User login
Treatments for COVID-19: Update for hospitalists
Most patients with COVID-19 will have a mild presentation and not require hospitalization or any treatment. Inpatient management revolves around the supportive management of the most common complications of severe COVID-19, which includes pneumonia, hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), and septic shock.
Currently, there is no clinically proven specific antiviral treatment for COVID-19. A few antivirals and treatment modalities have been studied and used, with the hope of decreasing mortality and improving recovery time for those with moderate to severe cases of COVID-19.
Remdesivir
The antiviral remdesivir was the second drug to receive emergency use authorization by the Food and Drug Administration for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. Severe disease is defined as patients with an oxygen saturation less than 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO).
Remdesivir is a nucleotide analogue that has shown in vitro antiviral activity against a range of RNA viruses. It acts by causing premature termination of viral RNA transcription. Remdesivir is administered intravenously and the recommended dose is 200 mg on day 1, followed by 100 mg daily for various time courses.
A few clinical studies have reported benefits of remdesivir rather than no remdesivir for treatment of severe COVID-19 in hospitalized patients. The Infectious Diseases Society of America (IDSA) recommends 5 days of remdesivir in patients with severe COVID-19 on noninvasive supplemental oxygen and 10 days treatment for those on mechanical ventilation and ECMO. In a randomized, uncontrolled, phase 3 trial, investigators compared 5-day (n = 200) versus 10-day (n = 197) courses of remdesivir in patients with severe COVID-19. Clinical data revealed no differences in outcomes in the two groups.
Common reported adverse effects of the drug include elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and gastrointestinal symptoms including nausea, vomiting, and hematochezia. There is insufficient data on using remdesivir in patients requiring dialysis.
Corticosteroids
Is dexamethasone effective for treating COVID-19? In the early days of the COVID-19 pandemic, corticosteroids were not recommended with the fear that, if started too soon, you could blunt the body’s natural defense system and that could allow the virus to thrive. Recent clinical data has shown clinical benefits and decreased mortality with the use of dexamethasone in patients with severe COVID-19 infection because glucocorticoids may modulate inflammation-mediated lung injury and reduce progression to respiratory failure and death.
The Recovery Trial was an open label study which used 6-mg once-daily doses of dexamethasone for up to 10 days or until hospital discharge if sooner. The study concluded that the use of dexamethasone for up to 10 days in hospitalized patients with severe COVID-19 resulted in lower 28-day mortality than usual care.
Dexamethasone is recommended in COVID-19 patients who require supplemental oxygen. If dexamethasone is not available, alternative forms of steroids – prednisone, methylprednisolone, or hydrocortisone – can be used. However, there is no clear evidence that the use of other steroids provides the same benefit as dexamethasone.
Both the IDSA and National Institutes of Health guidelines have recommended the use of steroids. However, clinicians should closely monitor the adverse effects like hyperglycemia, secondary infections, psychiatric effects, and avascular necrosis.
Convalescent plasma
Convalescent plasma is a blood product believed to provide passive antibody therapy through the transmission of neutralizing viral antibodies. Convalescent plasma has been used for decades for different viral infections including the treatment of H1N1 influenza virus, polio, chicken pox, measles, SARS-CoV-1, and MERS-CoV.
On Aug. 23, 2020, the FDA issued an emergency use authorization for investigational convalescent plasma for the treatment of COVID-19 in hospitalized patients. The FDA recommends neutralizing antibodies of at least 1:160. However, such assays have not been widely available and titers in plasma have often not been assessed prior to infusion.
There is no current standard recommended dosing. Most study protocols infuse 1-2 units of convalescent plasma for persons with COVID-19.
There is insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19. Existing data suggest that, if a benefit exists, convalescent plasma is most useful when given early and with a high titer of neutralizing antibodies.
The adverse effects of convalescent plasma is very similar to the receipt of other blood products, including allergic reactions to the plasma, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and acquisition of infections, though the latter is rare because of the rigorous screening process.
Tocilizumab
Tocilizumab is a recombinant humanized monoclonal antibody that binds to interleukin (IL)-6 receptors. Tocilizumab is currently FDA approved for the treatment of severe or life-threatening cytokine release syndrome that is associated with chimeric antigen–receptor (CAR) T-cell therapy and for the treatment of rheumatologic disorders.
The interest in using tocilizumab to treat persons with COVID-19 is based on the observations that a subset of patients with COVID-19 develop a severe inflammatory response that can result in cytokine storm resulting in ARDS, multiorgan failure, and potentially death. Very high levels of IL-6 have been observed in these individuals, thereby suggesting IL-6 may play a central role in the acute clinical decompensation seen with severe COVID-19.
The optimal dosing of tocilizumab in patients with COVID-19 is not known. The FDA recommends dosing of tocilizumab for cytokine release syndrome should not exceed 800 mg. There is limited data about the potential benefit of tocilizumab in patients with COVID-19. The COVACTA trial showed no difference between tocilizumab and placebo in regard to mortality. The time to hospital discharge was shorter in patients treated with tocilizumab; however, the difference was not statistically significant.
Reported adverse effects of tocilizumab include increase in ALT and AST, increased risk of serious infections (especially tuberculosis and invasive fungal infections), reactivation of hepatitis B virus, and rare reports of gastrointestinal perforation.
Hydroxychloroquine
Hydroxycholoroquine (HCQ) and its sister drug chloroquine, have been used for many decades as treatment for malaria and autoimmune diseases. HCQ gained widespread popularity in the early days of the COVID-19 pandemic when clinical studies showed that it had significant in vitro activity against SARS-CoV-2, which provided the rationale for its use in the treatment and prevention of COVID-19 infection.
It was the first drug that was authorized for emergency use by the FDA during the COVID-19 pandemic. However, On June 15, 2020, because of accumulating harmful data, the FDA revoked the emergency authorization use of HCQ as a COVID-19 treatment.
Randomized controlled trials showed that patients treated with HCQ experienced a longer hospital stay with increase in mortality rates and increased likelihood of being placed on mechanical ventilation. In addition, studies revealed an increase in QT prolongation in patients treated with HCQ, especially when coadministered with azithromycin, which can lead to torsades de pointes, ventricular tachycardia, and sudden cardiac death.
The IDSA and National Institutes of Health, both recommend against the use of hydroxychloroquine with or without azithromycin to treat COVID-19 because the harms outweigh the benefits, even if high quality RCTs were to become available in the future.
Other drugs
There have been experimental studies on other medications for the treatment of COVID-19, including losartan, amlodipine, ivermectin, famotidine, Anakinra, Bruton’s tyrosine kinase inhibitors such as ibrutinib, and Janus kinase inhibitors, such as tofacitinib. Additionally, a few supplements such as vitamin C, vitamin D, and zinc have been used in both inpatient and outpatient settings for COVID-19 treatment. Polyclonal antibodies are being investigated in phase 3 trials. However, the data is insufficient, and the effectiveness of these drugs is unknown. The COVID-19 treatment guidelines panel recommends against the use of these treatment modalities.
Dr Tiyouh is an infectious diseases physician at Keystone Health in Chambersburg, Pa. Dr. Tenneti completed medical school at Vydehi Institute of Medical Sciences and Research Centre in Karnataka, India, and is interested in pursuing internal medicine residency. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg Hospital and Waynesboro (Pa.) Hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson, and a member of the editorial advisory board for The Hospitalist.
Sources
Goldman JD et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 May 27. doi: 10.1056/NEJMoa2015301.
Beigel JH et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764
Wang Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-78.
National Institutes of Health. COVID-19 Treatment Guidelines.
Infectious Diseases Society of America. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19.
Joyner et al. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest. 2020;130(9):4791-7.
Luo P et al. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-8.
Centers for Disease Control and Prevention. Healthcare Workers: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19).
University of Washington. COVID-19 Treatments: Prescribing Information, Clinical Studies, and Slide Decks.
Most patients with COVID-19 will have a mild presentation and not require hospitalization or any treatment. Inpatient management revolves around the supportive management of the most common complications of severe COVID-19, which includes pneumonia, hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), and septic shock.
Currently, there is no clinically proven specific antiviral treatment for COVID-19. A few antivirals and treatment modalities have been studied and used, with the hope of decreasing mortality and improving recovery time for those with moderate to severe cases of COVID-19.
Remdesivir
The antiviral remdesivir was the second drug to receive emergency use authorization by the Food and Drug Administration for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. Severe disease is defined as patients with an oxygen saturation less than 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO).
Remdesivir is a nucleotide analogue that has shown in vitro antiviral activity against a range of RNA viruses. It acts by causing premature termination of viral RNA transcription. Remdesivir is administered intravenously and the recommended dose is 200 mg on day 1, followed by 100 mg daily for various time courses.
A few clinical studies have reported benefits of remdesivir rather than no remdesivir for treatment of severe COVID-19 in hospitalized patients. The Infectious Diseases Society of America (IDSA) recommends 5 days of remdesivir in patients with severe COVID-19 on noninvasive supplemental oxygen and 10 days treatment for those on mechanical ventilation and ECMO. In a randomized, uncontrolled, phase 3 trial, investigators compared 5-day (n = 200) versus 10-day (n = 197) courses of remdesivir in patients with severe COVID-19. Clinical data revealed no differences in outcomes in the two groups.
Common reported adverse effects of the drug include elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and gastrointestinal symptoms including nausea, vomiting, and hematochezia. There is insufficient data on using remdesivir in patients requiring dialysis.
Corticosteroids
Is dexamethasone effective for treating COVID-19? In the early days of the COVID-19 pandemic, corticosteroids were not recommended with the fear that, if started too soon, you could blunt the body’s natural defense system and that could allow the virus to thrive. Recent clinical data has shown clinical benefits and decreased mortality with the use of dexamethasone in patients with severe COVID-19 infection because glucocorticoids may modulate inflammation-mediated lung injury and reduce progression to respiratory failure and death.
The Recovery Trial was an open label study which used 6-mg once-daily doses of dexamethasone for up to 10 days or until hospital discharge if sooner. The study concluded that the use of dexamethasone for up to 10 days in hospitalized patients with severe COVID-19 resulted in lower 28-day mortality than usual care.
Dexamethasone is recommended in COVID-19 patients who require supplemental oxygen. If dexamethasone is not available, alternative forms of steroids – prednisone, methylprednisolone, or hydrocortisone – can be used. However, there is no clear evidence that the use of other steroids provides the same benefit as dexamethasone.
Both the IDSA and National Institutes of Health guidelines have recommended the use of steroids. However, clinicians should closely monitor the adverse effects like hyperglycemia, secondary infections, psychiatric effects, and avascular necrosis.
Convalescent plasma
Convalescent plasma is a blood product believed to provide passive antibody therapy through the transmission of neutralizing viral antibodies. Convalescent plasma has been used for decades for different viral infections including the treatment of H1N1 influenza virus, polio, chicken pox, measles, SARS-CoV-1, and MERS-CoV.
On Aug. 23, 2020, the FDA issued an emergency use authorization for investigational convalescent plasma for the treatment of COVID-19 in hospitalized patients. The FDA recommends neutralizing antibodies of at least 1:160. However, such assays have not been widely available and titers in plasma have often not been assessed prior to infusion.
There is no current standard recommended dosing. Most study protocols infuse 1-2 units of convalescent plasma for persons with COVID-19.
There is insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19. Existing data suggest that, if a benefit exists, convalescent plasma is most useful when given early and with a high titer of neutralizing antibodies.
The adverse effects of convalescent plasma is very similar to the receipt of other blood products, including allergic reactions to the plasma, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and acquisition of infections, though the latter is rare because of the rigorous screening process.
Tocilizumab
Tocilizumab is a recombinant humanized monoclonal antibody that binds to interleukin (IL)-6 receptors. Tocilizumab is currently FDA approved for the treatment of severe or life-threatening cytokine release syndrome that is associated with chimeric antigen–receptor (CAR) T-cell therapy and for the treatment of rheumatologic disorders.
The interest in using tocilizumab to treat persons with COVID-19 is based on the observations that a subset of patients with COVID-19 develop a severe inflammatory response that can result in cytokine storm resulting in ARDS, multiorgan failure, and potentially death. Very high levels of IL-6 have been observed in these individuals, thereby suggesting IL-6 may play a central role in the acute clinical decompensation seen with severe COVID-19.
The optimal dosing of tocilizumab in patients with COVID-19 is not known. The FDA recommends dosing of tocilizumab for cytokine release syndrome should not exceed 800 mg. There is limited data about the potential benefit of tocilizumab in patients with COVID-19. The COVACTA trial showed no difference between tocilizumab and placebo in regard to mortality. The time to hospital discharge was shorter in patients treated with tocilizumab; however, the difference was not statistically significant.
Reported adverse effects of tocilizumab include increase in ALT and AST, increased risk of serious infections (especially tuberculosis and invasive fungal infections), reactivation of hepatitis B virus, and rare reports of gastrointestinal perforation.
Hydroxychloroquine
Hydroxycholoroquine (HCQ) and its sister drug chloroquine, have been used for many decades as treatment for malaria and autoimmune diseases. HCQ gained widespread popularity in the early days of the COVID-19 pandemic when clinical studies showed that it had significant in vitro activity against SARS-CoV-2, which provided the rationale for its use in the treatment and prevention of COVID-19 infection.
It was the first drug that was authorized for emergency use by the FDA during the COVID-19 pandemic. However, On June 15, 2020, because of accumulating harmful data, the FDA revoked the emergency authorization use of HCQ as a COVID-19 treatment.
Randomized controlled trials showed that patients treated with HCQ experienced a longer hospital stay with increase in mortality rates and increased likelihood of being placed on mechanical ventilation. In addition, studies revealed an increase in QT prolongation in patients treated with HCQ, especially when coadministered with azithromycin, which can lead to torsades de pointes, ventricular tachycardia, and sudden cardiac death.
The IDSA and National Institutes of Health, both recommend against the use of hydroxychloroquine with or without azithromycin to treat COVID-19 because the harms outweigh the benefits, even if high quality RCTs were to become available in the future.
Other drugs
There have been experimental studies on other medications for the treatment of COVID-19, including losartan, amlodipine, ivermectin, famotidine, Anakinra, Bruton’s tyrosine kinase inhibitors such as ibrutinib, and Janus kinase inhibitors, such as tofacitinib. Additionally, a few supplements such as vitamin C, vitamin D, and zinc have been used in both inpatient and outpatient settings for COVID-19 treatment. Polyclonal antibodies are being investigated in phase 3 trials. However, the data is insufficient, and the effectiveness of these drugs is unknown. The COVID-19 treatment guidelines panel recommends against the use of these treatment modalities.
Dr Tiyouh is an infectious diseases physician at Keystone Health in Chambersburg, Pa. Dr. Tenneti completed medical school at Vydehi Institute of Medical Sciences and Research Centre in Karnataka, India, and is interested in pursuing internal medicine residency. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg Hospital and Waynesboro (Pa.) Hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson, and a member of the editorial advisory board for The Hospitalist.
Sources
Goldman JD et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 May 27. doi: 10.1056/NEJMoa2015301.
Beigel JH et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764
Wang Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-78.
National Institutes of Health. COVID-19 Treatment Guidelines.
Infectious Diseases Society of America. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19.
Joyner et al. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest. 2020;130(9):4791-7.
Luo P et al. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-8.
Centers for Disease Control and Prevention. Healthcare Workers: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19).
University of Washington. COVID-19 Treatments: Prescribing Information, Clinical Studies, and Slide Decks.
Most patients with COVID-19 will have a mild presentation and not require hospitalization or any treatment. Inpatient management revolves around the supportive management of the most common complications of severe COVID-19, which includes pneumonia, hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), and septic shock.
Currently, there is no clinically proven specific antiviral treatment for COVID-19. A few antivirals and treatment modalities have been studied and used, with the hope of decreasing mortality and improving recovery time for those with moderate to severe cases of COVID-19.
Remdesivir
The antiviral remdesivir was the second drug to receive emergency use authorization by the Food and Drug Administration for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. Severe disease is defined as patients with an oxygen saturation less than 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO).
Remdesivir is a nucleotide analogue that has shown in vitro antiviral activity against a range of RNA viruses. It acts by causing premature termination of viral RNA transcription. Remdesivir is administered intravenously and the recommended dose is 200 mg on day 1, followed by 100 mg daily for various time courses.
A few clinical studies have reported benefits of remdesivir rather than no remdesivir for treatment of severe COVID-19 in hospitalized patients. The Infectious Diseases Society of America (IDSA) recommends 5 days of remdesivir in patients with severe COVID-19 on noninvasive supplemental oxygen and 10 days treatment for those on mechanical ventilation and ECMO. In a randomized, uncontrolled, phase 3 trial, investigators compared 5-day (n = 200) versus 10-day (n = 197) courses of remdesivir in patients with severe COVID-19. Clinical data revealed no differences in outcomes in the two groups.
Common reported adverse effects of the drug include elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and gastrointestinal symptoms including nausea, vomiting, and hematochezia. There is insufficient data on using remdesivir in patients requiring dialysis.
Corticosteroids
Is dexamethasone effective for treating COVID-19? In the early days of the COVID-19 pandemic, corticosteroids were not recommended with the fear that, if started too soon, you could blunt the body’s natural defense system and that could allow the virus to thrive. Recent clinical data has shown clinical benefits and decreased mortality with the use of dexamethasone in patients with severe COVID-19 infection because glucocorticoids may modulate inflammation-mediated lung injury and reduce progression to respiratory failure and death.
The Recovery Trial was an open label study which used 6-mg once-daily doses of dexamethasone for up to 10 days or until hospital discharge if sooner. The study concluded that the use of dexamethasone for up to 10 days in hospitalized patients with severe COVID-19 resulted in lower 28-day mortality than usual care.
Dexamethasone is recommended in COVID-19 patients who require supplemental oxygen. If dexamethasone is not available, alternative forms of steroids – prednisone, methylprednisolone, or hydrocortisone – can be used. However, there is no clear evidence that the use of other steroids provides the same benefit as dexamethasone.
Both the IDSA and National Institutes of Health guidelines have recommended the use of steroids. However, clinicians should closely monitor the adverse effects like hyperglycemia, secondary infections, psychiatric effects, and avascular necrosis.
Convalescent plasma
Convalescent plasma is a blood product believed to provide passive antibody therapy through the transmission of neutralizing viral antibodies. Convalescent plasma has been used for decades for different viral infections including the treatment of H1N1 influenza virus, polio, chicken pox, measles, SARS-CoV-1, and MERS-CoV.
On Aug. 23, 2020, the FDA issued an emergency use authorization for investigational convalescent plasma for the treatment of COVID-19 in hospitalized patients. The FDA recommends neutralizing antibodies of at least 1:160. However, such assays have not been widely available and titers in plasma have often not been assessed prior to infusion.
There is no current standard recommended dosing. Most study protocols infuse 1-2 units of convalescent plasma for persons with COVID-19.
There is insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19. Existing data suggest that, if a benefit exists, convalescent plasma is most useful when given early and with a high titer of neutralizing antibodies.
The adverse effects of convalescent plasma is very similar to the receipt of other blood products, including allergic reactions to the plasma, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and acquisition of infections, though the latter is rare because of the rigorous screening process.
Tocilizumab
Tocilizumab is a recombinant humanized monoclonal antibody that binds to interleukin (IL)-6 receptors. Tocilizumab is currently FDA approved for the treatment of severe or life-threatening cytokine release syndrome that is associated with chimeric antigen–receptor (CAR) T-cell therapy and for the treatment of rheumatologic disorders.
The interest in using tocilizumab to treat persons with COVID-19 is based on the observations that a subset of patients with COVID-19 develop a severe inflammatory response that can result in cytokine storm resulting in ARDS, multiorgan failure, and potentially death. Very high levels of IL-6 have been observed in these individuals, thereby suggesting IL-6 may play a central role in the acute clinical decompensation seen with severe COVID-19.
The optimal dosing of tocilizumab in patients with COVID-19 is not known. The FDA recommends dosing of tocilizumab for cytokine release syndrome should not exceed 800 mg. There is limited data about the potential benefit of tocilizumab in patients with COVID-19. The COVACTA trial showed no difference between tocilizumab and placebo in regard to mortality. The time to hospital discharge was shorter in patients treated with tocilizumab; however, the difference was not statistically significant.
Reported adverse effects of tocilizumab include increase in ALT and AST, increased risk of serious infections (especially tuberculosis and invasive fungal infections), reactivation of hepatitis B virus, and rare reports of gastrointestinal perforation.
Hydroxychloroquine
Hydroxycholoroquine (HCQ) and its sister drug chloroquine, have been used for many decades as treatment for malaria and autoimmune diseases. HCQ gained widespread popularity in the early days of the COVID-19 pandemic when clinical studies showed that it had significant in vitro activity against SARS-CoV-2, which provided the rationale for its use in the treatment and prevention of COVID-19 infection.
It was the first drug that was authorized for emergency use by the FDA during the COVID-19 pandemic. However, On June 15, 2020, because of accumulating harmful data, the FDA revoked the emergency authorization use of HCQ as a COVID-19 treatment.
Randomized controlled trials showed that patients treated with HCQ experienced a longer hospital stay with increase in mortality rates and increased likelihood of being placed on mechanical ventilation. In addition, studies revealed an increase in QT prolongation in patients treated with HCQ, especially when coadministered with azithromycin, which can lead to torsades de pointes, ventricular tachycardia, and sudden cardiac death.
The IDSA and National Institutes of Health, both recommend against the use of hydroxychloroquine with or without azithromycin to treat COVID-19 because the harms outweigh the benefits, even if high quality RCTs were to become available in the future.
Other drugs
There have been experimental studies on other medications for the treatment of COVID-19, including losartan, amlodipine, ivermectin, famotidine, Anakinra, Bruton’s tyrosine kinase inhibitors such as ibrutinib, and Janus kinase inhibitors, such as tofacitinib. Additionally, a few supplements such as vitamin C, vitamin D, and zinc have been used in both inpatient and outpatient settings for COVID-19 treatment. Polyclonal antibodies are being investigated in phase 3 trials. However, the data is insufficient, and the effectiveness of these drugs is unknown. The COVID-19 treatment guidelines panel recommends against the use of these treatment modalities.
Dr Tiyouh is an infectious diseases physician at Keystone Health in Chambersburg, Pa. Dr. Tenneti completed medical school at Vydehi Institute of Medical Sciences and Research Centre in Karnataka, India, and is interested in pursuing internal medicine residency. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg Hospital and Waynesboro (Pa.) Hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson, and a member of the editorial advisory board for The Hospitalist.
Sources
Goldman JD et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 May 27. doi: 10.1056/NEJMoa2015301.
Beigel JH et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764
Wang Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-78.
National Institutes of Health. COVID-19 Treatment Guidelines.
Infectious Diseases Society of America. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19.
Joyner et al. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest. 2020;130(9):4791-7.
Luo P et al. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-8.
Centers for Disease Control and Prevention. Healthcare Workers: Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19).
University of Washington. COVID-19 Treatments: Prescribing Information, Clinical Studies, and Slide Decks.
COVID-19 in pediatric patients: What the hospitalist needs to know
Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.
The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.
SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.
COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
The pediatric population: Disease patterns and transmission
The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.1
Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.2 These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.
Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.3 The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.
Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.4 This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.
The youngest patient to be diagnosed with COVID-19 was a newborn of less than 24 hours old from England, whose mother also tested positive for SARS-CoV-2. However, Chen et al. found no evidence of vertical transmission of the virus from infected pregnant women to their newborns.5
Although the risk of infection in children has been reported to be low, the infection has been shown to be particularly severe in adults with compromised immune systems and chronic health conditions. Thus immunocompromised children and those with chronic health conditions are thought to be at a higher risk for contracting the infection, with the probability for increased morbidity and mortality. Some of these risk groups include premature infants, young infants, immunocompromised children, and children with chronic health conditions like asthma, diabetes, and others. It is essential that caregivers, healthy siblings, and other family members are protected from contracting the infection in order to protect these vulnerable children. Given the high infectivity of SARS-CoV-2, the implications of infected children attending schools and daycares may be far reaching if there is delayed identification of the infection. For these reasons, it is important to closely monitor and promptly test children living with infected adults to prevent the spread. It may become necessary to close schools to mitigate transmission.
Schools and daycares should work with their local health departments and physicians in case of infected individuals in their community. In China, authorities closed schools and allowed students to receive virtual education from home, which may be a reasonable choice depending on resources.
Current challenges
Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.
Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
Conclusion
Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.
Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.6 Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
References
1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.
2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.
4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.
5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.
6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.
Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.
The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.
SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.
COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
The pediatric population: Disease patterns and transmission
The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.1
Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.2 These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.
Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.3 The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.
Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.4 This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.
The youngest patient to be diagnosed with COVID-19 was a newborn of less than 24 hours old from England, whose mother also tested positive for SARS-CoV-2. However, Chen et al. found no evidence of vertical transmission of the virus from infected pregnant women to their newborns.5
Although the risk of infection in children has been reported to be low, the infection has been shown to be particularly severe in adults with compromised immune systems and chronic health conditions. Thus immunocompromised children and those with chronic health conditions are thought to be at a higher risk for contracting the infection, with the probability for increased morbidity and mortality. Some of these risk groups include premature infants, young infants, immunocompromised children, and children with chronic health conditions like asthma, diabetes, and others. It is essential that caregivers, healthy siblings, and other family members are protected from contracting the infection in order to protect these vulnerable children. Given the high infectivity of SARS-CoV-2, the implications of infected children attending schools and daycares may be far reaching if there is delayed identification of the infection. For these reasons, it is important to closely monitor and promptly test children living with infected adults to prevent the spread. It may become necessary to close schools to mitigate transmission.
Schools and daycares should work with their local health departments and physicians in case of infected individuals in their community. In China, authorities closed schools and allowed students to receive virtual education from home, which may be a reasonable choice depending on resources.
Current challenges
Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.
Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
Conclusion
Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.
Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.6 Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
References
1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.
2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.
4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.
5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.
6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.
Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.
The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.
SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.
COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
The pediatric population: Disease patterns and transmission
The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.1
Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.2 These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.
Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.3 The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.
Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.4 This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.
The youngest patient to be diagnosed with COVID-19 was a newborn of less than 24 hours old from England, whose mother also tested positive for SARS-CoV-2. However, Chen et al. found no evidence of vertical transmission of the virus from infected pregnant women to their newborns.5
Although the risk of infection in children has been reported to be low, the infection has been shown to be particularly severe in adults with compromised immune systems and chronic health conditions. Thus immunocompromised children and those with chronic health conditions are thought to be at a higher risk for contracting the infection, with the probability for increased morbidity and mortality. Some of these risk groups include premature infants, young infants, immunocompromised children, and children with chronic health conditions like asthma, diabetes, and others. It is essential that caregivers, healthy siblings, and other family members are protected from contracting the infection in order to protect these vulnerable children. Given the high infectivity of SARS-CoV-2, the implications of infected children attending schools and daycares may be far reaching if there is delayed identification of the infection. For these reasons, it is important to closely monitor and promptly test children living with infected adults to prevent the spread. It may become necessary to close schools to mitigate transmission.
Schools and daycares should work with their local health departments and physicians in case of infected individuals in their community. In China, authorities closed schools and allowed students to receive virtual education from home, which may be a reasonable choice depending on resources.
Current challenges
Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.
Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
Conclusion
Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.
Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.6 Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
References
1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.
2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.
4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.
5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.
6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.