Pulmonology

Use of diffusing capacity of the lung for carbon monoxide may be a useful prognostic tool in patients with chronic pulmonary disease who develop pulmonary hypertension, results from a single-center retrospective cohort study found.

“Historically, COPD-PH was thought to develop as the severity of airflow obstruction, measured by Forced Expiratory Volume in one second (FEV₁), and subsequent chronic hypoxemia progressed,” authors led by Aparna Balasubramanian, MD, wrote in a study published online in CHEST. “However, airflow obstruction has increasingly been noted to be insufficient in predicting clinical outcomes in the general COPD population.”

Dr. Balasubramanian of the Johns Hopkins University Division of Pulmonary and Critical Care, Baltimore, and colleagues went on to note that, while studies in COPD-PH have identified hemodynamic measures as better predictors of prognosis, these metrics require right-heart catheterization (RHC), an invasive procedure that carries its own risks. “An alternative noninvasive measure of interest is diffusing capacity of the lung for carbon monoxide (DLCO). DLCO is a measure of gas exchange reflective of the complex interactions occurring at the alveolar-capillary interface, including morphologic changes in the pulmonary vasculature,” they wrote. “Recent work by our group in a large COPD cohort has demonstrated that DLCO is an indicator of disease morbidity beyond that represented by airflow obstruction or by CT evidence of emphysema alone. This may be particularly relevant for those with COPD-PH.”

The study population consisted of 71 patients enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and January 2018, all of whom had right-heart catheterization (RHC)–proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. The researchers calculated transplant-free survival from index RHC and used Cox proportional hazard methods to determine transplant-free survival with age, pulmonary vascular resistance, FEV₁, oxygen use, and N-terminal pro-brain natriuretic peptide included as covariates.

The average age of patients was 65 years, 66% were female, their average body mass index was 28.3 kg/m², and the mean number of pack-years smoked was 44. On unadjusted analysis, the transplant-free survival was 87% at 1 year, 60% at 3 years, and 51% at 5 years. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and pulmonary vascular resistance. The researchers found that severe DLCO impairment was associated with poorer survival (P less than .001), and when they adjusted for covariates, they found that mortality increased by 4% for every percent predicted decrease in DLCO (hazard ratio, 1.04).

“This study demonstrates that DLCO, a readily available, inexpensive, noninvasive measurement, is a strong independent predictor of mortality in COPD patients with PH,” the authors concluded. “The presented findings suggest that DLCO should be considered for inclusion in prognostic tools for COPD-PH.”

Dr. Balasubramanian and associates acknowledged certain limitations of the study, including its modest sample size and single-center design and the fact that the cohort underwent subspecialty referral and invasive testing, thereby limiting its generalizability to the larger COPD population. “The findings do, however, offer insight into clinical and physiologic characteristics at one extreme of the pulmonary vascular disease spectrum among COPD patients, and generate hypotheses regarding measures that warrant further exploration in the larger COPD population,” they wrote.

The study was supported by National Heart, Lung and Blood Institute. One of the study authors has served as a consultant to GlaxoSmithKline and Celgene and receives royalties from UpToDate for authorship. Another study author has served as a consultant for Arena, Actelion, Liquidia, and United Therapeutics, and has served on the Scientific Leadership Council of the Pulmonary Hypertension Association. He also serves on the Rare Disease Advisory Panel of the Patient Centered Outcomes Research Institute. The other study authors reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Balasubramanian A et al. CHEST. 2020 Mar 14. doi: 10.1016/j.chest.2020.02.047.

Use of diffusing capacity of the lung for carbon monoxide may be a useful prognostic tool in patients with chronic pulmonary disease who develop pulmonary hypertension, results from a single-center retrospective cohort study found.

“Historically, COPD-PH was thought to develop as the severity of airflow obstruction, measured by Forced Expiratory Volume in one second (FEV₁), and subsequent chronic hypoxemia progressed,” authors led by Aparna Balasubramanian, MD, wrote in a study published online in CHEST. “However, airflow obstruction has increasingly been noted to be insufficient in predicting clinical outcomes in the general COPD population.”

Dr. Balasubramanian of the Johns Hopkins University Division of Pulmonary and Critical Care, Baltimore, and colleagues went on to note that, while studies in COPD-PH have identified hemodynamic measures as better predictors of prognosis, these metrics require right-heart catheterization (RHC), an invasive procedure that carries its own risks. “An alternative noninvasive measure of interest is diffusing capacity of the lung for carbon monoxide (DLCO). DLCO is a measure of gas exchange reflective of the complex interactions occurring at the alveolar-capillary interface, including morphologic changes in the pulmonary vasculature,” they wrote. “Recent work by our group in a large COPD cohort has demonstrated that DLCO is an indicator of disease morbidity beyond that represented by airflow obstruction or by CT evidence of emphysema alone. This may be particularly relevant for those with COPD-PH.”

The study population consisted of 71 patients enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and January 2018, all of whom had right-heart catheterization (RHC)–proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. The researchers calculated transplant-free survival from index RHC and used Cox proportional hazard methods to determine transplant-free survival with age, pulmonary vascular resistance, FEV₁, oxygen use, and N-terminal pro-brain natriuretic peptide included as covariates.

The average age of patients was 65 years, 66% were female, their average body mass index was 28.3 kg/m², and the mean number of pack-years smoked was 44. On unadjusted analysis, the transplant-free survival was 87% at 1 year, 60% at 3 years, and 51% at 5 years. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and pulmonary vascular resistance. The researchers found that severe DLCO impairment was associated with poorer survival (P less than .001), and when they adjusted for covariates, they found that mortality increased by 4% for every percent predicted decrease in DLCO (hazard ratio, 1.04).

“This study demonstrates that DLCO, a readily available, inexpensive, noninvasive measurement, is a strong independent predictor of mortality in COPD patients with PH,” the authors concluded. “The presented findings suggest that DLCO should be considered for inclusion in prognostic tools for COPD-PH.”

Dr. Balasubramanian and associates acknowledged certain limitations of the study, including its modest sample size and single-center design and the fact that the cohort underwent subspecialty referral and invasive testing, thereby limiting its generalizability to the larger COPD population. “The findings do, however, offer insight into clinical and physiologic characteristics at one extreme of the pulmonary vascular disease spectrum among COPD patients, and generate hypotheses regarding measures that warrant further exploration in the larger COPD population,” they wrote.

The study was supported by National Heart, Lung and Blood Institute. One of the study authors has served as a consultant to GlaxoSmithKline and Celgene and receives royalties from UpToDate for authorship. Another study author has served as a consultant for Arena, Actelion, Liquidia, and United Therapeutics, and has served on the Scientific Leadership Council of the Pulmonary Hypertension Association. He also serves on the Rare Disease Advisory Panel of the Patient Centered Outcomes Research Institute. The other study authors reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Balasubramanian A et al. CHEST. 2020 Mar 14. doi: 10.1016/j.chest.2020.02.047.

Use of diffusing capacity of the lung for carbon monoxide may be a useful prognostic tool in patients with chronic pulmonary disease who develop pulmonary hypertension, results from a single-center retrospective cohort study found.

“Historically, COPD-PH was thought to develop as the severity of airflow obstruction, measured by Forced Expiratory Volume in one second (FEV₁), and subsequent chronic hypoxemia progressed,” authors led by Aparna Balasubramanian, MD, wrote in a study published online in CHEST. “However, airflow obstruction has increasingly been noted to be insufficient in predicting clinical outcomes in the general COPD population.”

Dr. Balasubramanian of the Johns Hopkins University Division of Pulmonary and Critical Care, Baltimore, and colleagues went on to note that, while studies in COPD-PH have identified hemodynamic measures as better predictors of prognosis, these metrics require right-heart catheterization (RHC), an invasive procedure that carries its own risks. “An alternative noninvasive measure of interest is diffusing capacity of the lung for carbon monoxide (DLCO). DLCO is a measure of gas exchange reflective of the complex interactions occurring at the alveolar-capillary interface, including morphologic changes in the pulmonary vasculature,” they wrote. “Recent work by our group in a large COPD cohort has demonstrated that DLCO is an indicator of disease morbidity beyond that represented by airflow obstruction or by CT evidence of emphysema alone. This may be particularly relevant for those with COPD-PH.”

The study population consisted of 71 patients enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and January 2018, all of whom had right-heart catheterization (RHC)–proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. The researchers calculated transplant-free survival from index RHC and used Cox proportional hazard methods to determine transplant-free survival with age, pulmonary vascular resistance, FEV₁, oxygen use, and N-terminal pro-brain natriuretic peptide included as covariates.

The average age of patients was 65 years, 66% were female, their average body mass index was 28.3 kg/m², and the mean number of pack-years smoked was 44. On unadjusted analysis, the transplant-free survival was 87% at 1 year, 60% at 3 years, and 51% at 5 years. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and pulmonary vascular resistance. The researchers found that severe DLCO impairment was associated with poorer survival (P less than .001), and when they adjusted for covariates, they found that mortality increased by 4% for every percent predicted decrease in DLCO (hazard ratio, 1.04).

“This study demonstrates that DLCO, a readily available, inexpensive, noninvasive measurement, is a strong independent predictor of mortality in COPD patients with PH,” the authors concluded. “The presented findings suggest that DLCO should be considered for inclusion in prognostic tools for COPD-PH.”

Dr. Balasubramanian and associates acknowledged certain limitations of the study, including its modest sample size and single-center design and the fact that the cohort underwent subspecialty referral and invasive testing, thereby limiting its generalizability to the larger COPD population. “The findings do, however, offer insight into clinical and physiologic characteristics at one extreme of the pulmonary vascular disease spectrum among COPD patients, and generate hypotheses regarding measures that warrant further exploration in the larger COPD population,” they wrote.

The study was supported by National Heart, Lung and Blood Institute. One of the study authors has served as a consultant to GlaxoSmithKline and Celgene and receives royalties from UpToDate for authorship. Another study author has served as a consultant for Arena, Actelion, Liquidia, and United Therapeutics, and has served on the Scientific Leadership Council of the Pulmonary Hypertension Association. He also serves on the Rare Disease Advisory Panel of the Patient Centered Outcomes Research Institute. The other study authors reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Balasubramanian A et al. CHEST. 2020 Mar 14. doi: 10.1016/j.chest.2020.02.047.

A research team at Vanderbilt University Medical Center has begun a trial to compare the value of tracking daily activity and the Six Minute Walk Distance to predict pulmonary hypertension prognosis. The Longitudinal Pulmonary Vascular Disease Phenomics Program (L-PVDOMICS), a prospective, longitudinal, observational study will track daily activity and patient-reported outcomes in participants enrolled. Patients with pulmonary hypertension and healthy participants will undergo activity monitoring for 12 weeks once a year for 4 years. Metrics will include patient-reported outcomes including quality of life (emphasis-10, Minnesota Living with Heart Failure, and SF-36 surveys), medication changes, hospitalization, and death.

The study is designed to establish the clinical utility of daily activity tracking in patients with pulmonary hypertension and to identify clinical factors associated with reduced daily activity. Five hundred patients are expected to enroll and the estimated closing date is June 2023. The hypothesis for the study is that daily activity will have stronger prognostic value after 12 weeks than the Six Minute Walk Distance in patients with pulmonary hypertension. Participants will wear an accelerometer to record activity level to determine daily activities and will also engage in the Six Minute Walk Distance Test.

Individuals that are pregnant or have been hospitalized within the past 3 months will be excluded. Participants are currently being recruited.

The trial sponsor is Vanderbilt University Medical Center.

tborden@mdedge.com

A research team at Vanderbilt University Medical Center has begun a trial to compare the value of tracking daily activity and the Six Minute Walk Distance to predict pulmonary hypertension prognosis. The Longitudinal Pulmonary Vascular Disease Phenomics Program (L-PVDOMICS), a prospective, longitudinal, observational study will track daily activity and patient-reported outcomes in participants enrolled. Patients with pulmonary hypertension and healthy participants will undergo activity monitoring for 12 weeks once a year for 4 years. Metrics will include patient-reported outcomes including quality of life (emphasis-10, Minnesota Living with Heart Failure, and SF-36 surveys), medication changes, hospitalization, and death.

The study is designed to establish the clinical utility of daily activity tracking in patients with pulmonary hypertension and to identify clinical factors associated with reduced daily activity. Five hundred patients are expected to enroll and the estimated closing date is June 2023. The hypothesis for the study is that daily activity will have stronger prognostic value after 12 weeks than the Six Minute Walk Distance in patients with pulmonary hypertension. Participants will wear an accelerometer to record activity level to determine daily activities and will also engage in the Six Minute Walk Distance Test.

Individuals that are pregnant or have been hospitalized within the past 3 months will be excluded. Participants are currently being recruited.

The trial sponsor is Vanderbilt University Medical Center.

tborden@mdedge.com

A research team at Vanderbilt University Medical Center has begun a trial to compare the value of tracking daily activity and the Six Minute Walk Distance to predict pulmonary hypertension prognosis. The Longitudinal Pulmonary Vascular Disease Phenomics Program (L-PVDOMICS), a prospective, longitudinal, observational study will track daily activity and patient-reported outcomes in participants enrolled. Patients with pulmonary hypertension and healthy participants will undergo activity monitoring for 12 weeks once a year for 4 years. Metrics will include patient-reported outcomes including quality of life (emphasis-10, Minnesota Living with Heart Failure, and SF-36 surveys), medication changes, hospitalization, and death.

The study is designed to establish the clinical utility of daily activity tracking in patients with pulmonary hypertension and to identify clinical factors associated with reduced daily activity. Five hundred patients are expected to enroll and the estimated closing date is June 2023. The hypothesis for the study is that daily activity will have stronger prognostic value after 12 weeks than the Six Minute Walk Distance in patients with pulmonary hypertension. Participants will wear an accelerometer to record activity level to determine daily activities and will also engage in the Six Minute Walk Distance Test.

Individuals that are pregnant or have been hospitalized within the past 3 months will be excluded. Participants are currently being recruited.

The trial sponsor is Vanderbilt University Medical Center.

tborden@mdedge.com

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

The COVID-19 pandemic is already affecting mental health at a population level, with increased anxiety, feelings of isolation, and concerns about access to mental health care.

Two U.K. surveys were conducted to inform research priorities for mental health research and in an effort to head off a mental health crisis. The U.K. charity MQ conducted a “stakeholder” survey of 2,198 individuals who had a lived experience of mental illness, while Ipsos MORI conducted a poll of 1,099 members of the public.

The online surveys were conducted in late March, the same week the U.K.’s nationwide lockdown measures were announced. Respondents were asked about their biggest mental health and well-being concerns and coping strategies as they relate to the COVID-19 pandemic.

Results showed that across the two surveys, respondents’ primary concern was anxiety, which was cited in 750 responses. Reported symptoms included overthinking, crying, nausea, heart palpitations, sleep disturbance, and a sense of guilt about not knowing how to help others.

In addition, respondents were worried about being social isolated, becoming mentally unwell, and having a lack of access to mental health services, as well as the impact of the pandemic on personal relationships.

The findings were used by a panel of experts to inform a position paper published in the Lancet Psychiatry. The paper outlines a proposed government response to curb the long-term “profound” and “pervasive” impact of the pandemic on mental health.
 

‘Unprecedented response’ needed

“Governments must find evidence-based ways to boost the resilience of our societies and ... to treat those with mental ill health remotely to come out of this pandemic in good mental health,” coauthor of the paper Emily A. Holmes, PhD, of the department of psychology at Uppsala (Sweden) University, said in a press release.

“Frontline medical staff and vulnerable groups such as the elderly and those with serious mental health conditions must be prioritized for rapid mental health support,” she added.

The position paper authors call for “moment-to-moment” monitoring of anxiety, depression, self-harm, and suicide, as well as using digital technology and rapid deployment of evidence-based programs and treatments.

Patients will need to be accessible via computer, cell phone, and other remote technologies in order to receive treatment during physical isolation. However, they noted that there is no “one-size-fits-all” approach, and novel approaches custom tailored to particular populations, including frontline health care workers, are necessary.

“To make a real difference we will need to harness the tools of our digital age, finding smart new ways to measure the mental health of individuals remotely, finding creative ways to boost resilience, and finding ways to treat people in their homes. This effort must be considered central to our global response to the pandemic,” coauthor Ed Bullmore, PhD, of the department of psychiatry at the University of Cambridge (England), said in a statement.

Dr. Bullmore added that it will take “unprecedented research response if we are to limit the negative consequences of this pandemic on the mental health of our society now and in the future.”
 

Most vulnerable will bear the brunt

During a webinar held to discuss the paper, Matthew Hotopf, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London, cautioned that society’s most vulnerable citizens will bear the brunt of the pandemic’s mental health consequences.

“These individuals often have unstable housing, unstable work, and are disadvantaged in terms of their physical health and their mental health,” with a “very significant gap” in life expectancy versus the rest of the population, he said. The COVID-19 pandemic will widen the gap between “the haves and the have nots.”

“People with established and significant mental disorders are one version of the ‘have nots’ but actually it applies to a lot of people,” said Dr. Hotopf, noting that his experience of lockdown is “very different” from that of someone “living in overcrowded, unstable accommodation, with kids running around and maybe a partner who has problems with anger control.”

The authors of the position paper noted that the COVID-19 pandemic highlights several important research priorities that need to be addressed in the coming weeks and months. These include:

• Understanding the effect of COVID-19 on risk of anxiety, depression, and other outcomes, such as self-harm and suicide
• Understanding how to create physical and social supports to ensure mental health in a climate of physical distancing
• Determining the mental health consequences of social isolation for vulnerable groups, and how can these be mitigated under pandemic conditions
• Understanding the mental health impact of media reporting of COVID-19 in traditional and social media
• Determining the best methods for promoting successful adherence to behavioral advice about COVID-19 while enabling mental well-being and minimizing distress

Another area highlighted by the experts is the potential for neuropsychiatric sequelae in individuals infected with COVID-19. They called for “experimental medicine studies to validate clinical biomarkers and repurpose new treatments for the potentially neurotoxic effects of the virus.”

The authors/investigators disclosed no relevant financial relationships.

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

The COVID-19 pandemic is already affecting mental health at a population level, with increased anxiety, feelings of isolation, and concerns about access to mental health care.

Two U.K. surveys were conducted to inform research priorities for mental health research and in an effort to head off a mental health crisis. The U.K. charity MQ conducted a “stakeholder” survey of 2,198 individuals who had a lived experience of mental illness, while Ipsos MORI conducted a poll of 1,099 members of the public.

The online surveys were conducted in late March, the same week the U.K.’s nationwide lockdown measures were announced. Respondents were asked about their biggest mental health and well-being concerns and coping strategies as they relate to the COVID-19 pandemic.

Results showed that across the two surveys, respondents’ primary concern was anxiety, which was cited in 750 responses. Reported symptoms included overthinking, crying, nausea, heart palpitations, sleep disturbance, and a sense of guilt about not knowing how to help others.

In addition, respondents were worried about being social isolated, becoming mentally unwell, and having a lack of access to mental health services, as well as the impact of the pandemic on personal relationships.

The findings were used by a panel of experts to inform a position paper published in the Lancet Psychiatry. The paper outlines a proposed government response to curb the long-term “profound” and “pervasive” impact of the pandemic on mental health.
 

‘Unprecedented response’ needed

“Governments must find evidence-based ways to boost the resilience of our societies and ... to treat those with mental ill health remotely to come out of this pandemic in good mental health,” coauthor of the paper Emily A. Holmes, PhD, of the department of psychology at Uppsala (Sweden) University, said in a press release.

“Frontline medical staff and vulnerable groups such as the elderly and those with serious mental health conditions must be prioritized for rapid mental health support,” she added.

The position paper authors call for “moment-to-moment” monitoring of anxiety, depression, self-harm, and suicide, as well as using digital technology and rapid deployment of evidence-based programs and treatments.

Patients will need to be accessible via computer, cell phone, and other remote technologies in order to receive treatment during physical isolation. However, they noted that there is no “one-size-fits-all” approach, and novel approaches custom tailored to particular populations, including frontline health care workers, are necessary.

“To make a real difference we will need to harness the tools of our digital age, finding smart new ways to measure the mental health of individuals remotely, finding creative ways to boost resilience, and finding ways to treat people in their homes. This effort must be considered central to our global response to the pandemic,” coauthor Ed Bullmore, PhD, of the department of psychiatry at the University of Cambridge (England), said in a statement.

Dr. Bullmore added that it will take “unprecedented research response if we are to limit the negative consequences of this pandemic on the mental health of our society now and in the future.”
 

Most vulnerable will bear the brunt

During a webinar held to discuss the paper, Matthew Hotopf, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London, cautioned that society’s most vulnerable citizens will bear the brunt of the pandemic’s mental health consequences.

“These individuals often have unstable housing, unstable work, and are disadvantaged in terms of their physical health and their mental health,” with a “very significant gap” in life expectancy versus the rest of the population, he said. The COVID-19 pandemic will widen the gap between “the haves and the have nots.”

“People with established and significant mental disorders are one version of the ‘have nots’ but actually it applies to a lot of people,” said Dr. Hotopf, noting that his experience of lockdown is “very different” from that of someone “living in overcrowded, unstable accommodation, with kids running around and maybe a partner who has problems with anger control.”

The authors of the position paper noted that the COVID-19 pandemic highlights several important research priorities that need to be addressed in the coming weeks and months. These include:

• Understanding the effect of COVID-19 on risk of anxiety, depression, and other outcomes, such as self-harm and suicide
• Understanding how to create physical and social supports to ensure mental health in a climate of physical distancing
• Determining the mental health consequences of social isolation for vulnerable groups, and how can these be mitigated under pandemic conditions
• Understanding the mental health impact of media reporting of COVID-19 in traditional and social media
• Determining the best methods for promoting successful adherence to behavioral advice about COVID-19 while enabling mental well-being and minimizing distress

Another area highlighted by the experts is the potential for neuropsychiatric sequelae in individuals infected with COVID-19. They called for “experimental medicine studies to validate clinical biomarkers and repurpose new treatments for the potentially neurotoxic effects of the virus.”

The authors/investigators disclosed no relevant financial relationships.

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

The COVID-19 pandemic is already affecting mental health at a population level, with increased anxiety, feelings of isolation, and concerns about access to mental health care.

Two U.K. surveys were conducted to inform research priorities for mental health research and in an effort to head off a mental health crisis. The U.K. charity MQ conducted a “stakeholder” survey of 2,198 individuals who had a lived experience of mental illness, while Ipsos MORI conducted a poll of 1,099 members of the public.

The online surveys were conducted in late March, the same week the U.K.’s nationwide lockdown measures were announced. Respondents were asked about their biggest mental health and well-being concerns and coping strategies as they relate to the COVID-19 pandemic.

Results showed that across the two surveys, respondents’ primary concern was anxiety, which was cited in 750 responses. Reported symptoms included overthinking, crying, nausea, heart palpitations, sleep disturbance, and a sense of guilt about not knowing how to help others.

In addition, respondents were worried about being social isolated, becoming mentally unwell, and having a lack of access to mental health services, as well as the impact of the pandemic on personal relationships.

The findings were used by a panel of experts to inform a position paper published in the Lancet Psychiatry. The paper outlines a proposed government response to curb the long-term “profound” and “pervasive” impact of the pandemic on mental health.
 

‘Unprecedented response’ needed

“Governments must find evidence-based ways to boost the resilience of our societies and ... to treat those with mental ill health remotely to come out of this pandemic in good mental health,” coauthor of the paper Emily A. Holmes, PhD, of the department of psychology at Uppsala (Sweden) University, said in a press release.

“Frontline medical staff and vulnerable groups such as the elderly and those with serious mental health conditions must be prioritized for rapid mental health support,” she added.

The position paper authors call for “moment-to-moment” monitoring of anxiety, depression, self-harm, and suicide, as well as using digital technology and rapid deployment of evidence-based programs and treatments.

Patients will need to be accessible via computer, cell phone, and other remote technologies in order to receive treatment during physical isolation. However, they noted that there is no “one-size-fits-all” approach, and novel approaches custom tailored to particular populations, including frontline health care workers, are necessary.

“To make a real difference we will need to harness the tools of our digital age, finding smart new ways to measure the mental health of individuals remotely, finding creative ways to boost resilience, and finding ways to treat people in their homes. This effort must be considered central to our global response to the pandemic,” coauthor Ed Bullmore, PhD, of the department of psychiatry at the University of Cambridge (England), said in a statement.

Dr. Bullmore added that it will take “unprecedented research response if we are to limit the negative consequences of this pandemic on the mental health of our society now and in the future.”
 

Most vulnerable will bear the brunt

During a webinar held to discuss the paper, Matthew Hotopf, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London, cautioned that society’s most vulnerable citizens will bear the brunt of the pandemic’s mental health consequences.

“These individuals often have unstable housing, unstable work, and are disadvantaged in terms of their physical health and their mental health,” with a “very significant gap” in life expectancy versus the rest of the population, he said. The COVID-19 pandemic will widen the gap between “the haves and the have nots.”

“People with established and significant mental disorders are one version of the ‘have nots’ but actually it applies to a lot of people,” said Dr. Hotopf, noting that his experience of lockdown is “very different” from that of someone “living in overcrowded, unstable accommodation, with kids running around and maybe a partner who has problems with anger control.”

The authors of the position paper noted that the COVID-19 pandemic highlights several important research priorities that need to be addressed in the coming weeks and months. These include:

• Understanding the effect of COVID-19 on risk of anxiety, depression, and other outcomes, such as self-harm and suicide
• Understanding how to create physical and social supports to ensure mental health in a climate of physical distancing
• Determining the mental health consequences of social isolation for vulnerable groups, and how can these be mitigated under pandemic conditions
• Understanding the mental health impact of media reporting of COVID-19 in traditional and social media
• Determining the best methods for promoting successful adherence to behavioral advice about COVID-19 while enabling mental well-being and minimizing distress

Another area highlighted by the experts is the potential for neuropsychiatric sequelae in individuals infected with COVID-19. They called for “experimental medicine studies to validate clinical biomarkers and repurpose new treatments for the potentially neurotoxic effects of the virus.”

The authors/investigators disclosed no relevant financial relationships.

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

Across the country, psychiatrists are stepping up to provide urgent care to fellow health care workers in need amid the coronavirus pandemic. They’re offering stress management strategies, spearheading unusual partnerships, and discovering that psychotherapy and medication might not be their most helpful tools to help their colleagues at this time.

“This is completely the opposite of the way we practice psychiatry,” said Allison Cotton, MD, of the University of Nevada, Reno. “Our interventions are quite different from a psychotherapeutic standpoint.”

In March, she worked with four colleagues, Suzan Song, MD, MPH, PhD; Ben Cheng, MD; Smita Gautam, MD; and Mona S. Masood, DO, to create the Physician Support Line, a confidential and free hotline that links physicians to volunteer psychiatrists who are available to listen and offer advice on coping. The hotline (888-409-0141) is available every day from 8 a.m. to midnight Eastern time. Calls typically take 15-45 minutes; no appointment is needed, and conversations are not reportable to state medical boards. At last count, Dr. Cotton said, more than 600 psychiatrists had volunteered to take shifts to talk with fellow physicians.

Courtesy Dr. Allison Cotton

“The calls can be very intense,” Dr. Cotton said, and they’re unusual for several reasons. The hotline is not like a suicide or crisis hotline, when “a person calls because they need help, and then they can go get that help – they go to the hospital and get admitted to a psychiatric unit. Our callers don’t have that luxury.”

It’s also impossible to take an extensive history and create a sophisticated, long-term treatment plan as psychiatrists would during normal office visits. At the hotline, Dr. Cotton said, “we’re really focusing on the caller’s strengths and helping them come up with a plan for today to get through whatever they’re facing,” she said.
 

Stress management is critical

Psychiatrists at the University of Colorado Anschutz Medical Campus are embracing a similar approach to help health care workers cope, said Steven Berkowitz, MD. “We focus on stress management, and the notion that they are generally healthy and understandably struggling with extraordinary circumstances,” he said. “We are conservative in our use of medications and really only prescribe medications, such as trazodone, to help with sleep. We do not use benzodiazepines unless there is a history of more severe psychiatric problems.”

The pressure on health care workers during the pandemic is intense. A survey of 1,257 workers in 34 Chinese hospitals found high levels of symptoms of depression (50%), anxiety (45%), insomnia (35%), and distress (72%). Several groups appeared to be more vulnerable: women, nurses, front-line health care workers, and those in the coronavirus-stricken city of Wuhan (JAMA Netw Open. 2020;3[3]:e203976).

In Colorado, “providers are depleted,” Dr. Berkowitz said. “We are hearing about sleep disturbances and even some traumatic nightmares from ICU staff. During our support sessions, tears come most frequently when they talk about the struggle to care for their families and how they’re putting them at risk.”

Also, he said, “one of the most upsetting issues has been around language and cultural issues. Because of the language barriers, providers cannot explain why families can’t be with their sick members, which has led to acrimony.”
 

Guilt is a prevailing theme

Guilt also is a common emotion among health care workers, said psychiatrist Tia Konzer, DO, of Charlotte, N.C. “The ones on the front line question whether they were able to do enough to save someone or if they could have done more. Those of us not on the front lines feel guilty that we’re not there with our colleagues, that we don’t face the same fears and are in the safety of our outpatient clinics.”

The focus on social distancing is creating its own strains, she said. “A lot of people are recognizing the power of human touch and how comforting that is,” she said. “The healers aren’t able to comfort the loved ones of the deceased, and we’re not able to comfort each other. And people are having a hard time not being able to hug their kids and their spouses, having to ward off their kids when they come home or avoid them until they’ve showered.”

How can mental health professionals be most helpful to health care workers in need? The simple act of listening is crucial, several such professionals said in interviews.

“Your main job is to bear witness to their experiences and to hear their story, then secondarily to make sure they have a basic self-care plan to recover from what they’re doing each day,” said psychologist Leah Welch, PhD, of the Scripps Health network in San Diego. “Don’t talk too much or try to give advice too quickly before you’ve listened to what the caregiver has shared. They’re accumulating small traumas and need time and space to sort them out, and that takes patience and a listening ear on the part of the provider. Rushing in too quickly with advice deprives them of making sense of their own experience.”

She added that “they should also be thanked for what they’re doing, because it requires skill, empathy, and courage. They are being heroic, and they need to know they’re appreciated by those of us not on the front lines for what they’re putting themselves through.”
 

Partnerships are forming

At Zuckerberg San Francisco General Hospital and Trauma Center, psychiatry chief Lisa Fortuna, MD, MPH, MDiv, said her team has had success by working closely with the hospital’s chaplains. “A lot of the staff are not saying: ‘We’re stressing out; help us.’ The chaplains had starting rounding, asking how they’re doing, and they’d open up because there was already a relationship. The chaplains are very well trained in dealing with being support for people under situations of death, loss, and immediate stress.”

The chaplains themselves became overwhelmed, and the hospital responded by reaching out to bring in more chaplains. The psychiatry team, meanwhile, worked to partner with the chaplains to provide a continuum of support for staff. “We have an opportunity to build on the trust that they have,” said Dr. Fortuna, who is an ordained Episcopal minister. “They’re the perfect partners.”

What happens now? Dr. Fortuna has seen the long-term aftermath of a crisis. She previously worked in Massachusetts and helped to support health care workers in that state after the Boston Marathon bombing.

She cautioned that health care workers may first run on adrenaline in a crisis, spurred by “heroic high energy.” But then, the full extent of the tragedy begins to set in, and they start to process their feelings. “You have to keep people going through those phases,” she said.

Going forward, she said, “there will be a prolonged tail of stress,” especially if virus outbreaks recur. “We’ll have a long time enduring this.”

Don’t forget the self-care

There was a time during the pandemic when Dr. Cotton had become so overwhelmed by anxiety that she called the Physician Support Line to get some support from fellow psychiatrists.

“I thought, ‘Why not?’” she recalled. “I helped create the hotline. Why wouldn’t I call it?”

The calls took only a few minutes but they made a difference to Dr. Cotton, who had been severely ill with what she believed was an unconfirmed case of the novel coronavirus. “I immediately felt more like I improved my outlook by focusing on what I could control,” she said, “and accepting the things I could not control.”

Many psychiatrists are finding themselves in similar situations. Fortunately, colleagues are highlighting ways for psychiatrists to care for themselves just as they care for patients.

“One of the challenges clinicians are facing is that they are living through a shared experience in this global pandemic with their patients right now,” said psychologist Randi Pochtar, PhD, who is managing support groups for front-line workers at NYU Langone Health in New York City. “Some might find the work to be overwhelming and anxiety-inducing, and others might find their work to be helpful in managing their own anxiety and stress about the pandemic and its impact.”

Dr. Cotton said her breaking points came when she felt panic amid the pandemic. “I had watched too much news, and I’d seen protesters not taking it seriously, and I was scared for my family and myself. I just needed to feel like someone heard me feeling that way.”

The calls to the hotline were helpful, she said, and so was sharing news about her illness with friends. “So many people reached out to me and checked in on me, people I haven’t seen in years, and that was immensely helpful,” she said.

This sort of personal exposure may not come naturally to physicians and nurses, she said. “We don’t seek that kind of attention when we’re ill. Instead, we say: ‘I’m fine; how are you doing?’ That’s what we do every day of our lives at work.”

How can clinicians help themselves and one another? “Clinicians in our practice have been coping and supporting each other through peer supervision, connecting with colleagues in team meetings, and simply checking in on one another,” said Dr. Pochtar. “In addition, we can adopt many of the strategies that we are likely recommending to our patients, such as maintaining routines as much as possible, engaging in regular exercise, eating well and consistently, and connecting with friends and family.”

Managers can play important roles, said Dr. Fortuna. “I’ve been checking in with my faculty, being as supportive as I can be and highlighting the extraordinary things that people are doing, like going from zero to 100 percent in setting up telehealth.”

Dr. Konzer offered another perspective on recognizing the value of the work that psychiatrists are doing. “We’re on the front line of helping heal the front line, and in that responsibility comes an additional stress,” she said. “But there’s an additional gift of being able to contribute where we are most beneficial. We can try to be present now, versus worrying about what may happen or what lies ahead, and appreciate the beauty in the helpers and the small joys of life.”

Dr. Cotton, Dr. Berkowitz, Dr. Konzer, Dr. Welch, Dr. Fortuna, and Dr. Pochtar reported no relevant disclosures.
 

Across the country, psychiatrists are stepping up to provide urgent care to fellow health care workers in need amid the coronavirus pandemic. They’re offering stress management strategies, spearheading unusual partnerships, and discovering that psychotherapy and medication might not be their most helpful tools to help their colleagues at this time.

“This is completely the opposite of the way we practice psychiatry,” said Allison Cotton, MD, of the University of Nevada, Reno. “Our interventions are quite different from a psychotherapeutic standpoint.”

In March, she worked with four colleagues, Suzan Song, MD, MPH, PhD; Ben Cheng, MD; Smita Gautam, MD; and Mona S. Masood, DO, to create the Physician Support Line, a confidential and free hotline that links physicians to volunteer psychiatrists who are available to listen and offer advice on coping. The hotline (888-409-0141) is available every day from 8 a.m. to midnight Eastern time. Calls typically take 15-45 minutes; no appointment is needed, and conversations are not reportable to state medical boards. At last count, Dr. Cotton said, more than 600 psychiatrists had volunteered to take shifts to talk with fellow physicians.

Courtesy Dr. Allison Cotton

“The calls can be very intense,” Dr. Cotton said, and they’re unusual for several reasons. The hotline is not like a suicide or crisis hotline, when “a person calls because they need help, and then they can go get that help – they go to the hospital and get admitted to a psychiatric unit. Our callers don’t have that luxury.”

It’s also impossible to take an extensive history and create a sophisticated, long-term treatment plan as psychiatrists would during normal office visits. At the hotline, Dr. Cotton said, “we’re really focusing on the caller’s strengths and helping them come up with a plan for today to get through whatever they’re facing,” she said.
 

Stress management is critical

Psychiatrists at the University of Colorado Anschutz Medical Campus are embracing a similar approach to help health care workers cope, said Steven Berkowitz, MD. “We focus on stress management, and the notion that they are generally healthy and understandably struggling with extraordinary circumstances,” he said. “We are conservative in our use of medications and really only prescribe medications, such as trazodone, to help with sleep. We do not use benzodiazepines unless there is a history of more severe psychiatric problems.”

The pressure on health care workers during the pandemic is intense. A survey of 1,257 workers in 34 Chinese hospitals found high levels of symptoms of depression (50%), anxiety (45%), insomnia (35%), and distress (72%). Several groups appeared to be more vulnerable: women, nurses, front-line health care workers, and those in the coronavirus-stricken city of Wuhan (JAMA Netw Open. 2020;3[3]:e203976).

In Colorado, “providers are depleted,” Dr. Berkowitz said. “We are hearing about sleep disturbances and even some traumatic nightmares from ICU staff. During our support sessions, tears come most frequently when they talk about the struggle to care for their families and how they’re putting them at risk.”

Also, he said, “one of the most upsetting issues has been around language and cultural issues. Because of the language barriers, providers cannot explain why families can’t be with their sick members, which has led to acrimony.”
 

Guilt is a prevailing theme

Guilt also is a common emotion among health care workers, said psychiatrist Tia Konzer, DO, of Charlotte, N.C. “The ones on the front line question whether they were able to do enough to save someone or if they could have done more. Those of us not on the front lines feel guilty that we’re not there with our colleagues, that we don’t face the same fears and are in the safety of our outpatient clinics.”

The focus on social distancing is creating its own strains, she said. “A lot of people are recognizing the power of human touch and how comforting that is,” she said. “The healers aren’t able to comfort the loved ones of the deceased, and we’re not able to comfort each other. And people are having a hard time not being able to hug their kids and their spouses, having to ward off their kids when they come home or avoid them until they’ve showered.”

How can mental health professionals be most helpful to health care workers in need? The simple act of listening is crucial, several such professionals said in interviews.

“Your main job is to bear witness to their experiences and to hear their story, then secondarily to make sure they have a basic self-care plan to recover from what they’re doing each day,” said psychologist Leah Welch, PhD, of the Scripps Health network in San Diego. “Don’t talk too much or try to give advice too quickly before you’ve listened to what the caregiver has shared. They’re accumulating small traumas and need time and space to sort them out, and that takes patience and a listening ear on the part of the provider. Rushing in too quickly with advice deprives them of making sense of their own experience.”

She added that “they should also be thanked for what they’re doing, because it requires skill, empathy, and courage. They are being heroic, and they need to know they’re appreciated by those of us not on the front lines for what they’re putting themselves through.”
 

Partnerships are forming

At Zuckerberg San Francisco General Hospital and Trauma Center, psychiatry chief Lisa Fortuna, MD, MPH, MDiv, said her team has had success by working closely with the hospital’s chaplains. “A lot of the staff are not saying: ‘We’re stressing out; help us.’ The chaplains had starting rounding, asking how they’re doing, and they’d open up because there was already a relationship. The chaplains are very well trained in dealing with being support for people under situations of death, loss, and immediate stress.”

The chaplains themselves became overwhelmed, and the hospital responded by reaching out to bring in more chaplains. The psychiatry team, meanwhile, worked to partner with the chaplains to provide a continuum of support for staff. “We have an opportunity to build on the trust that they have,” said Dr. Fortuna, who is an ordained Episcopal minister. “They’re the perfect partners.”

What happens now? Dr. Fortuna has seen the long-term aftermath of a crisis. She previously worked in Massachusetts and helped to support health care workers in that state after the Boston Marathon bombing.

She cautioned that health care workers may first run on adrenaline in a crisis, spurred by “heroic high energy.” But then, the full extent of the tragedy begins to set in, and they start to process their feelings. “You have to keep people going through those phases,” she said.

Going forward, she said, “there will be a prolonged tail of stress,” especially if virus outbreaks recur. “We’ll have a long time enduring this.”

Don’t forget the self-care

There was a time during the pandemic when Dr. Cotton had become so overwhelmed by anxiety that she called the Physician Support Line to get some support from fellow psychiatrists.

“I thought, ‘Why not?’” she recalled. “I helped create the hotline. Why wouldn’t I call it?”

The calls took only a few minutes but they made a difference to Dr. Cotton, who had been severely ill with what she believed was an unconfirmed case of the novel coronavirus. “I immediately felt more like I improved my outlook by focusing on what I could control,” she said, “and accepting the things I could not control.”

Many psychiatrists are finding themselves in similar situations. Fortunately, colleagues are highlighting ways for psychiatrists to care for themselves just as they care for patients.

“One of the challenges clinicians are facing is that they are living through a shared experience in this global pandemic with their patients right now,” said psychologist Randi Pochtar, PhD, who is managing support groups for front-line workers at NYU Langone Health in New York City. “Some might find the work to be overwhelming and anxiety-inducing, and others might find their work to be helpful in managing their own anxiety and stress about the pandemic and its impact.”

Dr. Cotton said her breaking points came when she felt panic amid the pandemic. “I had watched too much news, and I’d seen protesters not taking it seriously, and I was scared for my family and myself. I just needed to feel like someone heard me feeling that way.”

The calls to the hotline were helpful, she said, and so was sharing news about her illness with friends. “So many people reached out to me and checked in on me, people I haven’t seen in years, and that was immensely helpful,” she said.

This sort of personal exposure may not come naturally to physicians and nurses, she said. “We don’t seek that kind of attention when we’re ill. Instead, we say: ‘I’m fine; how are you doing?’ That’s what we do every day of our lives at work.”

How can clinicians help themselves and one another? “Clinicians in our practice have been coping and supporting each other through peer supervision, connecting with colleagues in team meetings, and simply checking in on one another,” said Dr. Pochtar. “In addition, we can adopt many of the strategies that we are likely recommending to our patients, such as maintaining routines as much as possible, engaging in regular exercise, eating well and consistently, and connecting with friends and family.”

Managers can play important roles, said Dr. Fortuna. “I’ve been checking in with my faculty, being as supportive as I can be and highlighting the extraordinary things that people are doing, like going from zero to 100 percent in setting up telehealth.”

Dr. Konzer offered another perspective on recognizing the value of the work that psychiatrists are doing. “We’re on the front line of helping heal the front line, and in that responsibility comes an additional stress,” she said. “But there’s an additional gift of being able to contribute where we are most beneficial. We can try to be present now, versus worrying about what may happen or what lies ahead, and appreciate the beauty in the helpers and the small joys of life.”

Dr. Cotton, Dr. Berkowitz, Dr. Konzer, Dr. Welch, Dr. Fortuna, and Dr. Pochtar reported no relevant disclosures.
 

Across the country, psychiatrists are stepping up to provide urgent care to fellow health care workers in need amid the coronavirus pandemic. They’re offering stress management strategies, spearheading unusual partnerships, and discovering that psychotherapy and medication might not be their most helpful tools to help their colleagues at this time.

“This is completely the opposite of the way we practice psychiatry,” said Allison Cotton, MD, of the University of Nevada, Reno. “Our interventions are quite different from a psychotherapeutic standpoint.”

In March, she worked with four colleagues, Suzan Song, MD, MPH, PhD; Ben Cheng, MD; Smita Gautam, MD; and Mona S. Masood, DO, to create the Physician Support Line, a confidential and free hotline that links physicians to volunteer psychiatrists who are available to listen and offer advice on coping. The hotline (888-409-0141) is available every day from 8 a.m. to midnight Eastern time. Calls typically take 15-45 minutes; no appointment is needed, and conversations are not reportable to state medical boards. At last count, Dr. Cotton said, more than 600 psychiatrists had volunteered to take shifts to talk with fellow physicians.

Courtesy Dr. Allison Cotton

“The calls can be very intense,” Dr. Cotton said, and they’re unusual for several reasons. The hotline is not like a suicide or crisis hotline, when “a person calls because they need help, and then they can go get that help – they go to the hospital and get admitted to a psychiatric unit. Our callers don’t have that luxury.”

It’s also impossible to take an extensive history and create a sophisticated, long-term treatment plan as psychiatrists would during normal office visits. At the hotline, Dr. Cotton said, “we’re really focusing on the caller’s strengths and helping them come up with a plan for today to get through whatever they’re facing,” she said.
 

Stress management is critical

Psychiatrists at the University of Colorado Anschutz Medical Campus are embracing a similar approach to help health care workers cope, said Steven Berkowitz, MD. “We focus on stress management, and the notion that they are generally healthy and understandably struggling with extraordinary circumstances,” he said. “We are conservative in our use of medications and really only prescribe medications, such as trazodone, to help with sleep. We do not use benzodiazepines unless there is a history of more severe psychiatric problems.”

The pressure on health care workers during the pandemic is intense. A survey of 1,257 workers in 34 Chinese hospitals found high levels of symptoms of depression (50%), anxiety (45%), insomnia (35%), and distress (72%). Several groups appeared to be more vulnerable: women, nurses, front-line health care workers, and those in the coronavirus-stricken city of Wuhan (JAMA Netw Open. 2020;3[3]:e203976).

In Colorado, “providers are depleted,” Dr. Berkowitz said. “We are hearing about sleep disturbances and even some traumatic nightmares from ICU staff. During our support sessions, tears come most frequently when they talk about the struggle to care for their families and how they’re putting them at risk.”

Also, he said, “one of the most upsetting issues has been around language and cultural issues. Because of the language barriers, providers cannot explain why families can’t be with their sick members, which has led to acrimony.”
 

Guilt is a prevailing theme

Guilt also is a common emotion among health care workers, said psychiatrist Tia Konzer, DO, of Charlotte, N.C. “The ones on the front line question whether they were able to do enough to save someone or if they could have done more. Those of us not on the front lines feel guilty that we’re not there with our colleagues, that we don’t face the same fears and are in the safety of our outpatient clinics.”

The focus on social distancing is creating its own strains, she said. “A lot of people are recognizing the power of human touch and how comforting that is,” she said. “The healers aren’t able to comfort the loved ones of the deceased, and we’re not able to comfort each other. And people are having a hard time not being able to hug their kids and their spouses, having to ward off their kids when they come home or avoid them until they’ve showered.”

How can mental health professionals be most helpful to health care workers in need? The simple act of listening is crucial, several such professionals said in interviews.

“Your main job is to bear witness to their experiences and to hear their story, then secondarily to make sure they have a basic self-care plan to recover from what they’re doing each day,” said psychologist Leah Welch, PhD, of the Scripps Health network in San Diego. “Don’t talk too much or try to give advice too quickly before you’ve listened to what the caregiver has shared. They’re accumulating small traumas and need time and space to sort them out, and that takes patience and a listening ear on the part of the provider. Rushing in too quickly with advice deprives them of making sense of their own experience.”

She added that “they should also be thanked for what they’re doing, because it requires skill, empathy, and courage. They are being heroic, and they need to know they’re appreciated by those of us not on the front lines for what they’re putting themselves through.”
 

Partnerships are forming

At Zuckerberg San Francisco General Hospital and Trauma Center, psychiatry chief Lisa Fortuna, MD, MPH, MDiv, said her team has had success by working closely with the hospital’s chaplains. “A lot of the staff are not saying: ‘We’re stressing out; help us.’ The chaplains had starting rounding, asking how they’re doing, and they’d open up because there was already a relationship. The chaplains are very well trained in dealing with being support for people under situations of death, loss, and immediate stress.”

The chaplains themselves became overwhelmed, and the hospital responded by reaching out to bring in more chaplains. The psychiatry team, meanwhile, worked to partner with the chaplains to provide a continuum of support for staff. “We have an opportunity to build on the trust that they have,” said Dr. Fortuna, who is an ordained Episcopal minister. “They’re the perfect partners.”

What happens now? Dr. Fortuna has seen the long-term aftermath of a crisis. She previously worked in Massachusetts and helped to support health care workers in that state after the Boston Marathon bombing.

She cautioned that health care workers may first run on adrenaline in a crisis, spurred by “heroic high energy.” But then, the full extent of the tragedy begins to set in, and they start to process their feelings. “You have to keep people going through those phases,” she said.

Going forward, she said, “there will be a prolonged tail of stress,” especially if virus outbreaks recur. “We’ll have a long time enduring this.”

Don’t forget the self-care

There was a time during the pandemic when Dr. Cotton had become so overwhelmed by anxiety that she called the Physician Support Line to get some support from fellow psychiatrists.

“I thought, ‘Why not?’” she recalled. “I helped create the hotline. Why wouldn’t I call it?”

The calls took only a few minutes but they made a difference to Dr. Cotton, who had been severely ill with what she believed was an unconfirmed case of the novel coronavirus. “I immediately felt more like I improved my outlook by focusing on what I could control,” she said, “and accepting the things I could not control.”

Many psychiatrists are finding themselves in similar situations. Fortunately, colleagues are highlighting ways for psychiatrists to care for themselves just as they care for patients.

“One of the challenges clinicians are facing is that they are living through a shared experience in this global pandemic with their patients right now,” said psychologist Randi Pochtar, PhD, who is managing support groups for front-line workers at NYU Langone Health in New York City. “Some might find the work to be overwhelming and anxiety-inducing, and others might find their work to be helpful in managing their own anxiety and stress about the pandemic and its impact.”

Dr. Cotton said her breaking points came when she felt panic amid the pandemic. “I had watched too much news, and I’d seen protesters not taking it seriously, and I was scared for my family and myself. I just needed to feel like someone heard me feeling that way.”

The calls to the hotline were helpful, she said, and so was sharing news about her illness with friends. “So many people reached out to me and checked in on me, people I haven’t seen in years, and that was immensely helpful,” she said.

This sort of personal exposure may not come naturally to physicians and nurses, she said. “We don’t seek that kind of attention when we’re ill. Instead, we say: ‘I’m fine; how are you doing?’ That’s what we do every day of our lives at work.”

How can clinicians help themselves and one another? “Clinicians in our practice have been coping and supporting each other through peer supervision, connecting with colleagues in team meetings, and simply checking in on one another,” said Dr. Pochtar. “In addition, we can adopt many of the strategies that we are likely recommending to our patients, such as maintaining routines as much as possible, engaging in regular exercise, eating well and consistently, and connecting with friends and family.”

Managers can play important roles, said Dr. Fortuna. “I’ve been checking in with my faculty, being as supportive as I can be and highlighting the extraordinary things that people are doing, like going from zero to 100 percent in setting up telehealth.”

Dr. Konzer offered another perspective on recognizing the value of the work that psychiatrists are doing. “We’re on the front line of helping heal the front line, and in that responsibility comes an additional stress,” she said. “But there’s an additional gift of being able to contribute where we are most beneficial. We can try to be present now, versus worrying about what may happen or what lies ahead, and appreciate the beauty in the helpers and the small joys of life.”

Dr. Cotton, Dr. Berkowitz, Dr. Konzer, Dr. Welch, Dr. Fortuna, and Dr. Pochtar reported no relevant disclosures.
 

Hospitalized COVID-19 patients with hypertension and on treatment with an renin-angiotensin system inhibiting drug had significantly better survival, compared with similar hypertensive patients not on these drugs, in observational, propensity score–matched analyses that drew from a pool of more than 3,430 patients hospitalized at any of nine Chinese hospitals during December 2019–February 2020.

Courtesy CDC

“Among patients with hypertension hospitalized with COVID-19, inpatient treatment with ACEI [ACE inhibitor]/ARB [angiotensin receptor blocker] was associated with lower risk of all-cause mortality, compared with ACEI/ARB nonusers, during 28 days of follow-up. While study interpretation needs to consider the potential for residual confounders, it is unlikely that inpatient ACEI/ARB would be associated with an increased risk of mortality,” wrote Peng Zhang, MD, a cardiology researcher at Renmin Hospital of Wuhan University, China, and coauthors in Circulations Research, buttressing recent recommendations from several medical societies to maintain COVID-19 patients on these drugs.

“Our findings in this paper provide evidence supporting continuous use of ACEI/ARB for patients with hypertension infected with SARS-COV-2,” wrote the authors, backing up recent recommendations from cardiology societies that called for not stopping ACEI/ARB prescriptions in patients at risk for contracting or already have COVID-19 infection, including a statement from the American College of Cardiology, American Heart Association, and Heart Failure Society of America, and also guidance from the European Society of Cardiology.

The study included 1,128 patients with a history of hypertension, including 188 (17%) who received an ACEI/ARB drug during hospitalization. During 28-day follow-up, 99 died (9%), including 7 deaths among the 188 patients (4%) on an ACEI/ARB drug and 92 deaths among the 940 other hypertensive patients (10%).

The authors ran several analyses to try to adjust for the influence of possible confounders. A mixed-effect Cox model with four adjusted variables showed that treatment with an ACEI/ARB drug was tied to a statistically significant 58% lower death rate, compared with patients not receiving these drugs.

The researchers also ran several propensity score–adjusted analyses. One matched 174 of the patients who received an ACEI/ARB drug with 522 who did not, and comparing these two matched arms showed that ACEI/ARB use was linked with a statistically significant 63% cut in mortality, compared with patients not getting these drugs. A second propensity score–matched analysis first excluded the 383 patients who were hypertensive but received no antihypertensive medication during hospitalization. From the remaining 745 patients who received at least one antihypertensive medication, the authors identified 181 patients who received an ACEI/ARB and propensity-score matched them with 181 hypertensive patients on a different medication class, finding that ACEI/ARB use linked with a statistically significant 71% lower rate of all-cause mortality.

Additional analyses also showed that patients with hypertension had a statistically significant, 41% increased rate of all-cause death, compared with patients without hypertension, and another propensity score–matched analysis showed that among hypertensives treatment with an ACEI/ARB drug was linked with a statistically significant 68% reduced rate of septic shock.

Although this report was received with caution and some skepticism, it was also acknowledged as a step forward in the creation of an evidence base addressing ACEI/ARB treatment during COVID-19 infection.

“These drugs are lifesaving and should not be discontinued” for patients with hypertension, heart failure, and other cardiovascular disease, commented Gian Paolo Rossi, MD, professor and chair of medicine and director of the high blood pressure unit at the University of Padua (Italy). The analysis by Zhang and associates included the largest number of hospitalized COVID-19 patients with hypertension yet reported to assess the impact of treatment with ACEI/ARB drugs, and adds important evidence in favor of continuing these drugs in patients who develop COVID-19 infection, Dr. Rossi said in an interview. He recently coauthored a review that argued against ACEI/ARB discontinuation in COVID-19 patients based on previously reported evidence (Elife. 2020 Apr 6. doi: 10.7554/eLife.57278).

But other researchers take a wary view of the potential impact of ACEI/ARB agents. “If ACEI/ARB therapy increases ACE2 and the virus down-regulates it, and because ACE2 is the viral entry port into cells, why would ACE2-mediated down-regulation of the renin-angiotensin-aldosterone system lead to amelioration of [COVID-19] disease?” asked Laurence W. Busse, MD, a critical care physician at Emory University, Atlanta. “A number of issues could potentially confound the results, including the definition of COVID-19 and imbalance of antiviral therapy,” added Dr. Busse, who recently coauthored an editorial that posited using angiotensin II (Giapreza), an approved vasopressor drug, as an alternative renin-angiotensin system intervention for COVID-19 patients including both those in shock as well as potentially those not in shock (Crit Care. 2020 Apr 7. doi: 10.1186/s13054-020-02862-1). Despite these caveats, the new Chinese findings reported by Dr. Zhang and associates “are hypothesis generating and worth further exploration.”

The authors of an editorial that accompanied the Zhang study in Circulation Research made similar points. “While the investigators used standard techniques to attempt to reduce bias in this observational study via propensity matching, it is not a randomized study and the residual confounding inherent to this approach renders the conclusions hypothesis generating at best,” wrote Ravi V. Shah, MD, and two coauthors in the editorial (Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317174). They also agreed with the several society statements that have supported continued use of ACEI/ARB drugs in COVID-19 patients. “Withdrawal of these medications in the context of those conditions in which they have proven benefit (e.g., heart failure with reduced left ventricular ejection fraction) may actually inflict more harm than good,” they warned. “In the end we must rely on randomized clinical science,” and while this level of evidence is currently lacking, “the study by Zhang and colleagues is a direct step toward that goal.”

Dr. Zhang and coauthors had no commercial disclosures. Dr. Rossi and Dr. Busse had no disclosures. The authors of the Circulation Research editorial reported several disclosures.

mzoler@mdedge.com

SOURCE: Zhang P et al. Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317134.

Hospitalized COVID-19 patients with hypertension and on treatment with an renin-angiotensin system inhibiting drug had significantly better survival, compared with similar hypertensive patients not on these drugs, in observational, propensity score–matched analyses that drew from a pool of more than 3,430 patients hospitalized at any of nine Chinese hospitals during December 2019–February 2020.

Courtesy CDC

“Among patients with hypertension hospitalized with COVID-19, inpatient treatment with ACEI [ACE inhibitor]/ARB [angiotensin receptor blocker] was associated with lower risk of all-cause mortality, compared with ACEI/ARB nonusers, during 28 days of follow-up. While study interpretation needs to consider the potential for residual confounders, it is unlikely that inpatient ACEI/ARB would be associated with an increased risk of mortality,” wrote Peng Zhang, MD, a cardiology researcher at Renmin Hospital of Wuhan University, China, and coauthors in Circulations Research, buttressing recent recommendations from several medical societies to maintain COVID-19 patients on these drugs.

“Our findings in this paper provide evidence supporting continuous use of ACEI/ARB for patients with hypertension infected with SARS-COV-2,” wrote the authors, backing up recent recommendations from cardiology societies that called for not stopping ACEI/ARB prescriptions in patients at risk for contracting or already have COVID-19 infection, including a statement from the American College of Cardiology, American Heart Association, and Heart Failure Society of America, and also guidance from the European Society of Cardiology.

The study included 1,128 patients with a history of hypertension, including 188 (17%) who received an ACEI/ARB drug during hospitalization. During 28-day follow-up, 99 died (9%), including 7 deaths among the 188 patients (4%) on an ACEI/ARB drug and 92 deaths among the 940 other hypertensive patients (10%).

The authors ran several analyses to try to adjust for the influence of possible confounders. A mixed-effect Cox model with four adjusted variables showed that treatment with an ACEI/ARB drug was tied to a statistically significant 58% lower death rate, compared with patients not receiving these drugs.

The researchers also ran several propensity score–adjusted analyses. One matched 174 of the patients who received an ACEI/ARB drug with 522 who did not, and comparing these two matched arms showed that ACEI/ARB use was linked with a statistically significant 63% cut in mortality, compared with patients not getting these drugs. A second propensity score–matched analysis first excluded the 383 patients who were hypertensive but received no antihypertensive medication during hospitalization. From the remaining 745 patients who received at least one antihypertensive medication, the authors identified 181 patients who received an ACEI/ARB and propensity-score matched them with 181 hypertensive patients on a different medication class, finding that ACEI/ARB use linked with a statistically significant 71% lower rate of all-cause mortality.

Additional analyses also showed that patients with hypertension had a statistically significant, 41% increased rate of all-cause death, compared with patients without hypertension, and another propensity score–matched analysis showed that among hypertensives treatment with an ACEI/ARB drug was linked with a statistically significant 68% reduced rate of septic shock.

Although this report was received with caution and some skepticism, it was also acknowledged as a step forward in the creation of an evidence base addressing ACEI/ARB treatment during COVID-19 infection.

“These drugs are lifesaving and should not be discontinued” for patients with hypertension, heart failure, and other cardiovascular disease, commented Gian Paolo Rossi, MD, professor and chair of medicine and director of the high blood pressure unit at the University of Padua (Italy). The analysis by Zhang and associates included the largest number of hospitalized COVID-19 patients with hypertension yet reported to assess the impact of treatment with ACEI/ARB drugs, and adds important evidence in favor of continuing these drugs in patients who develop COVID-19 infection, Dr. Rossi said in an interview. He recently coauthored a review that argued against ACEI/ARB discontinuation in COVID-19 patients based on previously reported evidence (Elife. 2020 Apr 6. doi: 10.7554/eLife.57278).

But other researchers take a wary view of the potential impact of ACEI/ARB agents. “If ACEI/ARB therapy increases ACE2 and the virus down-regulates it, and because ACE2 is the viral entry port into cells, why would ACE2-mediated down-regulation of the renin-angiotensin-aldosterone system lead to amelioration of [COVID-19] disease?” asked Laurence W. Busse, MD, a critical care physician at Emory University, Atlanta. “A number of issues could potentially confound the results, including the definition of COVID-19 and imbalance of antiviral therapy,” added Dr. Busse, who recently coauthored an editorial that posited using angiotensin II (Giapreza), an approved vasopressor drug, as an alternative renin-angiotensin system intervention for COVID-19 patients including both those in shock as well as potentially those not in shock (Crit Care. 2020 Apr 7. doi: 10.1186/s13054-020-02862-1). Despite these caveats, the new Chinese findings reported by Dr. Zhang and associates “are hypothesis generating and worth further exploration.”

The authors of an editorial that accompanied the Zhang study in Circulation Research made similar points. “While the investigators used standard techniques to attempt to reduce bias in this observational study via propensity matching, it is not a randomized study and the residual confounding inherent to this approach renders the conclusions hypothesis generating at best,” wrote Ravi V. Shah, MD, and two coauthors in the editorial (Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317174). They also agreed with the several society statements that have supported continued use of ACEI/ARB drugs in COVID-19 patients. “Withdrawal of these medications in the context of those conditions in which they have proven benefit (e.g., heart failure with reduced left ventricular ejection fraction) may actually inflict more harm than good,” they warned. “In the end we must rely on randomized clinical science,” and while this level of evidence is currently lacking, “the study by Zhang and colleagues is a direct step toward that goal.”

Dr. Zhang and coauthors had no commercial disclosures. Dr. Rossi and Dr. Busse had no disclosures. The authors of the Circulation Research editorial reported several disclosures.

mzoler@mdedge.com

SOURCE: Zhang P et al. Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317134.

Hospitalized COVID-19 patients with hypertension and on treatment with an renin-angiotensin system inhibiting drug had significantly better survival, compared with similar hypertensive patients not on these drugs, in observational, propensity score–matched analyses that drew from a pool of more than 3,430 patients hospitalized at any of nine Chinese hospitals during December 2019–February 2020.

Courtesy CDC

“Among patients with hypertension hospitalized with COVID-19, inpatient treatment with ACEI [ACE inhibitor]/ARB [angiotensin receptor blocker] was associated with lower risk of all-cause mortality, compared with ACEI/ARB nonusers, during 28 days of follow-up. While study interpretation needs to consider the potential for residual confounders, it is unlikely that inpatient ACEI/ARB would be associated with an increased risk of mortality,” wrote Peng Zhang, MD, a cardiology researcher at Renmin Hospital of Wuhan University, China, and coauthors in Circulations Research, buttressing recent recommendations from several medical societies to maintain COVID-19 patients on these drugs.

“Our findings in this paper provide evidence supporting continuous use of ACEI/ARB for patients with hypertension infected with SARS-COV-2,” wrote the authors, backing up recent recommendations from cardiology societies that called for not stopping ACEI/ARB prescriptions in patients at risk for contracting or already have COVID-19 infection, including a statement from the American College of Cardiology, American Heart Association, and Heart Failure Society of America, and also guidance from the European Society of Cardiology.

The study included 1,128 patients with a history of hypertension, including 188 (17%) who received an ACEI/ARB drug during hospitalization. During 28-day follow-up, 99 died (9%), including 7 deaths among the 188 patients (4%) on an ACEI/ARB drug and 92 deaths among the 940 other hypertensive patients (10%).

The authors ran several analyses to try to adjust for the influence of possible confounders. A mixed-effect Cox model with four adjusted variables showed that treatment with an ACEI/ARB drug was tied to a statistically significant 58% lower death rate, compared with patients not receiving these drugs.

The researchers also ran several propensity score–adjusted analyses. One matched 174 of the patients who received an ACEI/ARB drug with 522 who did not, and comparing these two matched arms showed that ACEI/ARB use was linked with a statistically significant 63% cut in mortality, compared with patients not getting these drugs. A second propensity score–matched analysis first excluded the 383 patients who were hypertensive but received no antihypertensive medication during hospitalization. From the remaining 745 patients who received at least one antihypertensive medication, the authors identified 181 patients who received an ACEI/ARB and propensity-score matched them with 181 hypertensive patients on a different medication class, finding that ACEI/ARB use linked with a statistically significant 71% lower rate of all-cause mortality.

Additional analyses also showed that patients with hypertension had a statistically significant, 41% increased rate of all-cause death, compared with patients without hypertension, and another propensity score–matched analysis showed that among hypertensives treatment with an ACEI/ARB drug was linked with a statistically significant 68% reduced rate of septic shock.

Although this report was received with caution and some skepticism, it was also acknowledged as a step forward in the creation of an evidence base addressing ACEI/ARB treatment during COVID-19 infection.

“These drugs are lifesaving and should not be discontinued” for patients with hypertension, heart failure, and other cardiovascular disease, commented Gian Paolo Rossi, MD, professor and chair of medicine and director of the high blood pressure unit at the University of Padua (Italy). The analysis by Zhang and associates included the largest number of hospitalized COVID-19 patients with hypertension yet reported to assess the impact of treatment with ACEI/ARB drugs, and adds important evidence in favor of continuing these drugs in patients who develop COVID-19 infection, Dr. Rossi said in an interview. He recently coauthored a review that argued against ACEI/ARB discontinuation in COVID-19 patients based on previously reported evidence (Elife. 2020 Apr 6. doi: 10.7554/eLife.57278).

But other researchers take a wary view of the potential impact of ACEI/ARB agents. “If ACEI/ARB therapy increases ACE2 and the virus down-regulates it, and because ACE2 is the viral entry port into cells, why would ACE2-mediated down-regulation of the renin-angiotensin-aldosterone system lead to amelioration of [COVID-19] disease?” asked Laurence W. Busse, MD, a critical care physician at Emory University, Atlanta. “A number of issues could potentially confound the results, including the definition of COVID-19 and imbalance of antiviral therapy,” added Dr. Busse, who recently coauthored an editorial that posited using angiotensin II (Giapreza), an approved vasopressor drug, as an alternative renin-angiotensin system intervention for COVID-19 patients including both those in shock as well as potentially those not in shock (Crit Care. 2020 Apr 7. doi: 10.1186/s13054-020-02862-1). Despite these caveats, the new Chinese findings reported by Dr. Zhang and associates “are hypothesis generating and worth further exploration.”

The authors of an editorial that accompanied the Zhang study in Circulation Research made similar points. “While the investigators used standard techniques to attempt to reduce bias in this observational study via propensity matching, it is not a randomized study and the residual confounding inherent to this approach renders the conclusions hypothesis generating at best,” wrote Ravi V. Shah, MD, and two coauthors in the editorial (Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317174). They also agreed with the several society statements that have supported continued use of ACEI/ARB drugs in COVID-19 patients. “Withdrawal of these medications in the context of those conditions in which they have proven benefit (e.g., heart failure with reduced left ventricular ejection fraction) may actually inflict more harm than good,” they warned. “In the end we must rely on randomized clinical science,” and while this level of evidence is currently lacking, “the study by Zhang and colleagues is a direct step toward that goal.”

Dr. Zhang and coauthors had no commercial disclosures. Dr. Rossi and Dr. Busse had no disclosures. The authors of the Circulation Research editorial reported several disclosures.

mzoler@mdedge.com

SOURCE: Zhang P et al. Circ Res. 2020 Apr 17. doi: 10.1161/CIRCRESAHA.120.317134.

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

sworcester@mdedge.com

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

sworcester@mdedge.com

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

sworcester@mdedge.com

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

Evidence on the link between smoking and the likelihood of developing COVID-19 remains unclear to date, but quitting smoking is likely to lower the risk of developing more severe or fatal cases of the infection, according to research from several recent papers.

bilderbox/fotolia.com

Interest in how tobacco use affects COVID-19 infection rates stems from research showing that men at the epicenter of the outbreak in China having a higher early mortality rate. Early reports from China showed a case fatality rate of 4.7% for men, compared with 2.8% for women, according to the World Health Organization. The virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2, is suspected to enter a cell using the ACE2 receptor. Since smoking up-regulates this receptor, one popular theory is that smoking can increase the risk of COVID-19 or exacerbate symptoms of an existing infection (Eur Respir J. 2020 Apr 8. doi: 10.1183/13993003.00688-2020). In China, about half of men are active smokers, compared with 2.7% of women (Transl Lung Cancer Res. 2019;8[Suppl 1]:S21-30), so this association would explain the severe cases and increased mortality in this group. In response to potential risk for public health, the World Health Organization, Centers for Disease Control and Prevention, the Attorney General of Massachusetts, and other organizations have warned that smoking may increase one’s risk of transmitting and developing COVID-19 or may worsen the infection.

“While it is easy to jump to the conclusion that more ACE2 means more susceptibility to severe infection, there is no evidence to support this,” Brandon Michael Henry, MD, of the cardiac intensive care unit and the Heart Institute at Cincinnati Children’s Hospital Medical Center, said in an interview. “Moreover, some would argue (including myself) that increased ACE2 may in fact be protective, as ACE2 decreases the levels of angiotensin-2 which likely plays a significant role in the pathophysiology of ARDS.”

Some researchers have examined the limited evidence of smoking on COVID-19 risk and come to preliminary conclusions. In a letter to the editor recently published in the European Journal of Internal Medicine, Dr. Henry and Giuseppe Lippi, MD, of the section of clinical biochemistry in the department of neuroscience, biomedicine, and movement at the University of Verona (Italy), performed a meta-analysis of papers examining smoking and COVID-19 up to March 9, 2020 and identified five articles with 1,399 COVID-19 cases (Eur J Intern Med. 2020 Mar 16. doi: 10.1016/j.ejim.2020.03.014).

“Given the fact that COVID-19 is a primarily respiratory illness, smoking was one of first risk factors we examined,” Dr. Henry said.

They noted that a study by Liu et al. in the Chinese Medical Journal was the only paper that showed a significant association between smoking status and COVID-19 case severity (Chin Med J [Engl]. 2020 Feb 28. doi: 10.1097/CM9.0000000000000775), while the four other studies showed no significant association. The pooled data of all five studies showed an association that was not statistically significant (odds ratio, 1.69; 95% confidence interval, 0.41-6.92; P = .254). When Dr. Lippi and Dr. Henry performed the analysis again after removing a paper by Guan et al. (N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032) comprising 89.5% of patients in the pooled analysis, there was no significant association (OR, 4.35; 95% CI, 0.86-21.86; P = .129).

Constantine I. Vardavas, MD, FCCP, of the department of oral health policy and epidemiology at Harvard School of Dental Medicine, Boston, and Katerina Nikitara, of the University of Crete in Heraklion, Greece, also published a systematic review in Tobacco Induced Diseases of five studies evaluating smoking and COVID-19 (Tob Induc Dis. 2020. doi: 10.18332/tid/119324). Of the studies chosen for the review, four were shared with the paper by Dr. Lippi and Dr. Henry. They found “a higher percentage of smokers” made up severe COVID-19 cases, but acknowledged the majority of these were from the largest study by Guan et al. Overall, they calculated smokers carried a risk ratio of 1.4 (95% CI, 0.98-2.00) for developing severe COVID-19 symptoms, and were over twice as likely to be admitted to an ICU, require a mechanical ventilator, or die from COVID-19, compared with patients who did not smoke (RR, 2.4; 95% CI, 1.43-4.04).

“Although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19,” Dr. Vardavas and Ms. Nikitara concluded.

However, the association between smoking and severe disease was not significant, and it is not immediately clear how the analysis was performed based on the details in the editorial. “Both of our reports were limited by a lack of data adjusted for age, sex, and comorbidities which may influence any analysis on smoking,” Dr. Henry said.

Some researchers have proposed collecting information on smoking status and conducting further research on whether vaping devices like e-cigarettes also impact COVID-19 cases. An editorial by Samuel Brake and colleagues published in the Journal of Clinical Medicine proposed the ACE2-receptor binding site as an area of interest for COVID-19 and as a potential therapeutic target (J Clin Med. 2020 Mar 20. doi: 10.3390/jcm9030841).

Ultimately, whether smoking itself is associated with COVID-19 is still an open question. Nonetheless, encouraging patients to quit smoking should be a priority because long-term sequelae of smoking have been linked to worsened or fatal COVID-19 cases, said Dr. Henry.

“There is a lack of definitive data on smoking to date. Nonetheless, we do know that many illnesses associated with smoking, such as [chronic obstructive pulmonary disease, hypertension, and heart disease are all strong risk factors for severe and fatal COVID-19,” he said. “Thus, absolutely we should encourage the public to quit smoking, especially for older individuals and those with comorbidities.”

The papers by Lippi et al., Vardavas et al., and Brake et al. had no funding source, and the authors reported no relevant conflicts of interest.

Evidence on the link between smoking and the likelihood of developing COVID-19 remains unclear to date, but quitting smoking is likely to lower the risk of developing more severe or fatal cases of the infection, according to research from several recent papers.

bilderbox/fotolia.com

Interest in how tobacco use affects COVID-19 infection rates stems from research showing that men at the epicenter of the outbreak in China having a higher early mortality rate. Early reports from China showed a case fatality rate of 4.7% for men, compared with 2.8% for women, according to the World Health Organization. The virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2, is suspected to enter a cell using the ACE2 receptor. Since smoking up-regulates this receptor, one popular theory is that smoking can increase the risk of COVID-19 or exacerbate symptoms of an existing infection (Eur Respir J. 2020 Apr 8. doi: 10.1183/13993003.00688-2020). In China, about half of men are active smokers, compared with 2.7% of women (Transl Lung Cancer Res. 2019;8[Suppl 1]:S21-30), so this association would explain the severe cases and increased mortality in this group. In response to potential risk for public health, the World Health Organization, Centers for Disease Control and Prevention, the Attorney General of Massachusetts, and other organizations have warned that smoking may increase one’s risk of transmitting and developing COVID-19 or may worsen the infection.

“While it is easy to jump to the conclusion that more ACE2 means more susceptibility to severe infection, there is no evidence to support this,” Brandon Michael Henry, MD, of the cardiac intensive care unit and the Heart Institute at Cincinnati Children’s Hospital Medical Center, said in an interview. “Moreover, some would argue (including myself) that increased ACE2 may in fact be protective, as ACE2 decreases the levels of angiotensin-2 which likely plays a significant role in the pathophysiology of ARDS.”

Some researchers have examined the limited evidence of smoking on COVID-19 risk and come to preliminary conclusions. In a letter to the editor recently published in the European Journal of Internal Medicine, Dr. Henry and Giuseppe Lippi, MD, of the section of clinical biochemistry in the department of neuroscience, biomedicine, and movement at the University of Verona (Italy), performed a meta-analysis of papers examining smoking and COVID-19 up to March 9, 2020 and identified five articles with 1,399 COVID-19 cases (Eur J Intern Med. 2020 Mar 16. doi: 10.1016/j.ejim.2020.03.014).

“Given the fact that COVID-19 is a primarily respiratory illness, smoking was one of first risk factors we examined,” Dr. Henry said.

They noted that a study by Liu et al. in the Chinese Medical Journal was the only paper that showed a significant association between smoking status and COVID-19 case severity (Chin Med J [Engl]. 2020 Feb 28. doi: 10.1097/CM9.0000000000000775), while the four other studies showed no significant association. The pooled data of all five studies showed an association that was not statistically significant (odds ratio, 1.69; 95% confidence interval, 0.41-6.92; P = .254). When Dr. Lippi and Dr. Henry performed the analysis again after removing a paper by Guan et al. (N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032) comprising 89.5% of patients in the pooled analysis, there was no significant association (OR, 4.35; 95% CI, 0.86-21.86; P = .129).

Constantine I. Vardavas, MD, FCCP, of the department of oral health policy and epidemiology at Harvard School of Dental Medicine, Boston, and Katerina Nikitara, of the University of Crete in Heraklion, Greece, also published a systematic review in Tobacco Induced Diseases of five studies evaluating smoking and COVID-19 (Tob Induc Dis. 2020. doi: 10.18332/tid/119324). Of the studies chosen for the review, four were shared with the paper by Dr. Lippi and Dr. Henry. They found “a higher percentage of smokers” made up severe COVID-19 cases, but acknowledged the majority of these were from the largest study by Guan et al. Overall, they calculated smokers carried a risk ratio of 1.4 (95% CI, 0.98-2.00) for developing severe COVID-19 symptoms, and were over twice as likely to be admitted to an ICU, require a mechanical ventilator, or die from COVID-19, compared with patients who did not smoke (RR, 2.4; 95% CI, 1.43-4.04).

“Although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19,” Dr. Vardavas and Ms. Nikitara concluded.

However, the association between smoking and severe disease was not significant, and it is not immediately clear how the analysis was performed based on the details in the editorial. “Both of our reports were limited by a lack of data adjusted for age, sex, and comorbidities which may influence any analysis on smoking,” Dr. Henry said.

Some researchers have proposed collecting information on smoking status and conducting further research on whether vaping devices like e-cigarettes also impact COVID-19 cases. An editorial by Samuel Brake and colleagues published in the Journal of Clinical Medicine proposed the ACE2-receptor binding site as an area of interest for COVID-19 and as a potential therapeutic target (J Clin Med. 2020 Mar 20. doi: 10.3390/jcm9030841).

Ultimately, whether smoking itself is associated with COVID-19 is still an open question. Nonetheless, encouraging patients to quit smoking should be a priority because long-term sequelae of smoking have been linked to worsened or fatal COVID-19 cases, said Dr. Henry.

“There is a lack of definitive data on smoking to date. Nonetheless, we do know that many illnesses associated with smoking, such as [chronic obstructive pulmonary disease, hypertension, and heart disease are all strong risk factors for severe and fatal COVID-19,” he said. “Thus, absolutely we should encourage the public to quit smoking, especially for older individuals and those with comorbidities.”

The papers by Lippi et al., Vardavas et al., and Brake et al. had no funding source, and the authors reported no relevant conflicts of interest.

Evidence on the link between smoking and the likelihood of developing COVID-19 remains unclear to date, but quitting smoking is likely to lower the risk of developing more severe or fatal cases of the infection, according to research from several recent papers.

bilderbox/fotolia.com

Interest in how tobacco use affects COVID-19 infection rates stems from research showing that men at the epicenter of the outbreak in China having a higher early mortality rate. Early reports from China showed a case fatality rate of 4.7% for men, compared with 2.8% for women, according to the World Health Organization. The virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2, is suspected to enter a cell using the ACE2 receptor. Since smoking up-regulates this receptor, one popular theory is that smoking can increase the risk of COVID-19 or exacerbate symptoms of an existing infection (Eur Respir J. 2020 Apr 8. doi: 10.1183/13993003.00688-2020). In China, about half of men are active smokers, compared with 2.7% of women (Transl Lung Cancer Res. 2019;8[Suppl 1]:S21-30), so this association would explain the severe cases and increased mortality in this group. In response to potential risk for public health, the World Health Organization, Centers for Disease Control and Prevention, the Attorney General of Massachusetts, and other organizations have warned that smoking may increase one’s risk of transmitting and developing COVID-19 or may worsen the infection.

“While it is easy to jump to the conclusion that more ACE2 means more susceptibility to severe infection, there is no evidence to support this,” Brandon Michael Henry, MD, of the cardiac intensive care unit and the Heart Institute at Cincinnati Children’s Hospital Medical Center, said in an interview. “Moreover, some would argue (including myself) that increased ACE2 may in fact be protective, as ACE2 decreases the levels of angiotensin-2 which likely plays a significant role in the pathophysiology of ARDS.”

Some researchers have examined the limited evidence of smoking on COVID-19 risk and come to preliminary conclusions. In a letter to the editor recently published in the European Journal of Internal Medicine, Dr. Henry and Giuseppe Lippi, MD, of the section of clinical biochemistry in the department of neuroscience, biomedicine, and movement at the University of Verona (Italy), performed a meta-analysis of papers examining smoking and COVID-19 up to March 9, 2020 and identified five articles with 1,399 COVID-19 cases (Eur J Intern Med. 2020 Mar 16. doi: 10.1016/j.ejim.2020.03.014).

“Given the fact that COVID-19 is a primarily respiratory illness, smoking was one of first risk factors we examined,” Dr. Henry said.

They noted that a study by Liu et al. in the Chinese Medical Journal was the only paper that showed a significant association between smoking status and COVID-19 case severity (Chin Med J [Engl]. 2020 Feb 28. doi: 10.1097/CM9.0000000000000775), while the four other studies showed no significant association. The pooled data of all five studies showed an association that was not statistically significant (odds ratio, 1.69; 95% confidence interval, 0.41-6.92; P = .254). When Dr. Lippi and Dr. Henry performed the analysis again after removing a paper by Guan et al. (N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032) comprising 89.5% of patients in the pooled analysis, there was no significant association (OR, 4.35; 95% CI, 0.86-21.86; P = .129).

Constantine I. Vardavas, MD, FCCP, of the department of oral health policy and epidemiology at Harvard School of Dental Medicine, Boston, and Katerina Nikitara, of the University of Crete in Heraklion, Greece, also published a systematic review in Tobacco Induced Diseases of five studies evaluating smoking and COVID-19 (Tob Induc Dis. 2020. doi: 10.18332/tid/119324). Of the studies chosen for the review, four were shared with the paper by Dr. Lippi and Dr. Henry. They found “a higher percentage of smokers” made up severe COVID-19 cases, but acknowledged the majority of these were from the largest study by Guan et al. Overall, they calculated smokers carried a risk ratio of 1.4 (95% CI, 0.98-2.00) for developing severe COVID-19 symptoms, and were over twice as likely to be admitted to an ICU, require a mechanical ventilator, or die from COVID-19, compared with patients who did not smoke (RR, 2.4; 95% CI, 1.43-4.04).

“Although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19,” Dr. Vardavas and Ms. Nikitara concluded.

However, the association between smoking and severe disease was not significant, and it is not immediately clear how the analysis was performed based on the details in the editorial. “Both of our reports were limited by a lack of data adjusted for age, sex, and comorbidities which may influence any analysis on smoking,” Dr. Henry said.

Some researchers have proposed collecting information on smoking status and conducting further research on whether vaping devices like e-cigarettes also impact COVID-19 cases. An editorial by Samuel Brake and colleagues published in the Journal of Clinical Medicine proposed the ACE2-receptor binding site as an area of interest for COVID-19 and as a potential therapeutic target (J Clin Med. 2020 Mar 20. doi: 10.3390/jcm9030841).

Ultimately, whether smoking itself is associated with COVID-19 is still an open question. Nonetheless, encouraging patients to quit smoking should be a priority because long-term sequelae of smoking have been linked to worsened or fatal COVID-19 cases, said Dr. Henry.

“There is a lack of definitive data on smoking to date. Nonetheless, we do know that many illnesses associated with smoking, such as [chronic obstructive pulmonary disease, hypertension, and heart disease are all strong risk factors for severe and fatal COVID-19,” he said. “Thus, absolutely we should encourage the public to quit smoking, especially for older individuals and those with comorbidities.”

The papers by Lippi et al., Vardavas et al., and Brake et al. had no funding source, and the authors reported no relevant conflicts of interest.