COVID-19 Updates

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at pdnews@mdedge.com.

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at pdnews@mdedge.com.

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at pdnews@mdedge.com.

In addition to affecting our personal lives, coronavirus disease 2019 (COVID-19) has altered the way we practice psychiatry. Telepsychiatry—the delivery of mental health services via remote communication—is being used to replace face-to-face outpatient encounters. Several rules and regulations governing the provision of care and prescribing have been temporarily modified or suspended to allow clinicians to more easily use telepsychiatry to care for their patients. Although these requirements are continually changing, here I review some of the telepsychiatry rules and regulations clinicians need to understand to minimize their risk for liability.

Changes in light of COVID-19

In March 2020, the Centers for Medicare & Medicaid Services (CMS) released guidance that allows Medicare beneficiaries to receive various services at home through telehealth without having to travel to a doctor’s office or hospital.¹ Many commercial insurers also are allowing patients to receive telehealth services in their home. The US Department of Health & Human Services Office for Civil Rights, which enforces the Health Insurance Portability and Accountability Act (HIPAA), reported in March 2020 that it will not impose penalties for not complying with HIPAA requirements on clinicians who provide good-faith telepsychiatry during the COVID-19 crisis.²

Clinicians who want to use audio or video remote communication to provide any type of telehealth services (not just those related to COVID-19) should use “non-public facing” products.² Non-public facing products (eg, Skype, WhatsApp video call, Zoom) allow only the intended parties to participate in the communication.³ Usually, these products employ end-to-end encryption, which allows only those engaging in communication to see and hear what is transmitted.³ To limit access and verify the participants, these products also support individual user accounts, login names, and passwords.³ In addition, these products usually allow participants and/or “the host” to exert some degree of control over particular features, such as choosing to record the communication, mute, or turn off the video or audio signal.³ When using these products, clinicians should enable all available encryption and privacy modes.²

“Public-facing” products (eg, Facebook Live, TikTok, Twitch) should not be used to provide telepsychiatry services because they are designed to be open to the public or allow for wide or indiscriminate access to the communication.^2,3 Clinicians who desire additional privacy protections (and a more permanent solution) should choose a HIPAA-compliant telehealth vendor (eg, Doxy.me, VSee, Zoom for Healthcare) and obtain a Business Associate Agreement with the vendor to ensure data protection and security.^2,4

Regardless of the product, obtain informed consent from your patients that authorizes the use of remote communication.⁴ Inform your patients of any potential privacy or security breaches, the need for interactions to be conducted in a location that provides privacy, and whether the specific technology used is HIPAA-compliant.⁴ Document that your patients understand these issues before using remote communication.⁴

How licensing requirements have changed

As of March 31, 2020, the CMS temporarily waived the requirement that out-of-state clinicians be licensed in the state where they are providing services to Medicare beneficiaries.⁵ The CMS waived this requirement for clinicians who meet the following 4 conditions^5,6:

• must be enrolled in Medicare
• must possess a valid license to practice in the state that relates to his/her Medicare enrollment
• are furnishing services—whether in person or via telepsychiatry—in a state where the emergency is occurring to contribute to relief efforts in his/her professional capacity
• are not excluded from practicing in any state that is part of the nationally declared emergency area.

Note that individual state licensure requirements continue to apply unless waived by the state.⁶ Therefore, in order for clinicians to see Medicare patients via remote communication under the 4 conditions described above, the state also would have to waive its licensure requirements for the type of practice for which the clinicians are licensed in their own state.⁶ Regarding commercial payers, in general, clinicians providing telepsychiatry services need a license to practice in the state where the patient is located at the time services are provided.⁶ During the COVID-19 pandemic, many governors issued executive orders waiving licensure requirements, and many have accelerated granting temporary licenses to out-of-state clinicians who wish to provide telepsychiatry services to the residents of their state.⁴

Continue to: Prescribing via telepsychiatry

 

 

Prescribing via telepsychiatry

Effective March 31, 2020 and lasting for the duration of COVID-19 emergency declaration, the Drug Enforcement Agency (DEA) suspended the Ryan Haight Online Pharmacy Consumer Protection Act of 2008, which requires clinicians to conduct initial, in-person examinations of patients before they can prescribe controlled substances electronically.^6,7 The DEA suspension allows clinicians to prescribe controlled substances after conducting an initial evaluation via remote communication. In addition, the DEA waived the requirement that a clinician needs to hold a DEA license in the state where the patient is located to be able to prescribe a controlled substance electronically.^4,6 However, you still must comply with all other state laws and regulations for prescribing controlled substances.⁴

Staying informed

Although several telepsychiatry rules and regulations have been modified or suspended during the COVID-19 pandemic, the standard of care for services rendered via telepsychiatry remains the same as services provided via face-to-face encounters, including patient evaluation and assessment, treatment plans, medication, and documentation.⁴ Clinicians can keep up-to-date on how practicing telepsychiatry may evolve during these times by using the following resources from the American Psychiatric Association:

• Telepsychiatry Toolkit: www.psychiatry.org/psychiatrists/practice/telepsychiatry
• Practice Guidance for COVID-19: www.psychiatry.org/psychiatrists/covid-19-coronavirus/practice-guidance-for-covid-19.

In addition to affecting our personal lives, coronavirus disease 2019 (COVID-19) has altered the way we practice psychiatry. Telepsychiatry—the delivery of mental health services via remote communication—is being used to replace face-to-face outpatient encounters. Several rules and regulations governing the provision of care and prescribing have been temporarily modified or suspended to allow clinicians to more easily use telepsychiatry to care for their patients. Although these requirements are continually changing, here I review some of the telepsychiatry rules and regulations clinicians need to understand to minimize their risk for liability.

Changes in light of COVID-19

In March 2020, the Centers for Medicare & Medicaid Services (CMS) released guidance that allows Medicare beneficiaries to receive various services at home through telehealth without having to travel to a doctor’s office or hospital.¹ Many commercial insurers also are allowing patients to receive telehealth services in their home. The US Department of Health & Human Services Office for Civil Rights, which enforces the Health Insurance Portability and Accountability Act (HIPAA), reported in March 2020 that it will not impose penalties for not complying with HIPAA requirements on clinicians who provide good-faith telepsychiatry during the COVID-19 crisis.²

Clinicians who want to use audio or video remote communication to provide any type of telehealth services (not just those related to COVID-19) should use “non-public facing” products.² Non-public facing products (eg, Skype, WhatsApp video call, Zoom) allow only the intended parties to participate in the communication.³ Usually, these products employ end-to-end encryption, which allows only those engaging in communication to see and hear what is transmitted.³ To limit access and verify the participants, these products also support individual user accounts, login names, and passwords.³ In addition, these products usually allow participants and/or “the host” to exert some degree of control over particular features, such as choosing to record the communication, mute, or turn off the video or audio signal.³ When using these products, clinicians should enable all available encryption and privacy modes.²

“Public-facing” products (eg, Facebook Live, TikTok, Twitch) should not be used to provide telepsychiatry services because they are designed to be open to the public or allow for wide or indiscriminate access to the communication.^2,3 Clinicians who desire additional privacy protections (and a more permanent solution) should choose a HIPAA-compliant telehealth vendor (eg, Doxy.me, VSee, Zoom for Healthcare) and obtain a Business Associate Agreement with the vendor to ensure data protection and security.^2,4

Regardless of the product, obtain informed consent from your patients that authorizes the use of remote communication.⁴ Inform your patients of any potential privacy or security breaches, the need for interactions to be conducted in a location that provides privacy, and whether the specific technology used is HIPAA-compliant.⁴ Document that your patients understand these issues before using remote communication.⁴

How licensing requirements have changed

As of March 31, 2020, the CMS temporarily waived the requirement that out-of-state clinicians be licensed in the state where they are providing services to Medicare beneficiaries.⁵ The CMS waived this requirement for clinicians who meet the following 4 conditions^5,6:

• must be enrolled in Medicare
• must possess a valid license to practice in the state that relates to his/her Medicare enrollment
• are furnishing services—whether in person or via telepsychiatry—in a state where the emergency is occurring to contribute to relief efforts in his/her professional capacity
• are not excluded from practicing in any state that is part of the nationally declared emergency area.

Note that individual state licensure requirements continue to apply unless waived by the state.⁶ Therefore, in order for clinicians to see Medicare patients via remote communication under the 4 conditions described above, the state also would have to waive its licensure requirements for the type of practice for which the clinicians are licensed in their own state.⁶ Regarding commercial payers, in general, clinicians providing telepsychiatry services need a license to practice in the state where the patient is located at the time services are provided.⁶ During the COVID-19 pandemic, many governors issued executive orders waiving licensure requirements, and many have accelerated granting temporary licenses to out-of-state clinicians who wish to provide telepsychiatry services to the residents of their state.⁴

Continue to: Prescribing via telepsychiatry

 

 

Prescribing via telepsychiatry

Effective March 31, 2020 and lasting for the duration of COVID-19 emergency declaration, the Drug Enforcement Agency (DEA) suspended the Ryan Haight Online Pharmacy Consumer Protection Act of 2008, which requires clinicians to conduct initial, in-person examinations of patients before they can prescribe controlled substances electronically.^6,7 The DEA suspension allows clinicians to prescribe controlled substances after conducting an initial evaluation via remote communication. In addition, the DEA waived the requirement that a clinician needs to hold a DEA license in the state where the patient is located to be able to prescribe a controlled substance electronically.^4,6 However, you still must comply with all other state laws and regulations for prescribing controlled substances.⁴

Staying informed

Although several telepsychiatry rules and regulations have been modified or suspended during the COVID-19 pandemic, the standard of care for services rendered via telepsychiatry remains the same as services provided via face-to-face encounters, including patient evaluation and assessment, treatment plans, medication, and documentation.⁴ Clinicians can keep up-to-date on how practicing telepsychiatry may evolve during these times by using the following resources from the American Psychiatric Association:

• Telepsychiatry Toolkit: www.psychiatry.org/psychiatrists/practice/telepsychiatry
• Practice Guidance for COVID-19: www.psychiatry.org/psychiatrists/covid-19-coronavirus/practice-guidance-for-covid-19.

In addition to affecting our personal lives, coronavirus disease 2019 (COVID-19) has altered the way we practice psychiatry. Telepsychiatry—the delivery of mental health services via remote communication—is being used to replace face-to-face outpatient encounters. Several rules and regulations governing the provision of care and prescribing have been temporarily modified or suspended to allow clinicians to more easily use telepsychiatry to care for their patients. Although these requirements are continually changing, here I review some of the telepsychiatry rules and regulations clinicians need to understand to minimize their risk for liability.

Changes in light of COVID-19

In March 2020, the Centers for Medicare & Medicaid Services (CMS) released guidance that allows Medicare beneficiaries to receive various services at home through telehealth without having to travel to a doctor’s office or hospital.¹ Many commercial insurers also are allowing patients to receive telehealth services in their home. The US Department of Health & Human Services Office for Civil Rights, which enforces the Health Insurance Portability and Accountability Act (HIPAA), reported in March 2020 that it will not impose penalties for not complying with HIPAA requirements on clinicians who provide good-faith telepsychiatry during the COVID-19 crisis.²

Clinicians who want to use audio or video remote communication to provide any type of telehealth services (not just those related to COVID-19) should use “non-public facing” products.² Non-public facing products (eg, Skype, WhatsApp video call, Zoom) allow only the intended parties to participate in the communication.³ Usually, these products employ end-to-end encryption, which allows only those engaging in communication to see and hear what is transmitted.³ To limit access and verify the participants, these products also support individual user accounts, login names, and passwords.³ In addition, these products usually allow participants and/or “the host” to exert some degree of control over particular features, such as choosing to record the communication, mute, or turn off the video or audio signal.³ When using these products, clinicians should enable all available encryption and privacy modes.²

“Public-facing” products (eg, Facebook Live, TikTok, Twitch) should not be used to provide telepsychiatry services because they are designed to be open to the public or allow for wide or indiscriminate access to the communication.^2,3 Clinicians who desire additional privacy protections (and a more permanent solution) should choose a HIPAA-compliant telehealth vendor (eg, Doxy.me, VSee, Zoom for Healthcare) and obtain a Business Associate Agreement with the vendor to ensure data protection and security.^2,4

Regardless of the product, obtain informed consent from your patients that authorizes the use of remote communication.⁴ Inform your patients of any potential privacy or security breaches, the need for interactions to be conducted in a location that provides privacy, and whether the specific technology used is HIPAA-compliant.⁴ Document that your patients understand these issues before using remote communication.⁴

How licensing requirements have changed

As of March 31, 2020, the CMS temporarily waived the requirement that out-of-state clinicians be licensed in the state where they are providing services to Medicare beneficiaries.⁵ The CMS waived this requirement for clinicians who meet the following 4 conditions^5,6:

• must be enrolled in Medicare
• must possess a valid license to practice in the state that relates to his/her Medicare enrollment
• are furnishing services—whether in person or via telepsychiatry—in a state where the emergency is occurring to contribute to relief efforts in his/her professional capacity
• are not excluded from practicing in any state that is part of the nationally declared emergency area.

Note that individual state licensure requirements continue to apply unless waived by the state.⁶ Therefore, in order for clinicians to see Medicare patients via remote communication under the 4 conditions described above, the state also would have to waive its licensure requirements for the type of practice for which the clinicians are licensed in their own state.⁶ Regarding commercial payers, in general, clinicians providing telepsychiatry services need a license to practice in the state where the patient is located at the time services are provided.⁶ During the COVID-19 pandemic, many governors issued executive orders waiving licensure requirements, and many have accelerated granting temporary licenses to out-of-state clinicians who wish to provide telepsychiatry services to the residents of their state.⁴

Continue to: Prescribing via telepsychiatry

 

 

Prescribing via telepsychiatry

Effective March 31, 2020 and lasting for the duration of COVID-19 emergency declaration, the Drug Enforcement Agency (DEA) suspended the Ryan Haight Online Pharmacy Consumer Protection Act of 2008, which requires clinicians to conduct initial, in-person examinations of patients before they can prescribe controlled substances electronically.^6,7 The DEA suspension allows clinicians to prescribe controlled substances after conducting an initial evaluation via remote communication. In addition, the DEA waived the requirement that a clinician needs to hold a DEA license in the state where the patient is located to be able to prescribe a controlled substance electronically.^4,6 However, you still must comply with all other state laws and regulations for prescribing controlled substances.⁴

Staying informed

Although several telepsychiatry rules and regulations have been modified or suspended during the COVID-19 pandemic, the standard of care for services rendered via telepsychiatry remains the same as services provided via face-to-face encounters, including patient evaluation and assessment, treatment plans, medication, and documentation.⁴ Clinicians can keep up-to-date on how practicing telepsychiatry may evolve during these times by using the following resources from the American Psychiatric Association:

• Telepsychiatry Toolkit: www.psychiatry.org/psychiatrists/practice/telepsychiatry
• Practice Guidance for COVID-19: www.psychiatry.org/psychiatrists/covid-19-coronavirus/practice-guidance-for-covid-19.

Our world has radically changed during the coronavirus disease 2019 (COVID-19) crisis, and this impact has quickly transformed many lives. Whether you’re on the front lines of the COVID-19 pandemic or waiting in eager anticipation to return to practice, there is no denying that a few months ago we could never have imagined the health care and humanitarian crisis that is now before us. While we are united in our longing for a better time, we couldn’t be further apart socially and emotionally … and I’m not just talking about 6 feet.

One thing that has been truly striking to me is the silence. While experts have suggested there is a “silent pandemic” of mental illness on the horizon,¹ I’ve been struck by the actual silence that exists as we walk through our stores and neighborhoods. We’re not speaking to each other anymore; it’s almost as if we’re afraid to make eye contact with one another.

Humans are social creatures, and the isolation that many people are experiencing during this pandemic could have detrimental and lasting effects if we don’t take action. While I highly encourage and support efforts to employ social distancing and mitigate the spread of this illness, I’m increasingly concerned about another kind of truly silent pandemic brewing beneath the surface of the COVID-19 crisis. Even under the best conditions, many individuals with posttraumatic stress disorder, depression, anxiety, bipolar disorder, schizophrenia, and other psychiatric disorders may lack adequate social interaction and experience feelings of isolation. These individuals need connection—not silence.

What happens to people who already felt intense isolation before COVID-19 and may have had invaluable lifelines cut off during this time of social distancing? What about individuals with alcohol or substance use disorders, or families who are sheltered in place in unsafe or violent home conditions? How can they reach out in silence? How can we help?

Fostering human connection

To address this, we must actively work to engage our patients and communities. One simple way to help is to acknowledge the people you encounter. Yes, stay 6 feet apart, and wear appropriate personal protective equipment. However, it is still OK to smile and greet someone with a nod, a smile, or a “hello.” A genuine smile can still be seen in someone’s eyes. We need these types of human connection, perhaps now more than ever before. We need each other.

Most importantly, during this time, we need to be aware of individuals who are most at risk in this silent pandemic. We can offer our patients appointments via video conferencing. We can use texting, e-mail, social media, phone calls, and video conferencing to check in with our families, friends, and neighbors. We’re at war with a terrible foe, but let’s not let the human connection become collateral damage.

Our world has radically changed during the coronavirus disease 2019 (COVID-19) crisis, and this impact has quickly transformed many lives. Whether you’re on the front lines of the COVID-19 pandemic or waiting in eager anticipation to return to practice, there is no denying that a few months ago we could never have imagined the health care and humanitarian crisis that is now before us. While we are united in our longing for a better time, we couldn’t be further apart socially and emotionally … and I’m not just talking about 6 feet.

One thing that has been truly striking to me is the silence. While experts have suggested there is a “silent pandemic” of mental illness on the horizon,¹ I’ve been struck by the actual silence that exists as we walk through our stores and neighborhoods. We’re not speaking to each other anymore; it’s almost as if we’re afraid to make eye contact with one another.

Humans are social creatures, and the isolation that many people are experiencing during this pandemic could have detrimental and lasting effects if we don’t take action. While I highly encourage and support efforts to employ social distancing and mitigate the spread of this illness, I’m increasingly concerned about another kind of truly silent pandemic brewing beneath the surface of the COVID-19 crisis. Even under the best conditions, many individuals with posttraumatic stress disorder, depression, anxiety, bipolar disorder, schizophrenia, and other psychiatric disorders may lack adequate social interaction and experience feelings of isolation. These individuals need connection—not silence.

What happens to people who already felt intense isolation before COVID-19 and may have had invaluable lifelines cut off during this time of social distancing? What about individuals with alcohol or substance use disorders, or families who are sheltered in place in unsafe or violent home conditions? How can they reach out in silence? How can we help?

Fostering human connection

To address this, we must actively work to engage our patients and communities. One simple way to help is to acknowledge the people you encounter. Yes, stay 6 feet apart, and wear appropriate personal protective equipment. However, it is still OK to smile and greet someone with a nod, a smile, or a “hello.” A genuine smile can still be seen in someone’s eyes. We need these types of human connection, perhaps now more than ever before. We need each other.

Most importantly, during this time, we need to be aware of individuals who are most at risk in this silent pandemic. We can offer our patients appointments via video conferencing. We can use texting, e-mail, social media, phone calls, and video conferencing to check in with our families, friends, and neighbors. We’re at war with a terrible foe, but let’s not let the human connection become collateral damage.

Our world has radically changed during the coronavirus disease 2019 (COVID-19) crisis, and this impact has quickly transformed many lives. Whether you’re on the front lines of the COVID-19 pandemic or waiting in eager anticipation to return to practice, there is no denying that a few months ago we could never have imagined the health care and humanitarian crisis that is now before us. While we are united in our longing for a better time, we couldn’t be further apart socially and emotionally … and I’m not just talking about 6 feet.

One thing that has been truly striking to me is the silence. While experts have suggested there is a “silent pandemic” of mental illness on the horizon,¹ I’ve been struck by the actual silence that exists as we walk through our stores and neighborhoods. We’re not speaking to each other anymore; it’s almost as if we’re afraid to make eye contact with one another.

Humans are social creatures, and the isolation that many people are experiencing during this pandemic could have detrimental and lasting effects if we don’t take action. While I highly encourage and support efforts to employ social distancing and mitigate the spread of this illness, I’m increasingly concerned about another kind of truly silent pandemic brewing beneath the surface of the COVID-19 crisis. Even under the best conditions, many individuals with posttraumatic stress disorder, depression, anxiety, bipolar disorder, schizophrenia, and other psychiatric disorders may lack adequate social interaction and experience feelings of isolation. These individuals need connection—not silence.

What happens to people who already felt intense isolation before COVID-19 and may have had invaluable lifelines cut off during this time of social distancing? What about individuals with alcohol or substance use disorders, or families who are sheltered in place in unsafe or violent home conditions? How can they reach out in silence? How can we help?

Fostering human connection

To address this, we must actively work to engage our patients and communities. One simple way to help is to acknowledge the people you encounter. Yes, stay 6 feet apart, and wear appropriate personal protective equipment. However, it is still OK to smile and greet someone with a nod, a smile, or a “hello.” A genuine smile can still be seen in someone’s eyes. We need these types of human connection, perhaps now more than ever before. We need each other.

Most importantly, during this time, we need to be aware of individuals who are most at risk in this silent pandemic. We can offer our patients appointments via video conferencing. We can use texting, e-mail, social media, phone calls, and video conferencing to check in with our families, friends, and neighbors. We’re at war with a terrible foe, but let’s not let the human connection become collateral damage.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

 

 

Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

 

 

Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

 

 

Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Are ACE inhibitors protective in COVID-19?

Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.

READ MORE.

AMI: Admissions drop, deaths rise

In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.

READ MORE.

Prenatal, postpartum screening for depression falls short

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

READ MORE.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Although the US Food and Drug Administration (FDA) has granted emergency use authorization of remdesivir (Gilead Sciences, Inc., Foster City, California) to treat COVID-19, the disease caused by SARS-CoV-2, the drug is considered an investigational agent, not yet formally approved by the FDA and whose efficacy and safety has not yet been fully characterized. Remdesivir has been shown to be effective in reducing the time to recovery of people with COVID-19 disease. It has not been tested in a large controlled clinical trial of pregnant women with COVID-19; however, remdesivir has been given to pregnant women infected with COVID-19 in a compassionate use protocol. For pregnant women, the drug should only be used if the potential benefit justifies the potential risk to the mother and fetus.¹

Pharmacology. Remdesivir is a nucleoside RNA polymerase inhibitor. It has a molecular formula of
C₂₇H₃₅N₆O₈P and a molecular weight of 602.6 g/mol.¹

Mechanism of action. From FDA’s fact sheet: “Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.”¹

Treatment protocols

Remdesivir is authorized for treatment of hospitalized patients with severe COVID-19 disease, defined as patients with an oxygen saturation ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). The optimal dose and duration of treatment of COVID-19 with remdesivir is unknown.¹

Prior to initiating treatment, the estimated glomerular filtration rate should be documented to be ≥ 30 mL/min. An excipient used in the remdesivir formulation—sulfobutylether-β-cylcodextrin sodium salt—is renally cleared and accumulates in patients with decreased renal function. 

Baseline liver function tests should be performed prior to treatment and daily during the course of treatment. Remdesivir should not be initiated in patients with an alanine aminotransferase (ALT) level ≥ 5 times the upper limit of normal at baseline. Remdesivir should be discontinued in patients who develop an ALT level ≥ 5 times the upper limit of normal or in patients who develop elevated ALT levels and have increased bilirubin, alkaline phosphatase, or international normalized ratio.¹

In one open-label study (GS-US-540-5773), remdesivir treatment was discontinued due to an adverse event in 5% of patients on a 5-day regimen and in 10% of patients on a 10-day regimen.¹

Under the emergency use authorization, two treatment protocols have been proposed depending on the clinical severity of the COVID-19 infection¹:

• Protocol 1: For people with COVID-19 requiring mechanical ventilation and/or ECMO, the duration of therapy is 10 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 9 days.
• Protocol 2: For people with COVID-19 disease not requiring mechanical ventilation and/or ECMO, the duration of therapy is 5 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 4 days. If the patient does not show clinical improvement, treatment may be extended for an additional 5 days. ​​​​​​

Continue to: Randomized placebo-controlled trial results...

Randomized placebo-controlled trial results

The Adaptive COVID-19 Treatment Trial (ACTT), sponsored by the National Institute of Allergy and Infectious Diseases, is a randomized, double-blind, placebo-controlled trial conducted by Gilead Sciences. The study began in February and evaluated up to 10 days of remdesivir treatment—200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days in hospitalized adult patients with COVID-19. Patients were enrolled in a 1:1 manner to remdesivir or placebo, and time to recovery within 28 days after randomization was the trial’s endpoint. According to preliminary analysis of 606 recovered patients, recovery took a median of 11 days in the remdesivir group and 15 days in the placebo group (hazard ratio, 1.31; 95% confidence interval (CI), 1.12‒1.54; P<.001). Mortality rates were 8.0% and 11.6% in the remdesivir and placebo groups, respectively (P=.059).¹

5 vs 10 days of remdesivir treatment

The Gilead Sciences‒sponsored study GS-US-540-5773 was a randomized, open-label multicenter trial of patients with severe COVID-19. A total of 197 adult patients received 10-day remdesivir treatment (200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days). An additional 200 adult patients received 5-day remdesivir treatment (200 mg IV once daily followed by 100 mg IV for 4 days). Both groups also received standard of care. Results suggested that patients receiving 10 days of remdesivir had similar improvement in clinical status compared with those receiving a 5-day treatment course (10-to-5 day odds ratio, 0.76; 95% CI, 0.51‒1.13] on day 14).¹ Improvement in clinical status was defined as an improvement of 2 or more points from baseline on a predefined 7-point scale that ranged from hospital discharge to increasing levels of oxygen support to death. Clinical recovery was achieved if patients ceased the need for oxygen support or were discharged.¹

The time to clinical improvement for 50% of patients was similar in each treatment group (10 days in the 5-day group versus 11 days in the 10-day group). By day 14, observed clinical improvement rates were 65% and 54% in the 5- and 10-day treatment groups, respectively. Clinical recovery rates were 70% and 59% in the 5- and 10-day treatment groups and mortality rates were 8% and 11%.¹

Adverse events

The use of remdesivir is contraindicated in patients who are hypersensitive to the drug. Its infusion may cause hypotension, nausea, vomiting, diaphoresis, and shivering. If signs of a clinically significant infusion reaction are observed the infusion should be discontinued. As noted above, elevation in ALT levels occurs with remdesivir treatment.¹

Reporting serious adverse events. If a serious and unexpected adverse event occurs and appears to be associated with the use of remdesivir, the prescribing health care provider and/or the provider’s designee should complete and submit a MedWatch form to the FDA using one of the following methods¹:

• Complete and submit the report online: www.fda.gov/medwatch/report.htm
• Return form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) to the FDA by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787) or fax (1-800-FDA-0178)
• Gilead requests that all FDA MedWatch forms also be returned to Gilead Pharmacovigilance and Epidemiology: fax: 1-650-522-5477 726; e-mail: Safety_fc@gilead.com

Continue to: Drug interactions...

Drug interactions

Remdesivir has not been evaluated for drug-drug interactions in humans. The clinical relevance of in vitro drug interactions also has not been established. According to the FDA, remdesivir is a substrate for the drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for organic anion transporting polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir inhibits CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP.¹

Pregnancy risk summary

Remdesivir has not been studied adequately in pregnant women and only should be used during pregnancy if the potential benefit of the drug justifies the potential risk to both mother and fetus.

Nonclinical animal studies that included systemic exposure of the predominant circulating metabolite of remdesivir in pregnant rats and rabbits (at 4 times the recommended dose of human exposure) demonstrated no adverse effect on embryofetal development.¹

Breastfeeding

The only information regarding breastfeeding and remdesivir comes from animal studies. The drug and its metabolites were detected in the plasma of nursing rat pups whose mothers given intravenous remdesivir daily from gestation day 6 to lactation day 20. Measured on lactation day 10, remdesivir exposure in the pups was about 1% that of maternal exposure.¹

“Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.”¹

Although the US Food and Drug Administration (FDA) has granted emergency use authorization of remdesivir (Gilead Sciences, Inc., Foster City, California) to treat COVID-19, the disease caused by SARS-CoV-2, the drug is considered an investigational agent, not yet formally approved by the FDA and whose efficacy and safety has not yet been fully characterized. Remdesivir has been shown to be effective in reducing the time to recovery of people with COVID-19 disease. It has not been tested in a large controlled clinical trial of pregnant women with COVID-19; however, remdesivir has been given to pregnant women infected with COVID-19 in a compassionate use protocol. For pregnant women, the drug should only be used if the potential benefit justifies the potential risk to the mother and fetus.¹

Pharmacology. Remdesivir is a nucleoside RNA polymerase inhibitor. It has a molecular formula of
C₂₇H₃₅N₆O₈P and a molecular weight of 602.6 g/mol.¹

Mechanism of action. From FDA’s fact sheet: “Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.”¹

Treatment protocols

Remdesivir is authorized for treatment of hospitalized patients with severe COVID-19 disease, defined as patients with an oxygen saturation ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). The optimal dose and duration of treatment of COVID-19 with remdesivir is unknown.¹

Prior to initiating treatment, the estimated glomerular filtration rate should be documented to be ≥ 30 mL/min. An excipient used in the remdesivir formulation—sulfobutylether-β-cylcodextrin sodium salt—is renally cleared and accumulates in patients with decreased renal function. 

Baseline liver function tests should be performed prior to treatment and daily during the course of treatment. Remdesivir should not be initiated in patients with an alanine aminotransferase (ALT) level ≥ 5 times the upper limit of normal at baseline. Remdesivir should be discontinued in patients who develop an ALT level ≥ 5 times the upper limit of normal or in patients who develop elevated ALT levels and have increased bilirubin, alkaline phosphatase, or international normalized ratio.¹

In one open-label study (GS-US-540-5773), remdesivir treatment was discontinued due to an adverse event in 5% of patients on a 5-day regimen and in 10% of patients on a 10-day regimen.¹

Under the emergency use authorization, two treatment protocols have been proposed depending on the clinical severity of the COVID-19 infection¹:

• Protocol 1: For people with COVID-19 requiring mechanical ventilation and/or ECMO, the duration of therapy is 10 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 9 days.
• Protocol 2: For people with COVID-19 disease not requiring mechanical ventilation and/or ECMO, the duration of therapy is 5 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 4 days. If the patient does not show clinical improvement, treatment may be extended for an additional 5 days. ​​​​​​

Continue to: Randomized placebo-controlled trial results...

Randomized placebo-controlled trial results

The Adaptive COVID-19 Treatment Trial (ACTT), sponsored by the National Institute of Allergy and Infectious Diseases, is a randomized, double-blind, placebo-controlled trial conducted by Gilead Sciences. The study began in February and evaluated up to 10 days of remdesivir treatment—200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days in hospitalized adult patients with COVID-19. Patients were enrolled in a 1:1 manner to remdesivir or placebo, and time to recovery within 28 days after randomization was the trial’s endpoint. According to preliminary analysis of 606 recovered patients, recovery took a median of 11 days in the remdesivir group and 15 days in the placebo group (hazard ratio, 1.31; 95% confidence interval (CI), 1.12‒1.54; P<.001). Mortality rates were 8.0% and 11.6% in the remdesivir and placebo groups, respectively (P=.059).¹

5 vs 10 days of remdesivir treatment

The Gilead Sciences‒sponsored study GS-US-540-5773 was a randomized, open-label multicenter trial of patients with severe COVID-19. A total of 197 adult patients received 10-day remdesivir treatment (200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days). An additional 200 adult patients received 5-day remdesivir treatment (200 mg IV once daily followed by 100 mg IV for 4 days). Both groups also received standard of care. Results suggested that patients receiving 10 days of remdesivir had similar improvement in clinical status compared with those receiving a 5-day treatment course (10-to-5 day odds ratio, 0.76; 95% CI, 0.51‒1.13] on day 14).¹ Improvement in clinical status was defined as an improvement of 2 or more points from baseline on a predefined 7-point scale that ranged from hospital discharge to increasing levels of oxygen support to death. Clinical recovery was achieved if patients ceased the need for oxygen support or were discharged.¹

The time to clinical improvement for 50% of patients was similar in each treatment group (10 days in the 5-day group versus 11 days in the 10-day group). By day 14, observed clinical improvement rates were 65% and 54% in the 5- and 10-day treatment groups, respectively. Clinical recovery rates were 70% and 59% in the 5- and 10-day treatment groups and mortality rates were 8% and 11%.¹

Adverse events

The use of remdesivir is contraindicated in patients who are hypersensitive to the drug. Its infusion may cause hypotension, nausea, vomiting, diaphoresis, and shivering. If signs of a clinically significant infusion reaction are observed the infusion should be discontinued. As noted above, elevation in ALT levels occurs with remdesivir treatment.¹

Reporting serious adverse events. If a serious and unexpected adverse event occurs and appears to be associated with the use of remdesivir, the prescribing health care provider and/or the provider’s designee should complete and submit a MedWatch form to the FDA using one of the following methods¹:

• Complete and submit the report online: www.fda.gov/medwatch/report.htm
• Return form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) to the FDA by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787) or fax (1-800-FDA-0178)
• Gilead requests that all FDA MedWatch forms also be returned to Gilead Pharmacovigilance and Epidemiology: fax: 1-650-522-5477 726; e-mail: Safety_fc@gilead.com

Continue to: Drug interactions...

Drug interactions

Remdesivir has not been evaluated for drug-drug interactions in humans. The clinical relevance of in vitro drug interactions also has not been established. According to the FDA, remdesivir is a substrate for the drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for organic anion transporting polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir inhibits CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP.¹

Pregnancy risk summary

Remdesivir has not been studied adequately in pregnant women and only should be used during pregnancy if the potential benefit of the drug justifies the potential risk to both mother and fetus.

Nonclinical animal studies that included systemic exposure of the predominant circulating metabolite of remdesivir in pregnant rats and rabbits (at 4 times the recommended dose of human exposure) demonstrated no adverse effect on embryofetal development.¹

Breastfeeding

The only information regarding breastfeeding and remdesivir comes from animal studies. The drug and its metabolites were detected in the plasma of nursing rat pups whose mothers given intravenous remdesivir daily from gestation day 6 to lactation day 20. Measured on lactation day 10, remdesivir exposure in the pups was about 1% that of maternal exposure.¹

“Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.”¹

Although the US Food and Drug Administration (FDA) has granted emergency use authorization of remdesivir (Gilead Sciences, Inc., Foster City, California) to treat COVID-19, the disease caused by SARS-CoV-2, the drug is considered an investigational agent, not yet formally approved by the FDA and whose efficacy and safety has not yet been fully characterized. Remdesivir has been shown to be effective in reducing the time to recovery of people with COVID-19 disease. It has not been tested in a large controlled clinical trial of pregnant women with COVID-19; however, remdesivir has been given to pregnant women infected with COVID-19 in a compassionate use protocol. For pregnant women, the drug should only be used if the potential benefit justifies the potential risk to the mother and fetus.¹

Pharmacology. Remdesivir is a nucleoside RNA polymerase inhibitor. It has a molecular formula of
C₂₇H₃₅N₆O₈P and a molecular weight of 602.6 g/mol.¹

Mechanism of action. From FDA’s fact sheet: “Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.”¹

Treatment protocols

Remdesivir is authorized for treatment of hospitalized patients with severe COVID-19 disease, defined as patients with an oxygen saturation ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). The optimal dose and duration of treatment of COVID-19 with remdesivir is unknown.¹

Prior to initiating treatment, the estimated glomerular filtration rate should be documented to be ≥ 30 mL/min. An excipient used in the remdesivir formulation—sulfobutylether-β-cylcodextrin sodium salt—is renally cleared and accumulates in patients with decreased renal function. 

Baseline liver function tests should be performed prior to treatment and daily during the course of treatment. Remdesivir should not be initiated in patients with an alanine aminotransferase (ALT) level ≥ 5 times the upper limit of normal at baseline. Remdesivir should be discontinued in patients who develop an ALT level ≥ 5 times the upper limit of normal or in patients who develop elevated ALT levels and have increased bilirubin, alkaline phosphatase, or international normalized ratio.¹

In one open-label study (GS-US-540-5773), remdesivir treatment was discontinued due to an adverse event in 5% of patients on a 5-day regimen and in 10% of patients on a 10-day regimen.¹

Under the emergency use authorization, two treatment protocols have been proposed depending on the clinical severity of the COVID-19 infection¹:

• Protocol 1: For people with COVID-19 requiring mechanical ventilation and/or ECMO, the duration of therapy is 10 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 9 days.
• Protocol 2: For people with COVID-19 disease not requiring mechanical ventilation and/or ECMO, the duration of therapy is 5 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 4 days. If the patient does not show clinical improvement, treatment may be extended for an additional 5 days. ​​​​​​

Continue to: Randomized placebo-controlled trial results...

Randomized placebo-controlled trial results

The Adaptive COVID-19 Treatment Trial (ACTT), sponsored by the National Institute of Allergy and Infectious Diseases, is a randomized, double-blind, placebo-controlled trial conducted by Gilead Sciences. The study began in February and evaluated up to 10 days of remdesivir treatment—200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days in hospitalized adult patients with COVID-19. Patients were enrolled in a 1:1 manner to remdesivir or placebo, and time to recovery within 28 days after randomization was the trial’s endpoint. According to preliminary analysis of 606 recovered patients, recovery took a median of 11 days in the remdesivir group and 15 days in the placebo group (hazard ratio, 1.31; 95% confidence interval (CI), 1.12‒1.54; P<.001). Mortality rates were 8.0% and 11.6% in the remdesivir and placebo groups, respectively (P=.059).¹

5 vs 10 days of remdesivir treatment

The Gilead Sciences‒sponsored study GS-US-540-5773 was a randomized, open-label multicenter trial of patients with severe COVID-19. A total of 197 adult patients received 10-day remdesivir treatment (200 mg IV once daily for 1 day followed by 100 mg IV once daily for 9 days). An additional 200 adult patients received 5-day remdesivir treatment (200 mg IV once daily followed by 100 mg IV for 4 days). Both groups also received standard of care. Results suggested that patients receiving 10 days of remdesivir had similar improvement in clinical status compared with those receiving a 5-day treatment course (10-to-5 day odds ratio, 0.76; 95% CI, 0.51‒1.13] on day 14).¹ Improvement in clinical status was defined as an improvement of 2 or more points from baseline on a predefined 7-point scale that ranged from hospital discharge to increasing levels of oxygen support to death. Clinical recovery was achieved if patients ceased the need for oxygen support or were discharged.¹

The time to clinical improvement for 50% of patients was similar in each treatment group (10 days in the 5-day group versus 11 days in the 10-day group). By day 14, observed clinical improvement rates were 65% and 54% in the 5- and 10-day treatment groups, respectively. Clinical recovery rates were 70% and 59% in the 5- and 10-day treatment groups and mortality rates were 8% and 11%.¹

Adverse events

The use of remdesivir is contraindicated in patients who are hypersensitive to the drug. Its infusion may cause hypotension, nausea, vomiting, diaphoresis, and shivering. If signs of a clinically significant infusion reaction are observed the infusion should be discontinued. As noted above, elevation in ALT levels occurs with remdesivir treatment.¹

Reporting serious adverse events. If a serious and unexpected adverse event occurs and appears to be associated with the use of remdesivir, the prescribing health care provider and/or the provider’s designee should complete and submit a MedWatch form to the FDA using one of the following methods¹:

• Complete and submit the report online: www.fda.gov/medwatch/report.htm
• Return form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) to the FDA by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787) or fax (1-800-FDA-0178)
• Gilead requests that all FDA MedWatch forms also be returned to Gilead Pharmacovigilance and Epidemiology: fax: 1-650-522-5477 726; e-mail: Safety_fc@gilead.com

Continue to: Drug interactions...

Drug interactions

Remdesivir has not been evaluated for drug-drug interactions in humans. The clinical relevance of in vitro drug interactions also has not been established. According to the FDA, remdesivir is a substrate for the drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for organic anion transporting polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir inhibits CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP.¹

Pregnancy risk summary

Remdesivir has not been studied adequately in pregnant women and only should be used during pregnancy if the potential benefit of the drug justifies the potential risk to both mother and fetus.

Nonclinical animal studies that included systemic exposure of the predominant circulating metabolite of remdesivir in pregnant rats and rabbits (at 4 times the recommended dose of human exposure) demonstrated no adverse effect on embryofetal development.¹

Breastfeeding

The only information regarding breastfeeding and remdesivir comes from animal studies. The drug and its metabolites were detected in the plasma of nursing rat pups whose mothers given intravenous remdesivir daily from gestation day 6 to lactation day 20. Measured on lactation day 10, remdesivir exposure in the pups was about 1% that of maternal exposure.¹

“Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.”¹

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

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John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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