Rheumatology News

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

[email protected]

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

[email protected]

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

[email protected]

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

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

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

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

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

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

Lessons from the past

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

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

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

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

These include:

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

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

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

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

Concerning spike in gun sales

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lessons from the past

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

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

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

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

These include:

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

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

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

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

Concerning spike in gun sales

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lessons from the past

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

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

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

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

These include:

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

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

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

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

Concerning spike in gun sales

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

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

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

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

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

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

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

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

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

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

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

Presentation and cardiac risks from COVID-19

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

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

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

Acute cardiac injuries in COVID-19

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

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

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

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

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

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

Management of acute cardiac issues in COVID-19

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

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

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

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

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

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

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

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

Case examples

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

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

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

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

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

Controversy on ACEI/ARB

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

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

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

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

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

Cardiac concern about hydroxychloroquine and chloroquine

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

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

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

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

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

Key points

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Presentation and cardiac risks from COVID-19

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

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

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

Acute cardiac injuries in COVID-19

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

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

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

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

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

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

Management of acute cardiac issues in COVID-19

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

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

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

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

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

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

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

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

Case examples

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

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

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

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

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

Controversy on ACEI/ARB

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

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

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

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

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

Cardiac concern about hydroxychloroquine and chloroquine

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

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

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

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

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

Key points

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Presentation and cardiac risks from COVID-19

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

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

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

Acute cardiac injuries in COVID-19

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

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

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

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

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

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

Management of acute cardiac issues in COVID-19

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

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

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

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

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

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

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

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

Case examples

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

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

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

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

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

Controversy on ACEI/ARB

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

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

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

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

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

Cardiac concern about hydroxychloroquine and chloroquine

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

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

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

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

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

Key points

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tomacco/iStock/Getty Images

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

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

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

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

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

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

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

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

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

Tomacco/iStock/Getty Images

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

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

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

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

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

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

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

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

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

Tomacco/iStock/Getty Images

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

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

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

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

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

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

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

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

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

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

The data were published online April 23 in JAMA Cardiology.

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

Additional studies

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

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

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

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

New Wuhan study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

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

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

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

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

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

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

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

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

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

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

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

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

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

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