Journal of Clinical Outcomes Management

A minimally invasive multicancer blood test used with standard-of-care screening is safe, effective, and feasible for use in routine clinical care, according to interim findings from a large, prospective study.

The DETECT-A blood test, an early version of the CancerSEEK test currently in development, effectively guided patient management in real time, in some cases leading to diagnosis of early cancer and potentially curative surgery in asymptomatic women with no history of cancer.

Nickolas Papadopoulos, PhD, of Johns Hopkins Medicine in Baltimore, reported these findings at the AACR virtual meeting I. The findings were simultaneously published in Science.

The study enrolled 10,006 women, aged 65-75 years, with no prior cancer diagnosis. After exclusion and loss to follow-up, 9,911 women remained.

There were 26 patients who had cancer detected by the DETECT-A blood test, 15 of whom underwent follow-up PET-CT imaging and 9 of whom underwent surgical excision. An additional 24 cancers were detected by standard screening, and 46 were detected by other means.

The positive predictive value of the blood test was 19%. When the blood test was combined with imaging, the positive predictive value was 41%.
 

Improving upon standard screening

“Standard-of-care screening [was used] for three different organs: breast, lung, and colon. It was more sensitive for breast cancer,” Dr. Papadopoulos noted. “Blood testing, though, identified cancer in 10 different organs.”

In fact, the DETECT-A blood test detected 14 of 45 cancers in 7 organs for which no standard screening test is available.

In addition, 12 cancers in 3 organs (breast, lung, and colon) were first detected by DETECT-A rather than by standard screening. This increased the sensitivity of cancer detection from 47% with standard screening alone to 71% with standard screening plus blood testing.

“More important, 65% [of the cancers detected by blood test] were localized or regional, which have higher chance of successful treatment with intent to cure,” Dr. Papadopoulos said.

DETECT-A covers regions of 16 commonly mutated genes and 9 proteins known to be associated with cancer. In this study, 57% of cancers were detected by mutations.
 

Safety and additional screening

DETECT-A also proved safe, “without incurring a large number of futile invasive follow-up tests,” Dr. Papadopoulos said.

In fact, only 1% of patients without cancer underwent PET-CT imaging, and only 0.22% underwent a “futile” invasive follow-up procedure.

Three surgeries occurred in patients who were counted as false-positives, but the surgeries were determined to be indicated, Dr. Papadopoulos said. He explained that one was for large colonic polyps with high-grade dysplasia that could not be removed endoscopically, one was for an in situ carcinoma of the appendix, and one was for a 10-cm ovarian lesion that was found to be a mucinous cystadenoma.

The investigators also analyzed whether the availability of a “liquid biopsy” test like DETECT-A would inadvertently reduce patients’ use of standard screening and found that it did not. Mammography screening habits after receiving the baseline DETECT-A blood test did not differ significantly from those prior to study enrollment.

These findings are important because early detection is a key factor in reducing cancer-specific morbidity and mortality, and although minimally invasive screening tests, including liquid biopsies like DETECT-A, hold great promise, prospective clinical studies of these new methods are needed to ensure that the anticipated benefits outweigh the potential risks, Dr. Papadopoulos explained.

“The problem is that most cancers are detected at advanced stages when they are difficult to treat,” he said. “The earlier cancer is detected, the greater the chance of successful treatment.”
 

Unanswered questions and future studies

This study demonstrates that it is feasible for a minimally invasive blood test to safely detect multiple cancer types in patients without a history of cancer and to enable treatment with curative intent, at least in a subset of individuals, Dr. Papadopoulos said. He added that the findings also inform the design of future randomized trials “to establish clinical utility, cost-effectiveness, and benefit-to-risk ratio of future tests.”

Further studies will also be required to determine the clinical validity and utility of the strategy of using liquid biopsy as a complement to standard-of-care screening, Dr. Papadopoulos said.

Invited discussant David G. Huntsman, MD, of the University of British Columbia in Vancouver, applauded the investigators, saying this study serves to “move the field forward.” However, it still isn’t clear how sensitivity and negative predictive value will be determined and what the optimal testing schedule is.

“This is a prospective study that will provide the data on how this assay will be used [and] whether it should be used going forward,” Dr. Huntsman said, noting that the “much bigger and more important question” is whether it improves survival.

Cost-effectiveness will also be critical, he said.

This research was supported by The Marcus Foundation, Lustgarten Foundation for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, Susan Wojcicki and Dennis Troper, the Rolfe Foundation, The Conrad R. Hilton Foundation, The John Templeton Foundation, Burroughs Wellcome Career Award For Medical Scientists, and grants/contracts from the National Institutes of Health.

Dr. Papadopoulos disclosed relationships with Thrive Earlier Detection Inc., PGDx Inc., NeoPhore, Cage Pharma, and other companies. Dr. Huntsman is a founder, shareholder, and chief medical officer for Contextual Genomics.

[email protected]

SOURCE: Papadopoulos N et al. AACR 2020, Abstract CT022; Lennon AM et al. Science. 2020 Apr 28. pii: eabb9601. doi: 10.1126/science.abb9601.

A minimally invasive multicancer blood test used with standard-of-care screening is safe, effective, and feasible for use in routine clinical care, according to interim findings from a large, prospective study.

The DETECT-A blood test, an early version of the CancerSEEK test currently in development, effectively guided patient management in real time, in some cases leading to diagnosis of early cancer and potentially curative surgery in asymptomatic women with no history of cancer.

Nickolas Papadopoulos, PhD, of Johns Hopkins Medicine in Baltimore, reported these findings at the AACR virtual meeting I. The findings were simultaneously published in Science.

The study enrolled 10,006 women, aged 65-75 years, with no prior cancer diagnosis. After exclusion and loss to follow-up, 9,911 women remained.

There were 26 patients who had cancer detected by the DETECT-A blood test, 15 of whom underwent follow-up PET-CT imaging and 9 of whom underwent surgical excision. An additional 24 cancers were detected by standard screening, and 46 were detected by other means.

The positive predictive value of the blood test was 19%. When the blood test was combined with imaging, the positive predictive value was 41%.
 

Improving upon standard screening

“Standard-of-care screening [was used] for three different organs: breast, lung, and colon. It was more sensitive for breast cancer,” Dr. Papadopoulos noted. “Blood testing, though, identified cancer in 10 different organs.”

In fact, the DETECT-A blood test detected 14 of 45 cancers in 7 organs for which no standard screening test is available.

In addition, 12 cancers in 3 organs (breast, lung, and colon) were first detected by DETECT-A rather than by standard screening. This increased the sensitivity of cancer detection from 47% with standard screening alone to 71% with standard screening plus blood testing.

“More important, 65% [of the cancers detected by blood test] were localized or regional, which have higher chance of successful treatment with intent to cure,” Dr. Papadopoulos said.

DETECT-A covers regions of 16 commonly mutated genes and 9 proteins known to be associated with cancer. In this study, 57% of cancers were detected by mutations.
 

Safety and additional screening

DETECT-A also proved safe, “without incurring a large number of futile invasive follow-up tests,” Dr. Papadopoulos said.

In fact, only 1% of patients without cancer underwent PET-CT imaging, and only 0.22% underwent a “futile” invasive follow-up procedure.

Three surgeries occurred in patients who were counted as false-positives, but the surgeries were determined to be indicated, Dr. Papadopoulos said. He explained that one was for large colonic polyps with high-grade dysplasia that could not be removed endoscopically, one was for an in situ carcinoma of the appendix, and one was for a 10-cm ovarian lesion that was found to be a mucinous cystadenoma.

The investigators also analyzed whether the availability of a “liquid biopsy” test like DETECT-A would inadvertently reduce patients’ use of standard screening and found that it did not. Mammography screening habits after receiving the baseline DETECT-A blood test did not differ significantly from those prior to study enrollment.

These findings are important because early detection is a key factor in reducing cancer-specific morbidity and mortality, and although minimally invasive screening tests, including liquid biopsies like DETECT-A, hold great promise, prospective clinical studies of these new methods are needed to ensure that the anticipated benefits outweigh the potential risks, Dr. Papadopoulos explained.

“The problem is that most cancers are detected at advanced stages when they are difficult to treat,” he said. “The earlier cancer is detected, the greater the chance of successful treatment.”
 

Unanswered questions and future studies

This study demonstrates that it is feasible for a minimally invasive blood test to safely detect multiple cancer types in patients without a history of cancer and to enable treatment with curative intent, at least in a subset of individuals, Dr. Papadopoulos said. He added that the findings also inform the design of future randomized trials “to establish clinical utility, cost-effectiveness, and benefit-to-risk ratio of future tests.”

Further studies will also be required to determine the clinical validity and utility of the strategy of using liquid biopsy as a complement to standard-of-care screening, Dr. Papadopoulos said.

Invited discussant David G. Huntsman, MD, of the University of British Columbia in Vancouver, applauded the investigators, saying this study serves to “move the field forward.” However, it still isn’t clear how sensitivity and negative predictive value will be determined and what the optimal testing schedule is.

“This is a prospective study that will provide the data on how this assay will be used [and] whether it should be used going forward,” Dr. Huntsman said, noting that the “much bigger and more important question” is whether it improves survival.

Cost-effectiveness will also be critical, he said.

This research was supported by The Marcus Foundation, Lustgarten Foundation for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, Susan Wojcicki and Dennis Troper, the Rolfe Foundation, The Conrad R. Hilton Foundation, The John Templeton Foundation, Burroughs Wellcome Career Award For Medical Scientists, and grants/contracts from the National Institutes of Health.

Dr. Papadopoulos disclosed relationships with Thrive Earlier Detection Inc., PGDx Inc., NeoPhore, Cage Pharma, and other companies. Dr. Huntsman is a founder, shareholder, and chief medical officer for Contextual Genomics.

[email protected]

SOURCE: Papadopoulos N et al. AACR 2020, Abstract CT022; Lennon AM et al. Science. 2020 Apr 28. pii: eabb9601. doi: 10.1126/science.abb9601.

A minimally invasive multicancer blood test used with standard-of-care screening is safe, effective, and feasible for use in routine clinical care, according to interim findings from a large, prospective study.

The DETECT-A blood test, an early version of the CancerSEEK test currently in development, effectively guided patient management in real time, in some cases leading to diagnosis of early cancer and potentially curative surgery in asymptomatic women with no history of cancer.

Nickolas Papadopoulos, PhD, of Johns Hopkins Medicine in Baltimore, reported these findings at the AACR virtual meeting I. The findings were simultaneously published in Science.

The study enrolled 10,006 women, aged 65-75 years, with no prior cancer diagnosis. After exclusion and loss to follow-up, 9,911 women remained.

There were 26 patients who had cancer detected by the DETECT-A blood test, 15 of whom underwent follow-up PET-CT imaging and 9 of whom underwent surgical excision. An additional 24 cancers were detected by standard screening, and 46 were detected by other means.

The positive predictive value of the blood test was 19%. When the blood test was combined with imaging, the positive predictive value was 41%.
 

Improving upon standard screening

“Standard-of-care screening [was used] for three different organs: breast, lung, and colon. It was more sensitive for breast cancer,” Dr. Papadopoulos noted. “Blood testing, though, identified cancer in 10 different organs.”

In fact, the DETECT-A blood test detected 14 of 45 cancers in 7 organs for which no standard screening test is available.

In addition, 12 cancers in 3 organs (breast, lung, and colon) were first detected by DETECT-A rather than by standard screening. This increased the sensitivity of cancer detection from 47% with standard screening alone to 71% with standard screening plus blood testing.

“More important, 65% [of the cancers detected by blood test] were localized or regional, which have higher chance of successful treatment with intent to cure,” Dr. Papadopoulos said.

DETECT-A covers regions of 16 commonly mutated genes and 9 proteins known to be associated with cancer. In this study, 57% of cancers were detected by mutations.
 

Safety and additional screening

DETECT-A also proved safe, “without incurring a large number of futile invasive follow-up tests,” Dr. Papadopoulos said.

In fact, only 1% of patients without cancer underwent PET-CT imaging, and only 0.22% underwent a “futile” invasive follow-up procedure.

Three surgeries occurred in patients who were counted as false-positives, but the surgeries were determined to be indicated, Dr. Papadopoulos said. He explained that one was for large colonic polyps with high-grade dysplasia that could not be removed endoscopically, one was for an in situ carcinoma of the appendix, and one was for a 10-cm ovarian lesion that was found to be a mucinous cystadenoma.

The investigators also analyzed whether the availability of a “liquid biopsy” test like DETECT-A would inadvertently reduce patients’ use of standard screening and found that it did not. Mammography screening habits after receiving the baseline DETECT-A blood test did not differ significantly from those prior to study enrollment.

These findings are important because early detection is a key factor in reducing cancer-specific morbidity and mortality, and although minimally invasive screening tests, including liquid biopsies like DETECT-A, hold great promise, prospective clinical studies of these new methods are needed to ensure that the anticipated benefits outweigh the potential risks, Dr. Papadopoulos explained.

“The problem is that most cancers are detected at advanced stages when they are difficult to treat,” he said. “The earlier cancer is detected, the greater the chance of successful treatment.”
 

Unanswered questions and future studies

This study demonstrates that it is feasible for a minimally invasive blood test to safely detect multiple cancer types in patients without a history of cancer and to enable treatment with curative intent, at least in a subset of individuals, Dr. Papadopoulos said. He added that the findings also inform the design of future randomized trials “to establish clinical utility, cost-effectiveness, and benefit-to-risk ratio of future tests.”

Further studies will also be required to determine the clinical validity and utility of the strategy of using liquid biopsy as a complement to standard-of-care screening, Dr. Papadopoulos said.

Invited discussant David G. Huntsman, MD, of the University of British Columbia in Vancouver, applauded the investigators, saying this study serves to “move the field forward.” However, it still isn’t clear how sensitivity and negative predictive value will be determined and what the optimal testing schedule is.

“This is a prospective study that will provide the data on how this assay will be used [and] whether it should be used going forward,” Dr. Huntsman said, noting that the “much bigger and more important question” is whether it improves survival.

Cost-effectiveness will also be critical, he said.

This research was supported by The Marcus Foundation, Lustgarten Foundation for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, Susan Wojcicki and Dennis Troper, the Rolfe Foundation, The Conrad R. Hilton Foundation, The John Templeton Foundation, Burroughs Wellcome Career Award For Medical Scientists, and grants/contracts from the National Institutes of Health.

Dr. Papadopoulos disclosed relationships with Thrive Earlier Detection Inc., PGDx Inc., NeoPhore, Cage Pharma, and other companies. Dr. Huntsman is a founder, shareholder, and chief medical officer for Contextual Genomics.

[email protected]

SOURCE: Papadopoulos N et al. AACR 2020, Abstract CT022; Lennon AM et al. Science. 2020 Apr 28. pii: eabb9601. doi: 10.1126/science.abb9601.

Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.

During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.

The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.

The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.

“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.

Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).

Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.

The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.

A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.

As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.

Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.

Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.

At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.

The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.

The authors have disclosed no relevant financial relationships.

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

Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.

During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.

The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.

The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.

“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.

Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).

Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.

The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.

A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.

As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.

Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.

Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.

At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.

The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.

The authors have disclosed no relevant financial relationships.

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

Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.

During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.

The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.

The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.

“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.

Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).

Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.

The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.

A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.

As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.

Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.

Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.

At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.

The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.

The authors have disclosed no relevant financial relationships.

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

SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.

Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.

Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.

Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
 

Current research studies on COVID-19

Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.¹ In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.²

The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.³

Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.

The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.⁴

These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.

We are unaware of any current studies that are addressing the mental health needs of health care workers during the COVID-19 outbreak in United States. Future studies will become more critical in addressing this issue.

Risks to clinicians, families prevail

According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.⁵

Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.

A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.⁶ We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.⁷ Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.

Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.

Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition ^{from the field at a time when we most need all hands on deck.8}

Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.

Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.⁹ Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.¹⁰
 

Potential solutions for improving care

COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.⁹ Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.¹⁰

A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.¹¹ Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.^12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.

We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.¹⁴ This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.

For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.¹⁵

Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.

Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.¹⁶

Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.¹⁷ The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.¹⁸

These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.

In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.

The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.

We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.

Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.

References

1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.

2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.

3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.

4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.

5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.

6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.

7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.

8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.

9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.

10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.

11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.

12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.

13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.

14. Xiao H et al. Med Sci Monit. 2020;26:e923549.

15. Bergus GR et al. Acad Med. 2001;76:1148-52.

16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.

17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”

18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”

SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.

Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.

Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.

Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
 

Current research studies on COVID-19

Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.¹ In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.²

The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.³

Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.

The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.⁴

These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.

We are unaware of any current studies that are addressing the mental health needs of health care workers during the COVID-19 outbreak in United States. Future studies will become more critical in addressing this issue.

Risks to clinicians, families prevail

According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.⁵

Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.

A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.⁶ We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.⁷ Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.

Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.

Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition ^{from the field at a time when we most need all hands on deck.8}

Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.

Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.⁹ Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.¹⁰
 

Potential solutions for improving care

COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.⁹ Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.¹⁰

A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.¹¹ Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.^12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.

We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.¹⁴ This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.

For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.¹⁵

Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.

Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.¹⁶

Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.¹⁷ The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.¹⁸

These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.

In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.

The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.

We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.

Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.

References

1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.

2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.

3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.

4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.

5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.

6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.

7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.

8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.

9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.

10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.

11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.

12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.

13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.

14. Xiao H et al. Med Sci Monit. 2020;26:e923549.

15. Bergus GR et al. Acad Med. 2001;76:1148-52.

16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.

17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”

18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”

SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.

Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.

Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.

Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
 

Current research studies on COVID-19

Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.¹ In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.²

The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.³

Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.

The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.⁴

These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.

We are unaware of any current studies that are addressing the mental health needs of health care workers during the COVID-19 outbreak in United States. Future studies will become more critical in addressing this issue.

Risks to clinicians, families prevail

According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.⁵

Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.

A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.⁶ We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.⁷ Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.

Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.

Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition ^{from the field at a time when we most need all hands on deck.8}

Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.

Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.⁹ Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.¹⁰
 

Potential solutions for improving care

COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.⁹ Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.¹⁰

A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.¹¹ Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.^12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.

We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.¹⁴ This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.

For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.¹⁵

Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.

Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.¹⁶

Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.¹⁷ The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.¹⁸

These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.

In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.

The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.

We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.

Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.

References

1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.

2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.

3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.

4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.

5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.

6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.

7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.

8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.

9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.

10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.

11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.

12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.

13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.

14. Xiao H et al. Med Sci Monit. 2020;26:e923549.

15. Bergus GR et al. Acad Med. 2001;76:1148-52.

16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.

17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”

18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.

Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.

Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.

In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.

Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.

ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.

The haze of battle

Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.

Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.

Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.

Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.

Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”

His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
 

A moving target

Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.

The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.

Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).

Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.

Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.

On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.

To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.

Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.

[email protected]

This article was updated with the latest treatment algorithm on 5/6/2020.

Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.

Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.

Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.

In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.

Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.

ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.

The haze of battle

Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.

Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.

Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.

Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.

Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”

His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
 

A moving target

Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.

The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.

Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).

Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.

Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.

On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.

To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.

Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.

[email protected]

This article was updated with the latest treatment algorithm on 5/6/2020.

Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.

Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.

Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.

In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.

Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.

ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.

The haze of battle

Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.

Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.

Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.

Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.

Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”

His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
 

A moving target

Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.

The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.

Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).

Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.

Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.

On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.

To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.

Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.

[email protected]

This article was updated with the latest treatment algorithm on 5/6/2020.

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

With some pivotal trials on hold, the COVID-19 pandemic is slowing the pace of research in Alzheimer’s disease, stroke, and multiple sclerosis (MS).

However, researchers remain determined to forge ahead – with many redesigning their studies, at least in part to optimize the safety of their participants and research staff.

Keeping people engaged while protocols are on hold; expanding normal safety considerations; and re-enlisting statisticians to keep their findings as significant as possible are just some of study survival strategies underway.
 

Alzheimer’s disease research on hold

The pandemic is having a significant impact on Alzheimer’s disease research, and medical research in general, says Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association.

“Many clinical trials worldwide are pausing, changing, or halting the testing of the drug or the intervention,” she told Medscape Medical News. “How the teams have adapted depends on the study,” she added. “As you can imagine, things are changing on a daily basis.”

The US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) trial, for example, is on hold until at least May 31. The Alzheimer’s Association is helping to implement and fund the study along with Wake Forest University Medical Center.

“We’re not randomizing participants at this point in time and the intervention — which is based on a team meeting, and there is a social aspect to that — has been paused,” Dr. Snyder said.

Another pivotal study underway is the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (the A4 Study). Investigators are evaluating if an anti-amyloid antibody, solanezumab (Eli Lilly), can slow memory loss among people with amyloid on imaging but no symptoms of cognitive decline at baseline.

“The A4 Study is definitely continuing. However, in an effort to minimize risk to participants, site staff and study integrity, we have implemented an optional study hiatus for both the double-blind and open-label extension phases,” lead investigator Reisa Anne Sperling, MD, told Medscape Medical News.

“We wanted to prioritize the safety of our participants as well as the ability of participants to remain in the study … despite disruptions from the COVID-19 pandemic,” said Dr. Sperling, who is professor of neurology at Harvard Medical School and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston.

The ultimate goal is for A4 participants to receive the full number of planned infusions and assessments, even if it takes longer, she added.

Many Alzheimer’s disease researchers outside the United States face similar challenges. “As you probably are well aware, Spain is now in a complete lockdown. This has affected research centers like ours, the Barcelona Brain Research Center, and the way we work,” José Luís Molinuevo Guix, MD, PhD, told Medscape Medical News.

All participants in observational studies like the ALFA+ study and initiatives, as well as those in trials including PENSA and AB1601, “are not allowed, by law, to come in, hence from a safety perspective we are on good grounds,” added Dr. Molinuevo Guix, who directs the Alzheimer’s disease and other cognitive disorders unit at the Hospital Clinic de Barcelona.

The investigators are creating protocols for communicating with participants during the pandemic and for restarting visits safely after the lockdown has ended.
 

Stroke studies amended or suspended

A similar situation is occurring in stroke trials. Stroke is “obviously an acute disease, as well as a disease that requires secondary prevention,” Mitchell Elkind, MD, president-elect of the American Heart Association, told Medscape Medical News.

“One could argue that patients with stroke are going to be in the hospital anyway – why not enroll them in a study? They’re not incurring any additional risk,” he said. “But the staff have to come in to see them, and we’re really trying to avoid exposure.”

One ongoing trial, the Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA), stopped randomly assigning new participants to secondary prevention with apixaban or aspirin because of COVID-19. However, Dr. Elkind and colleagues plan to provide medication to the 440 people already in the trial.

“Wherever possible, the study coordinators are shipping the drug to people and doing follow-up visits by phone or video,” said Dr. Elkind, chief of the Division of Neurology Clinical Outcomes Research and Population Sciences at Columbia University in New York City.

Protecting patients, staff, and ultimately society is a “major driving force in stopping the randomizations,” he stressed.

ARCADIA is part of the StrokeNet prevention trials network, run by the NIH’s National Institute of Neurologic Disorders and Stroke (NINDS). Additional pivotal trials include the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) and the Multi-arm Optimization of Stroke Thrombolysis (MOST) studies, he said.

Joseph Broderick, MD, director of the national NIH StrokeNet, agreed that safety comes first. “It was the decision of the StrokeNet leadership and the principal investigators of the trials that we needed to hold recruitment of new patients while we worked on adapting processes of enrollment to ensure the safety of both patients and researchers interacting with study patients,” he told Medscape Medical News.

Potential risks vary based on the study intervention and the need for in-person interactions. Trials that include stimulation devices or physical therapy, for example, might be most affected, added Dr. Broderick, professor and director of the UC Gardner Neuroscience Institute at the University of Cincinnati in Ohio.

Nevertheless, “there are potential ways … to move as much as possible toward telemedicine and digital interactions during this time.”
 

Multiple challenges in multiple sclerosis

At the national level, the COVID-19 pandemic has had an “unprecedented impact on almost all the clinical trials funded by NINDS,” said Clinton Wright, MD, director of the Division of Clinical Research at NINDS. “Investigators have had to adapt quickly.”

Supplementing existing grants with money to conduct research on COVID-19 and pursuing research opportunities from different institutes are “some of the creative approaches [that] have come from the NIH [National Institutes of Health] itself,” Dr. Wright said. “Other creative approaches have come from investigators trying to keep their studies and trials going during the pandemic.”

In clinical trials, “everything from electronic consent to in-home research drug delivery is being brought to bear.”

“A few ongoing trials have been able to modify their protocols to obtain consent and carry out evaluations remotely by telephone or videoconferencing,” Dr. Wright said. “This is especially critical for trials that involve medical management of specific risk factors or conditions, where suspension of the trial could itself have adverse consequences due to reduced engagement with research participants.”

For participants already in MS studies, “each upcoming visit is assessed for whether it’s critical or could be done virtually or just skipped. If a person needs a treatment that cannot be postponed or skipped, they come in,” Jeffrey Cohen, MD, director of the Experimental Therapeutics Program at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, told Medscape Medical News.

New study enrollment is largely on hold and study visits for existing participants are limited, said Dr. Cohen, who is also president of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Some of the major ongoing trials in MS are “looking at very fundamental questions in the field,” Dr. Cohen said. The Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS) and Traditional Versus Early Aggressive Therapy for Multiple Sclerosis (TREAT-MS) trials, for example, evaluate whether treatment should be initiated with one of the less efficacious agents with escalation as needed, or whether treatment should begin with a high-efficacy agent.

Both trials are currently on hold because of the pandemic, as is the Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) study.

“There has been a lot of interest in hematopoietic stem cell transplants and where they fit into our overall treatment strategy, and this is intended to provide a more definitive answer,” Dr. Cohen said.
 

Making the most of down time

“The pandemic has been challenging” in terms of ongoing MS research, said Benjamin M. Segal, MD, chair of the Department of Neurology and director of the Neuroscience Research Institute at the Ohio State University Wexner Medical Center, Columbus.

“With regard to the lab, our animal model experiments have been placed on hold. We have stopped collecting samples from clinical subjects for biomarker studies.

“However, my research team has been taking advantage of the time that has been freed up from bench work by analyzing data sets that had been placed aside, delving more deeply into the literature, and writing new grant proposals and articles,” he added.

Two of Dr. Segal’s trainees are writing review articles on the immunopathogenesis of MS and its treatment. Another postdoctoral candidate is writing a grant proposal to investigate how coinfection with a coronavirus modulates CNS pathology and the clinical course of an animal model of MS.

“I am asking my trainees to plan out experiments further in advance than they ever have before, so they are as prepared as possible to resume their research agendas once we are up and running again,” Dr. Segal said.

Confronting current challenges while planning for a future less disrupted by the pandemic is a common theme that emerges.

“The duration of this [pandemic] will dictate how we analyze the data at the end [for the US POINTER study]. There is a large group of statisticians working on this,” Dr. Snyder said.

Dr. Sperling of Harvard Medical School also remains undeterred. “This is definitely a challenging time, as we must not allow the COVID-19 to interfere with our essential mission to find a successful treatment to prevent cognitive decline in AD. We do need, however, to be as flexible as possible to protect our participants and minimize the impact to our overall study integrity,” she said.
 

NIH guidance

Dr. Molinuevo Guix, of the Barcelona Brain Research Center, is also determined to continue his Alzheimer’s disease research. “I am aware that after the crisis, there will be less [risk] but still a COVID-19 infection risk, so apart from trying to generate part of our visits virtually, we want to make sure we have all necessary safety measures in place. We remain very active to preserve the work we have done to keep up the fight against Alzheimer’s and dementia,” he said.

Such forward thinking also applies to major stroke trials, said Dr. Broderick of the University of Cincinnati. “As soon as we shut down enrollment in stroke trials, we immediately began to make plans about how and when we can restart our stroke trials,” he explained. “One of our trials can do every step of the trial process remotely without direct in-person interactions and will be able to restart soon.”

An individualized approach is needed, Dr. Broderick added. “For trials involving necessary in-person and hands-on assessments, we will need to consider how best to use protective equipment and expanded testing that will likely match the ongoing clinical care and requirements at a given institution.

“Even if a trial officially reopens enrollment, the decision to enroll locally will need to follow local institutional environment and guidelines. Thus, restart of trial enrollment will not likely be uniform, similar to how trials often start in the first place,” Dr. Broderick said.

The NIH published uniform standards for researchers across its institutes to help guide them during the pandemic. Future contingency plans also are underway at the NINDS.

“As the pandemic wanes and in-person research activities restart, it will be important to have in place safety measures that prevent a resurgence of the virus, such as proper personal protective equipment for staff and research participants, said Dr. Wright, the clinical research director at NINDS.

For clinical trials, NINDS is prepared to provide supplemental funds to trial investigators to help support additional activities undertaken as a result of the pandemic.

“This has been an instructive experience. The pandemic will end, and we will resume much of our old patterns of behavior,” said Ohio State’s Dr. Segal. “But some of the strategies that we have employed to get through this time will continue to influence the way we communicate information, plan experiments, and prioritize research activities in the future, to good effect.”

Drs. Snyder, Sperling, Molinuevo Guix, Elkind, Broderick, Wright, Cohen, and Segal have disclosed no relevant disclosures.

This story first appeared on Medscape.com.

With some pivotal trials on hold, the COVID-19 pandemic is slowing the pace of research in Alzheimer’s disease, stroke, and multiple sclerosis (MS).

However, researchers remain determined to forge ahead – with many redesigning their studies, at least in part to optimize the safety of their participants and research staff.

Keeping people engaged while protocols are on hold; expanding normal safety considerations; and re-enlisting statisticians to keep their findings as significant as possible are just some of study survival strategies underway.
 

Alzheimer’s disease research on hold

The pandemic is having a significant impact on Alzheimer’s disease research, and medical research in general, says Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association.

“Many clinical trials worldwide are pausing, changing, or halting the testing of the drug or the intervention,” she told Medscape Medical News. “How the teams have adapted depends on the study,” she added. “As you can imagine, things are changing on a daily basis.”

The US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) trial, for example, is on hold until at least May 31. The Alzheimer’s Association is helping to implement and fund the study along with Wake Forest University Medical Center.

“We’re not randomizing participants at this point in time and the intervention — which is based on a team meeting, and there is a social aspect to that — has been paused,” Dr. Snyder said.

Another pivotal study underway is the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (the A4 Study). Investigators are evaluating if an anti-amyloid antibody, solanezumab (Eli Lilly), can slow memory loss among people with amyloid on imaging but no symptoms of cognitive decline at baseline.

“The A4 Study is definitely continuing. However, in an effort to minimize risk to participants, site staff and study integrity, we have implemented an optional study hiatus for both the double-blind and open-label extension phases,” lead investigator Reisa Anne Sperling, MD, told Medscape Medical News.

“We wanted to prioritize the safety of our participants as well as the ability of participants to remain in the study … despite disruptions from the COVID-19 pandemic,” said Dr. Sperling, who is professor of neurology at Harvard Medical School and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston.

The ultimate goal is for A4 participants to receive the full number of planned infusions and assessments, even if it takes longer, she added.

Many Alzheimer’s disease researchers outside the United States face similar challenges. “As you probably are well aware, Spain is now in a complete lockdown. This has affected research centers like ours, the Barcelona Brain Research Center, and the way we work,” José Luís Molinuevo Guix, MD, PhD, told Medscape Medical News.

All participants in observational studies like the ALFA+ study and initiatives, as well as those in trials including PENSA and AB1601, “are not allowed, by law, to come in, hence from a safety perspective we are on good grounds,” added Dr. Molinuevo Guix, who directs the Alzheimer’s disease and other cognitive disorders unit at the Hospital Clinic de Barcelona.

The investigators are creating protocols for communicating with participants during the pandemic and for restarting visits safely after the lockdown has ended.
 

Stroke studies amended or suspended

A similar situation is occurring in stroke trials. Stroke is “obviously an acute disease, as well as a disease that requires secondary prevention,” Mitchell Elkind, MD, president-elect of the American Heart Association, told Medscape Medical News.

“One could argue that patients with stroke are going to be in the hospital anyway – why not enroll them in a study? They’re not incurring any additional risk,” he said. “But the staff have to come in to see them, and we’re really trying to avoid exposure.”

One ongoing trial, the Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA), stopped randomly assigning new participants to secondary prevention with apixaban or aspirin because of COVID-19. However, Dr. Elkind and colleagues plan to provide medication to the 440 people already in the trial.

“Wherever possible, the study coordinators are shipping the drug to people and doing follow-up visits by phone or video,” said Dr. Elkind, chief of the Division of Neurology Clinical Outcomes Research and Population Sciences at Columbia University in New York City.

Protecting patients, staff, and ultimately society is a “major driving force in stopping the randomizations,” he stressed.

ARCADIA is part of the StrokeNet prevention trials network, run by the NIH’s National Institute of Neurologic Disorders and Stroke (NINDS). Additional pivotal trials include the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) and the Multi-arm Optimization of Stroke Thrombolysis (MOST) studies, he said.

Joseph Broderick, MD, director of the national NIH StrokeNet, agreed that safety comes first. “It was the decision of the StrokeNet leadership and the principal investigators of the trials that we needed to hold recruitment of new patients while we worked on adapting processes of enrollment to ensure the safety of both patients and researchers interacting with study patients,” he told Medscape Medical News.

Potential risks vary based on the study intervention and the need for in-person interactions. Trials that include stimulation devices or physical therapy, for example, might be most affected, added Dr. Broderick, professor and director of the UC Gardner Neuroscience Institute at the University of Cincinnati in Ohio.

Nevertheless, “there are potential ways … to move as much as possible toward telemedicine and digital interactions during this time.”
 

Multiple challenges in multiple sclerosis

At the national level, the COVID-19 pandemic has had an “unprecedented impact on almost all the clinical trials funded by NINDS,” said Clinton Wright, MD, director of the Division of Clinical Research at NINDS. “Investigators have had to adapt quickly.”

Supplementing existing grants with money to conduct research on COVID-19 and pursuing research opportunities from different institutes are “some of the creative approaches [that] have come from the NIH [National Institutes of Health] itself,” Dr. Wright said. “Other creative approaches have come from investigators trying to keep their studies and trials going during the pandemic.”

In clinical trials, “everything from electronic consent to in-home research drug delivery is being brought to bear.”

“A few ongoing trials have been able to modify their protocols to obtain consent and carry out evaluations remotely by telephone or videoconferencing,” Dr. Wright said. “This is especially critical for trials that involve medical management of specific risk factors or conditions, where suspension of the trial could itself have adverse consequences due to reduced engagement with research participants.”

For participants already in MS studies, “each upcoming visit is assessed for whether it’s critical or could be done virtually or just skipped. If a person needs a treatment that cannot be postponed or skipped, they come in,” Jeffrey Cohen, MD, director of the Experimental Therapeutics Program at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, told Medscape Medical News.

New study enrollment is largely on hold and study visits for existing participants are limited, said Dr. Cohen, who is also president of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Some of the major ongoing trials in MS are “looking at very fundamental questions in the field,” Dr. Cohen said. The Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS) and Traditional Versus Early Aggressive Therapy for Multiple Sclerosis (TREAT-MS) trials, for example, evaluate whether treatment should be initiated with one of the less efficacious agents with escalation as needed, or whether treatment should begin with a high-efficacy agent.

Both trials are currently on hold because of the pandemic, as is the Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) study.

“There has been a lot of interest in hematopoietic stem cell transplants and where they fit into our overall treatment strategy, and this is intended to provide a more definitive answer,” Dr. Cohen said.
 

Making the most of down time

“The pandemic has been challenging” in terms of ongoing MS research, said Benjamin M. Segal, MD, chair of the Department of Neurology and director of the Neuroscience Research Institute at the Ohio State University Wexner Medical Center, Columbus.

“With regard to the lab, our animal model experiments have been placed on hold. We have stopped collecting samples from clinical subjects for biomarker studies.

“However, my research team has been taking advantage of the time that has been freed up from bench work by analyzing data sets that had been placed aside, delving more deeply into the literature, and writing new grant proposals and articles,” he added.

Two of Dr. Segal’s trainees are writing review articles on the immunopathogenesis of MS and its treatment. Another postdoctoral candidate is writing a grant proposal to investigate how coinfection with a coronavirus modulates CNS pathology and the clinical course of an animal model of MS.

“I am asking my trainees to plan out experiments further in advance than they ever have before, so they are as prepared as possible to resume their research agendas once we are up and running again,” Dr. Segal said.

Confronting current challenges while planning for a future less disrupted by the pandemic is a common theme that emerges.

“The duration of this [pandemic] will dictate how we analyze the data at the end [for the US POINTER study]. There is a large group of statisticians working on this,” Dr. Snyder said.

Dr. Sperling of Harvard Medical School also remains undeterred. “This is definitely a challenging time, as we must not allow the COVID-19 to interfere with our essential mission to find a successful treatment to prevent cognitive decline in AD. We do need, however, to be as flexible as possible to protect our participants and minimize the impact to our overall study integrity,” she said.
 

NIH guidance

Dr. Molinuevo Guix, of the Barcelona Brain Research Center, is also determined to continue his Alzheimer’s disease research. “I am aware that after the crisis, there will be less [risk] but still a COVID-19 infection risk, so apart from trying to generate part of our visits virtually, we want to make sure we have all necessary safety measures in place. We remain very active to preserve the work we have done to keep up the fight against Alzheimer’s and dementia,” he said.

Such forward thinking also applies to major stroke trials, said Dr. Broderick of the University of Cincinnati. “As soon as we shut down enrollment in stroke trials, we immediately began to make plans about how and when we can restart our stroke trials,” he explained. “One of our trials can do every step of the trial process remotely without direct in-person interactions and will be able to restart soon.”

An individualized approach is needed, Dr. Broderick added. “For trials involving necessary in-person and hands-on assessments, we will need to consider how best to use protective equipment and expanded testing that will likely match the ongoing clinical care and requirements at a given institution.

“Even if a trial officially reopens enrollment, the decision to enroll locally will need to follow local institutional environment and guidelines. Thus, restart of trial enrollment will not likely be uniform, similar to how trials often start in the first place,” Dr. Broderick said.

The NIH published uniform standards for researchers across its institutes to help guide them during the pandemic. Future contingency plans also are underway at the NINDS.

“As the pandemic wanes and in-person research activities restart, it will be important to have in place safety measures that prevent a resurgence of the virus, such as proper personal protective equipment for staff and research participants, said Dr. Wright, the clinical research director at NINDS.

For clinical trials, NINDS is prepared to provide supplemental funds to trial investigators to help support additional activities undertaken as a result of the pandemic.

“This has been an instructive experience. The pandemic will end, and we will resume much of our old patterns of behavior,” said Ohio State’s Dr. Segal. “But some of the strategies that we have employed to get through this time will continue to influence the way we communicate information, plan experiments, and prioritize research activities in the future, to good effect.”

Drs. Snyder, Sperling, Molinuevo Guix, Elkind, Broderick, Wright, Cohen, and Segal have disclosed no relevant disclosures.

This story first appeared on Medscape.com.

With some pivotal trials on hold, the COVID-19 pandemic is slowing the pace of research in Alzheimer’s disease, stroke, and multiple sclerosis (MS).

However, researchers remain determined to forge ahead – with many redesigning their studies, at least in part to optimize the safety of their participants and research staff.

Keeping people engaged while protocols are on hold; expanding normal safety considerations; and re-enlisting statisticians to keep their findings as significant as possible are just some of study survival strategies underway.
 

Alzheimer’s disease research on hold

The pandemic is having a significant impact on Alzheimer’s disease research, and medical research in general, says Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association.

“Many clinical trials worldwide are pausing, changing, or halting the testing of the drug or the intervention,” she told Medscape Medical News. “How the teams have adapted depends on the study,” she added. “As you can imagine, things are changing on a daily basis.”

The US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) trial, for example, is on hold until at least May 31. The Alzheimer’s Association is helping to implement and fund the study along with Wake Forest University Medical Center.

“We’re not randomizing participants at this point in time and the intervention — which is based on a team meeting, and there is a social aspect to that — has been paused,” Dr. Snyder said.

Another pivotal study underway is the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (the A4 Study). Investigators are evaluating if an anti-amyloid antibody, solanezumab (Eli Lilly), can slow memory loss among people with amyloid on imaging but no symptoms of cognitive decline at baseline.

“The A4 Study is definitely continuing. However, in an effort to minimize risk to participants, site staff and study integrity, we have implemented an optional study hiatus for both the double-blind and open-label extension phases,” lead investigator Reisa Anne Sperling, MD, told Medscape Medical News.

“We wanted to prioritize the safety of our participants as well as the ability of participants to remain in the study … despite disruptions from the COVID-19 pandemic,” said Dr. Sperling, who is professor of neurology at Harvard Medical School and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston.

The ultimate goal is for A4 participants to receive the full number of planned infusions and assessments, even if it takes longer, she added.

Many Alzheimer’s disease researchers outside the United States face similar challenges. “As you probably are well aware, Spain is now in a complete lockdown. This has affected research centers like ours, the Barcelona Brain Research Center, and the way we work,” José Luís Molinuevo Guix, MD, PhD, told Medscape Medical News.

All participants in observational studies like the ALFA+ study and initiatives, as well as those in trials including PENSA and AB1601, “are not allowed, by law, to come in, hence from a safety perspective we are on good grounds,” added Dr. Molinuevo Guix, who directs the Alzheimer’s disease and other cognitive disorders unit at the Hospital Clinic de Barcelona.

The investigators are creating protocols for communicating with participants during the pandemic and for restarting visits safely after the lockdown has ended.
 

Stroke studies amended or suspended

A similar situation is occurring in stroke trials. Stroke is “obviously an acute disease, as well as a disease that requires secondary prevention,” Mitchell Elkind, MD, president-elect of the American Heart Association, told Medscape Medical News.

“One could argue that patients with stroke are going to be in the hospital anyway – why not enroll them in a study? They’re not incurring any additional risk,” he said. “But the staff have to come in to see them, and we’re really trying to avoid exposure.”

One ongoing trial, the Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA), stopped randomly assigning new participants to secondary prevention with apixaban or aspirin because of COVID-19. However, Dr. Elkind and colleagues plan to provide medication to the 440 people already in the trial.

“Wherever possible, the study coordinators are shipping the drug to people and doing follow-up visits by phone or video,” said Dr. Elkind, chief of the Division of Neurology Clinical Outcomes Research and Population Sciences at Columbia University in New York City.

Protecting patients, staff, and ultimately society is a “major driving force in stopping the randomizations,” he stressed.

ARCADIA is part of the StrokeNet prevention trials network, run by the NIH’s National Institute of Neurologic Disorders and Stroke (NINDS). Additional pivotal trials include the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) and the Multi-arm Optimization of Stroke Thrombolysis (MOST) studies, he said.

Joseph Broderick, MD, director of the national NIH StrokeNet, agreed that safety comes first. “It was the decision of the StrokeNet leadership and the principal investigators of the trials that we needed to hold recruitment of new patients while we worked on adapting processes of enrollment to ensure the safety of both patients and researchers interacting with study patients,” he told Medscape Medical News.

Potential risks vary based on the study intervention and the need for in-person interactions. Trials that include stimulation devices or physical therapy, for example, might be most affected, added Dr. Broderick, professor and director of the UC Gardner Neuroscience Institute at the University of Cincinnati in Ohio.

Nevertheless, “there are potential ways … to move as much as possible toward telemedicine and digital interactions during this time.”
 

Multiple challenges in multiple sclerosis

At the national level, the COVID-19 pandemic has had an “unprecedented impact on almost all the clinical trials funded by NINDS,” said Clinton Wright, MD, director of the Division of Clinical Research at NINDS. “Investigators have had to adapt quickly.”

Supplementing existing grants with money to conduct research on COVID-19 and pursuing research opportunities from different institutes are “some of the creative approaches [that] have come from the NIH [National Institutes of Health] itself,” Dr. Wright said. “Other creative approaches have come from investigators trying to keep their studies and trials going during the pandemic.”

In clinical trials, “everything from electronic consent to in-home research drug delivery is being brought to bear.”

“A few ongoing trials have been able to modify their protocols to obtain consent and carry out evaluations remotely by telephone or videoconferencing,” Dr. Wright said. “This is especially critical for trials that involve medical management of specific risk factors or conditions, where suspension of the trial could itself have adverse consequences due to reduced engagement with research participants.”

For participants already in MS studies, “each upcoming visit is assessed for whether it’s critical or could be done virtually or just skipped. If a person needs a treatment that cannot be postponed or skipped, they come in,” Jeffrey Cohen, MD, director of the Experimental Therapeutics Program at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, told Medscape Medical News.

New study enrollment is largely on hold and study visits for existing participants are limited, said Dr. Cohen, who is also president of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Some of the major ongoing trials in MS are “looking at very fundamental questions in the field,” Dr. Cohen said. The Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS) and Traditional Versus Early Aggressive Therapy for Multiple Sclerosis (TREAT-MS) trials, for example, evaluate whether treatment should be initiated with one of the less efficacious agents with escalation as needed, or whether treatment should begin with a high-efficacy agent.

Both trials are currently on hold because of the pandemic, as is the Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) study.

“There has been a lot of interest in hematopoietic stem cell transplants and where they fit into our overall treatment strategy, and this is intended to provide a more definitive answer,” Dr. Cohen said.
 

Making the most of down time

“The pandemic has been challenging” in terms of ongoing MS research, said Benjamin M. Segal, MD, chair of the Department of Neurology and director of the Neuroscience Research Institute at the Ohio State University Wexner Medical Center, Columbus.

“With regard to the lab, our animal model experiments have been placed on hold. We have stopped collecting samples from clinical subjects for biomarker studies.

“However, my research team has been taking advantage of the time that has been freed up from bench work by analyzing data sets that had been placed aside, delving more deeply into the literature, and writing new grant proposals and articles,” he added.

Two of Dr. Segal’s trainees are writing review articles on the immunopathogenesis of MS and its treatment. Another postdoctoral candidate is writing a grant proposal to investigate how coinfection with a coronavirus modulates CNS pathology and the clinical course of an animal model of MS.

“I am asking my trainees to plan out experiments further in advance than they ever have before, so they are as prepared as possible to resume their research agendas once we are up and running again,” Dr. Segal said.

Confronting current challenges while planning for a future less disrupted by the pandemic is a common theme that emerges.

“The duration of this [pandemic] will dictate how we analyze the data at the end [for the US POINTER study]. There is a large group of statisticians working on this,” Dr. Snyder said.

Dr. Sperling of Harvard Medical School also remains undeterred. “This is definitely a challenging time, as we must not allow the COVID-19 to interfere with our essential mission to find a successful treatment to prevent cognitive decline in AD. We do need, however, to be as flexible as possible to protect our participants and minimize the impact to our overall study integrity,” she said.
 

NIH guidance

Dr. Molinuevo Guix, of the Barcelona Brain Research Center, is also determined to continue his Alzheimer’s disease research. “I am aware that after the crisis, there will be less [risk] but still a COVID-19 infection risk, so apart from trying to generate part of our visits virtually, we want to make sure we have all necessary safety measures in place. We remain very active to preserve the work we have done to keep up the fight against Alzheimer’s and dementia,” he said.

Such forward thinking also applies to major stroke trials, said Dr. Broderick of the University of Cincinnati. “As soon as we shut down enrollment in stroke trials, we immediately began to make plans about how and when we can restart our stroke trials,” he explained. “One of our trials can do every step of the trial process remotely without direct in-person interactions and will be able to restart soon.”

An individualized approach is needed, Dr. Broderick added. “For trials involving necessary in-person and hands-on assessments, we will need to consider how best to use protective equipment and expanded testing that will likely match the ongoing clinical care and requirements at a given institution.

“Even if a trial officially reopens enrollment, the decision to enroll locally will need to follow local institutional environment and guidelines. Thus, restart of trial enrollment will not likely be uniform, similar to how trials often start in the first place,” Dr. Broderick said.

The NIH published uniform standards for researchers across its institutes to help guide them during the pandemic. Future contingency plans also are underway at the NINDS.

“As the pandemic wanes and in-person research activities restart, it will be important to have in place safety measures that prevent a resurgence of the virus, such as proper personal protective equipment for staff and research participants, said Dr. Wright, the clinical research director at NINDS.

For clinical trials, NINDS is prepared to provide supplemental funds to trial investigators to help support additional activities undertaken as a result of the pandemic.

“This has been an instructive experience. The pandemic will end, and we will resume much of our old patterns of behavior,” said Ohio State’s Dr. Segal. “But some of the strategies that we have employed to get through this time will continue to influence the way we communicate information, plan experiments, and prioritize research activities in the future, to good effect.”

Drs. Snyder, Sperling, Molinuevo Guix, Elkind, Broderick, Wright, Cohen, and Segal have disclosed no relevant disclosures.

This story first appeared on Medscape.com.