep problems related to the COVID-19 emergency.

“Being forced to stay at home, work from home, do homeschooling with children, drastically minimize outings, reduce social interaction or work many more hours under stressful circumstances, and in parallel manage the attendant health risks, can have a major impact on daily functioning and nighttime sleep,” Dr. Altena and colleagues wrote.

There may also be a lag time in physicians hearing about changes in sleep or sleeping problems from patients, said Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah in Salt Lake City. “There may actually be some improvement in sleep durations given that most folks are working from home with more time with family and less work-related stress,” he said in an interview. “In terms of sleep or other effects on worsening of psychiatric problems, it is still not clear what the overall effects are going to be.”

Although daylight has the biggest impact on regulating circadian rhythms, artificial light, meal times, diet, and amount of physical activity can also have an influence. Negative effects on sleep can result from both excessively high activity levels, such as stress and work overload, or excessively low levels, such as from depression or confinement, the authors note.

The current situation also opens the door to interactions between stress, sleep, anxiety, and risk of PTSD. “Those sensitive to stress-related sleep disruption are more likely to develop chronic insomnia,” which, in combination with a major stressor, is a risk factor for PTSD, the authors write. They note that 7% of Wuhan residents, the city in China where the virus appears to have originated, particularly women, reported PTSD symptoms after the COVID-19 outbreak, and anxiety was highest in those under age 35 years and those who followed news about the disease for more than 3 hours a day.

Better sleep quality and fewer early morning awakenings, however, appeared to be protective against PTSD symptoms. The authors note the value of physical exercise, cognitive interventions, and relaxation techniques, including meditation, for reducing stress and milder symptoms of PTSD.

“Some patients are sleeping a bit better because of the pace of things has slowed down a bit,” said Anne C. Trainor, a nurse practitioner and instructor in the neurology department’s sleep disorders program at Oregon Health & Science University in Portland, who was not involved in the study. “Keeping a regular schedule for sleeping and eating, getting exercise daily – preferably in sunlight and not just before bedtime – and using relaxation or mindfulness practice and cognitive interventions to help manage anxiety” were the key takeaways from this review, Ms. Trainor said in an interview.


 

Home confinement, stressors and sleep

A wide range of stressors could affect sleep during COVID-19 social distancing interventions, including “major changes in routines, living with uncertainty,” and anxiety about health, the economic situation, and how long this situation will last, the authors write.

Parents must juggle work, homeschooling, and ordinary household errands and management. Meanwhile, entrepreneurs, small business owners ,and workers in entertainment, hospitality and food service must contend with anxiety about job uncertainty and financial security. For anyone working from home, disruptions to work and home routines can make it difficult to associate being home with relaxation – and sleep.

“The more regular our sleep schedule is the better quality our sleep tends to be, but it is a struggle when we don’t have separate spaces to work and parent in,” Ms. Trainor said.

At the same time, “confinement-related stress may be caused by an inability to engage in rewarding activities, such as visiting friends and family, shopping, attending cultural and sports events, and visiting bars or restaurants,” the authors write. “Spending more time with family in a limited space can also induce stress, particularly in situations where there are preexisting family difficulties.”

Being stuck at home may lead to less daylight exposure than usual, reduced physical activity, and increased eating, which can contribute to weight gain and other health risks. However, “the effect of stress from confinement, loss of work, and health concerns needs to be individualized and may be difficult to generalize,” Dr. Sundar said.

The authors of the review note the established associations between too little social interaction, increased stress, and poor sleep quality, though loneliness mediates this relationship. Loneliness is also a risk during this time, with or without online social interaction.

Children and teens may also have difficulty sleeping, which can affect their behavioral and emotional regulation, and primary caregivers experience more stress while juggling childcare, household duties, and work.

“While many parents share childcare and household responsibilities, in most families these tasks are still predominantly managed by mothers,” the authors added.

“Sharing responsibilities between parents and not overworking just one parent is key,” said Brandon M. Seay MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. He also recommended trying to incorporate work into the day while kids are doing online learning.

Ms. Trainor agreed that trading off responsibilities between parents is ideal, though the challenge is greater for single parents. It may be possible for some to take family leave, but not all families have that option, she said.

The study authors also point out a Catch-22 for many people: The blurred boundary between home life and work life can undermine work productivity and efficiency, thereby increasing stress. “Healthy sleep may be a key protective factor to cope positively with these challenges, although adequate opportunity to sleep may be affected by increased time pressure of work, childcare, and household requirements.”

Dr. Seay advises adults to try to get at least 6-8 hours of sleep each night, even taking advantage of a later waking time – if the kids also sleep in – to help. “If anything, the ability to sleep later and wake up later is of benefit for a lot of my teenage patients,” he said in an interview.

In fact, the study authors also address possible positive effects on sleep for some people during the current situation. Since social support can improve sleep quality, social media interaction might provide some social support, though it’s not the same as meeting people in person and “screen exposure may hamper sleep quality when used close to bedtime.”

Some people may actually have an opportunity to get more daylight exposure or exercise, which can improve sleep, and some, especially night owls and teenagers, may be able to align their daily schedules more closely to their natural circadian rhythms.

“Given that we are not bound by usual work or social schedules, there may be a tendency to drift to our sleep chronotypes,” especially for teenagers, Dr. Sundar said.

For some, this may be their first opportunity to learn what their chronotype is, Dr. Seay said.

“It is always advantageous to ‘obey’ your natural sleep timing, [although] it simply isn’t always the most efficient outside of our current situation,” he said. “Use this as a time to figure out your natural sleep timing if you constantly have issues being able to wake up in the morning. Now that you don’t have to be up for work or school, you can figure out what time works for you.”

At the same time, if you have an extreme circadian rhythm disorder, especially an irregular one, it may still be best to try to keep a regular sleep schedule to avoid feeling isolated if others are socializing while you’re asleep, Ms. Trainor said.

The authors similarly note the limits of potential benefits during this time, noting that they “may not be enough to counteract the negative effects of the increased work and family requirements, as well as the overwhelming levels of stress and anxiety about the well-being of oneself and others, and the negative effects of confinement for family social reactions.”
 

Treating stress, anxiety, and insomnia

The first-line treatment for chronic insomnia is cognitive-behavioral therapy for insomnia, but “recent evidence shows that cognitive-behavioral therapy can also serve to treat sudden-onset (acute) insomnia due to rapid stress-causing situation changes,” the authors noted. They also reviewed the key elements of CBT-I: stimulus control, sleep hygiene, relaxation interventions, cognitive reappraisal, paradoxical intention, and sleep restriction.

CBT-I lends very naturally to telemedicine, Dr. Seay, Dr. Sundar, and Ms. Trainor all agreed.

“I actually see this current situation as an opportunity for health care practices and providers to expand the reach of telemedicine – due to necessity – which will hopefully continue after confinement has been lifted worldwide,” Dr. Seay said.  

Dr. Sundar pointed to research supporting CBT-I online and several apps that can be used for it, such as SHUTi and Sleepio. Ms. Trainor noted that the Cleveland Clinic offers a basic CBT-I online class for $40.

The authors note that prescribing medication is generally discouraged because it lacks evidence for long-term effectiveness of chronic insomnia, but it might be worth considering as a second-line therapy for acute insomnia from outside stressors, such as home confinement, if CBT-I doesn’t work or isn’t possible. Pharmacologic treatment can include benzodiazepines, hypnotic benzodiazepine receptor agonists, or sedating antidepressants, particularly if used for a comorbid mood disorder.

The authors then offer general recommendations for improving sleep that doctors can pass on to their patients:

• Get up and go to bed at approximately the same times daily.
• Schedule 15-minute breaks during the day to manage stress and reflect on worries and the situation.
• Reserve the bed for sleep and sex only; not for working, watching TV, using the computer, or doing other activities.
• Try to follow your natural sleep rhythm as much as possible.
• Use social media as stress relief, an opportunity to communicate with friends and family, and distraction, especially with uplifting stories or humor.
• Leave devices out of the bedroom.
• Limit your exposure to news about the COVID-19 pandemic.
• Exercise regularly, ideally in daylight.
• Look for ways to stay busy and distracted, including making your home or bedroom more comfortable if possible.
• Get as much daylight during the day as possible, and keep lights dim or dark at night.
• Engage in familiar, comfortable, relaxing activities before bedtime.
• If your daily activity level is lower, eat less as well, ideally at least 2 hours before going to bed.

The authors also offered recommendations specifically for families:

• Divide child care, home maintenance, and chores between adults, being sure not to let the lion’s share fall on women.
• Maintain regular sleep times for children and spend the 30 minutes before their bedtime doing a calming, familiar activity that both the children and parents enjoy.
• “While using computer, smartphones, and watching TV more than usual may be inevitable in confinement, avoid technological devices after dinner or too close to bedtime.”
• Ensure your child has daily physical activity, keep a relatively consistent schedule or routine, expose them to as much daylight or bright light as possible during the day, and try to limit their bed use only to sleeping if possible. “Parents need to be involved in setting schedules for sleep and meal times so that kids do not get into sleep patterns that are difficult to change when school starts back,” Dr. Sundar said. “Limiting screen time is also important especially during nighttime.”
• Reassure children if they wake up anxious at night.

SOURCE: Altena E et al. J Sleep Res. 2020 Apr 4. doi: 10.1111/jsr.13052.

Mass social distancing and social isolation to prevent the spread of a deadly disease, along with technological tools that allow social communication and continued work and school, is an unprecedented situation.

Stockbyte/Thinkstock.com

The current reality of most people’s lives during the COVID-19 pandemic has the potential to induce or exacerbate sleep problems, though it may also present some with an opportunity to improve sleep, wrote Ellemarije Altena, PhD, of the University of Bordeaux (France), and her colleagues in a recent research review in the Journal of Sleep Research.

The review was conducted by a task force of the European Academy for Cognitive Behavioural Therapy for Insomnia. The European CBT-I Academy is an initiative of the European Insomnia Network to promote implementation and dissemination of treatment.

After discussing the known effects of stress, confinement, and altered schedules on sleep, the authors present recommendations on ways to manage sleep problems such as insomnia in the general public and potentially encourage people to take advantage of the opportunity to align their schedules with their natural circadian rhythms. Physicians may find the recommendations helpful in advising patients with sleep problems related to the COVID-19 emergency.

“Being forced to stay at home, work from home, do homeschooling with children, drastically minimize outings, reduce social interaction or work many more hours under stressful circumstances, and in parallel manage the attendant health risks, can have a major impact on daily functioning and nighttime sleep,” Dr. Altena and colleagues wrote.

There may also be a lag time in physicians hearing about changes in sleep or sleeping problems from patients, said Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah in Salt Lake City. “There may actually be some improvement in sleep durations given that most folks are working from home with more time with family and less work-related stress,” he said in an interview. “In terms of sleep or other effects on worsening of psychiatric problems, it is still not clear what the overall effects are going to be.”

Although daylight has the biggest impact on regulating circadian rhythms, artificial light, meal times, diet, and amount of physical activity can also have an influence. Negative effects on sleep can result from both excessively high activity levels, such as stress and work overload, or excessively low levels, such as from depression or confinement, the authors note.

The current situation also opens the door to interactions between stress, sleep, anxiety, and risk of PTSD. “Those sensitive to stress-related sleep disruption are more likely to develop chronic insomnia,” which, in combination with a major stressor, is a risk factor for PTSD, the authors write. They note that 7% of Wuhan residents, the city in China where the virus appears to have originated, particularly women, reported PTSD symptoms after the COVID-19 outbreak, and anxiety was highest in those under age 35 years and those who followed news about the disease for more than 3 hours a day.

Better sleep quality and fewer early morning awakenings, however, appeared to be protective against PTSD symptoms. The authors note the value of physical exercise, cognitive interventions, and relaxation techniques, including meditation, for reducing stress and milder symptoms of PTSD.

“Some patients are sleeping a bit better because of the pace of things has slowed down a bit,” said Anne C. Trainor, a nurse practitioner and instructor in the neurology department’s sleep disorders program at Oregon Health & Science University in Portland, who was not involved in the study. “Keeping a regular schedule for sleeping and eating, getting exercise daily – preferably in sunlight and not just before bedtime – and using relaxation or mindfulness practice and cognitive interventions to help manage anxiety” were the key takeaways from this review, Ms. Trainor said in an interview.


 

Home confinement, stressors and sleep

A wide range of stressors could affect sleep during COVID-19 social distancing interventions, including “major changes in routines, living with uncertainty,” and anxiety about health, the economic situation, and how long this situation will last, the authors write.

Parents must juggle work, homeschooling, and ordinary household errands and management. Meanwhile, entrepreneurs, small business owners ,and workers in entertainment, hospitality and food service must contend with anxiety about job uncertainty and financial security. For anyone working from home, disruptions to work and home routines can make it difficult to associate being home with relaxation – and sleep.

“The more regular our sleep schedule is the better quality our sleep tends to be, but it is a struggle when we don’t have separate spaces to work and parent in,” Ms. Trainor said.

At the same time, “confinement-related stress may be caused by an inability to engage in rewarding activities, such as visiting friends and family, shopping, attending cultural and sports events, and visiting bars or restaurants,” the authors write. “Spending more time with family in a limited space can also induce stress, particularly in situations where there are preexisting family difficulties.”

Being stuck at home may lead to less daylight exposure than usual, reduced physical activity, and increased eating, which can contribute to weight gain and other health risks. However, “the effect of stress from confinement, loss of work, and health concerns needs to be individualized and may be difficult to generalize,” Dr. Sundar said.

The authors of the review note the established associations between too little social interaction, increased stress, and poor sleep quality, though loneliness mediates this relationship. Loneliness is also a risk during this time, with or without online social interaction.

Children and teens may also have difficulty sleeping, which can affect their behavioral and emotional regulation, and primary caregivers experience more stress while juggling childcare, household duties, and work.

“While many parents share childcare and household responsibilities, in most families these tasks are still predominantly managed by mothers,” the authors added.

“Sharing responsibilities between parents and not overworking just one parent is key,” said Brandon M. Seay MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. He also recommended trying to incorporate work into the day while kids are doing online learning.

Ms. Trainor agreed that trading off responsibilities between parents is ideal, though the challenge is greater for single parents. It may be possible for some to take family leave, but not all families have that option, she said.

The study authors also point out a Catch-22 for many people: The blurred boundary between home life and work life can undermine work productivity and efficiency, thereby increasing stress. “Healthy sleep may be a key protective factor to cope positively with these challenges, although adequate opportunity to sleep may be affected by increased time pressure of work, childcare, and household requirements.”

Dr. Seay advises adults to try to get at least 6-8 hours of sleep each night, even taking advantage of a later waking time – if the kids also sleep in – to help. “If anything, the ability to sleep later and wake up later is of benefit for a lot of my teenage patients,” he said in an interview.

In fact, the study authors also address possible positive effects on sleep for some people during the current situation. Since social support can improve sleep quality, social media interaction might provide some social support, though it’s not the same as meeting people in person and “screen exposure may hamper sleep quality when used close to bedtime.”

Some people may actually have an opportunity to get more daylight exposure or exercise, which can improve sleep, and some, especially night owls and teenagers, may be able to align their daily schedules more closely to their natural circadian rhythms.

“Given that we are not bound by usual work or social schedules, there may be a tendency to drift to our sleep chronotypes,” especially for teenagers, Dr. Sundar said.

For some, this may be their first opportunity to learn what their chronotype is, Dr. Seay said.

“It is always advantageous to ‘obey’ your natural sleep timing, [although] it simply isn’t always the most efficient outside of our current situation,” he said. “Use this as a time to figure out your natural sleep timing if you constantly have issues being able to wake up in the morning. Now that you don’t have to be up for work or school, you can figure out what time works for you.”

At the same time, if you have an extreme circadian rhythm disorder, especially an irregular one, it may still be best to try to keep a regular sleep schedule to avoid feeling isolated if others are socializing while you’re asleep, Ms. Trainor said.

The authors similarly note the limits of potential benefits during this time, noting that they “may not be enough to counteract the negative effects of the increased work and family requirements, as well as the overwhelming levels of stress and anxiety about the well-being of oneself and others, and the negative effects of confinement for family social reactions.”
 

Treating stress, anxiety, and insomnia

The first-line treatment for chronic insomnia is cognitive-behavioral therapy for insomnia, but “recent evidence shows that cognitive-behavioral therapy can also serve to treat sudden-onset (acute) insomnia due to rapid stress-causing situation changes,” the authors noted. They also reviewed the key elements of CBT-I: stimulus control, sleep hygiene, relaxation interventions, cognitive reappraisal, paradoxical intention, and sleep restriction.

CBT-I lends very naturally to telemedicine, Dr. Seay, Dr. Sundar, and Ms. Trainor all agreed.

“I actually see this current situation as an opportunity for health care practices and providers to expand the reach of telemedicine – due to necessity – which will hopefully continue after confinement has been lifted worldwide,” Dr. Seay said.  

Dr. Sundar pointed to research supporting CBT-I online and several apps that can be used for it, such as SHUTi and Sleepio. Ms. Trainor noted that the Cleveland Clinic offers a basic CBT-I online class for $40.

The authors note that prescribing medication is generally discouraged because it lacks evidence for long-term effectiveness of chronic insomnia, but it might be worth considering as a second-line therapy for acute insomnia from outside stressors, such as home confinement, if CBT-I doesn’t work or isn’t possible. Pharmacologic treatment can include benzodiazepines, hypnotic benzodiazepine receptor agonists, or sedating antidepressants, particularly if used for a comorbid mood disorder.

The authors then offer general recommendations for improving sleep that doctors can pass on to their patients:

• Get up and go to bed at approximately the same times daily.
• Schedule 15-minute breaks during the day to manage stress and reflect on worries and the situation.
• Reserve the bed for sleep and sex only; not for working, watching TV, using the computer, or doing other activities.
• Try to follow your natural sleep rhythm as much as possible.
• Use social media as stress relief, an opportunity to communicate with friends and family, and distraction, especially with uplifting stories or humor.
• Leave devices out of the bedroom.
• Limit your exposure to news about the COVID-19 pandemic.
• Exercise regularly, ideally in daylight.
• Look for ways to stay busy and distracted, including making your home or bedroom more comfortable if possible.
• Get as much daylight during the day as possible, and keep lights dim or dark at night.
• Engage in familiar, comfortable, relaxing activities before bedtime.
• If your daily activity level is lower, eat less as well, ideally at least 2 hours before going to bed.

The authors also offered recommendations specifically for families:

• Divide child care, home maintenance, and chores between adults, being sure not to let the lion’s share fall on women.
• Maintain regular sleep times for children and spend the 30 minutes before their bedtime doing a calming, familiar activity that both the children and parents enjoy.
• “While using computer, smartphones, and watching TV more than usual may be inevitable in confinement, avoid technological devices after dinner or too close to bedtime.”
• Ensure your child has daily physical activity, keep a relatively consistent schedule or routine, expose them to as much daylight or bright light as possible during the day, and try to limit their bed use only to sleeping if possible. “Parents need to be involved in setting schedules for sleep and meal times so that kids do not get into sleep patterns that are difficult to change when school starts back,” Dr. Sundar said. “Limiting screen time is also important especially during nighttime.”
• Reassure children if they wake up anxious at night.

SOURCE: Altena E et al. J Sleep Res. 2020 Apr 4. doi: 10.1111/jsr.13052.