Infectious Disease Practitioner

Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

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Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

[email protected]

Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

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Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

Patients with B-cell lymphoma are immunocompromised because of the disease and its treatments. This presents the question of their outcomes upon infection with SARS-CoV-2. Researchers assessed the characteristics of patients with lymphoma hospitalized for COVID-19 and analyzed determinants of mortality in a retrospective database study. The investigators looked at data from adult patients with lymphoma who were hospitalized for COVID-19 in March and April 2020 in three French regions.

CoRus13/Wikimedia Commons/Creative Commons 4.0

Older age and relapsed/refractory (r/r) disease in B-cell lymphoma patients were both found to be independent risk factors of increased death rate from COVID-19, according to the online report in EClinicalMedicine, published by The Lancet.

These results encourage “the application of standard Covid-19 treatment, including intubation, for lymphoma patients with Covid-19 lymphoma diagnosis, under first- or second-line chemotherapy, or in remission,” according to Sylvain Lamure, MD, of Montellier (France) University, and colleagues.

The study examined a series of 89 consecutive patients from three French regions who had lymphoma and were hospitalized for COVID-19 in March and April 2020. The population was homogeneous; most patients were diagnosed with B-cell non-Hodgkin lymphoma (NHL) and had been treated for their lymphoma within 1 year.
 

Promising results for many

There were a significant associations between 30-day mortality and increasing age (over age 70 years) and r/r lymphoma. However, in the absence of those factors, mortality of the lymphoma patients with COVID-19 was comparable with that of the reference French COVID-19 population. In addition, there was no significant impact of active lymphoma treatment that had been given within 1 year, except for those patients who received bendamustine, which was associated with greater mortality, according to the researchers.

With a median follow-up of 33 days from admission, the Kaplan-Meier estimate of 30-day overall survival was 71% (95% confidence interval, 62%-81%). According to histological type of the lymphoma, 30-day overall survival rates were 80% (95% CI, 45%-100%) for Hodgkin lymphoma, 71% (95% CI, 61%-82%) for B-cell non-Hodgkin Lymphoma, and 71% (95% CI, 38%-100%) for T-cell non-Hodgkin Lymphoma.

The main factors associated with mortality were age 70 years and older (hazard ratio, 3.78; 95% CI, 1.73-8.25; P = .0009), hypertension (HR, 2.20; 95% CI, 1.06-4.59; P = .03), previous cancer (HR, 2.11; 95% CI, 0.90-4.92; P = .08), use of bendamustine within 12 months before admission to hospital (HR, 3.05; 95% CI, 1.31-7.11; P = .01), and r/r lymphoma (HR, 2.62; 95% CI, 1.20-5.72; P = .02).

Overall, the Kaplan-Meier estimates of 30-day overall survival were 61% for patients with r/r lymphoma, 52% in patients age 70 years with non–r/r lymphoma, and 88% for patients younger than 70 years with non–r/r, which was comparable with general population survival data among French populations, according to the researchers.

“Longer term clinical follow-up and biological monitoring of immune responses is warranted to explore the impact of lymphoma and its treatment on the immunity and prolonged outcome of Covid-19 patients,” they concluded.

The study was unsponsored. Several of the authors reported financial relationships with a number of biotechnology and pharmaceutical companies.

[email protected]

SOURCE: Lamure S et al. EClinicalMedicine. 2020 Oct 12. doi: 10.1016/j.eclinm.2020.100549.

We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.

“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.

Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.

We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”

Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?

When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.

In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.

“Early administration of high-dose enteral vitamin D₃ did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.

In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.

“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
 

Maintenance dose needed?

One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.

In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.

The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”

“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”

Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.

Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).

Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.

“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.

Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.

“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”

However, “we’re not really sure that it improves outcomes,” he said.
 

A chronic issue?

“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.

“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.

“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.

Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.

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

We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.

“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.

Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.

We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”

Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?

When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.

In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.

“Early administration of high-dose enteral vitamin D₃ did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.

In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.

“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
 

Maintenance dose needed?

One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.

In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.

The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”

“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”

Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.

Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).

Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.

“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.

Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.

“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”

However, “we’re not really sure that it improves outcomes,” he said.
 

A chronic issue?

“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.

“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.

“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.

Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.

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

We can “stop putting money on vitamin D” to help patients who require critical care, said Todd Rice, MD, FCCP.

“Results from vitamin D trials have not been uniformly one way, but they have been pretty uniformly disappointing,” Dr. Rice, from Vanderbilt University Medical Center, Nashville, Tenn., reported at the annual meeting of the American College of Chest Physicians.

Low levels of vitamin D in critically ill COVID-19 patients have been reported in numerous recent studies, and researchers are looking for ways to boost those levels and improve outcomes.

We are seeing “the exact same story” in the critically ill COVID-19 population as we see in the general ICU population, said Dr. Rice. “The whole scenario is repeating itself. I’m pessimistic.”

Still, vitamin D levels can be elevated so, in theory, “the concept makes sense,” he said. There is evidence that, “when given enterally, the levels rise nicely” and vitamin D is absorbed reasonably well.” But is that enough?

When patients are admitted to the ICU, some biomarkers in the body are too high and others are too low. Vitamin D is often too low. So far, though, “supplementing vitamin D in the ICU has not significantly improved outcomes,” said Dr. Rice.

In the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, Dr. Rice and colleagues found no statistical benefit when a 540,000 IU boost of vitamin D was administered to 2,624 critically ill patients, as reported by Medscape Medical News.

“Early administration of high-dose enteral vitamin D₃ did not provide an advantage over placebo with respect to 90-day mortality or other nonfatal outcomes among critically ill, vitamin D–deficient patients,” the researchers write in their recent report.

In fact, VIOLET ended before enrollment had reached the planned 3,000-patient cohort because the statistical analysis clearly did not show benefit. Those enrolled were in the ICU because of, among other things, pneumonia, sepsis, the need for mechanical ventilation or vasopressors, and risk for acute respiratory distress syndrome.

“It doesn’t look like vitamin D is going to be the answer to our critical care problems,” Dr. Rice said in an interview.
 

Maintenance dose needed?

One theory suggests that VIOLET might have failed because a maintenance dose is needed after the initial boost of vitamin D.

In the ongoing VITDALIZE trial, critically ill patients with severe vitamin D deficiency (12 ng/mL or less at admission) receive an initial 540,000-IU dose followed by 4,000 IU per day.

The highly anticipated VITDALIZE results are expected in the middle of next year, Dr. Rice reported, so “let’s wait to see.”

“Vitamin D may not have an acute effect,” he theorized. “We can raise your levels, but that doesn’t give you all the benefits of having a sufficient level for a long period of time.”

Another theory suggests that a low level of vitamin D is simply a signal of the severity of disease, not a direct influence on disease pathology.

Some observational data have shown an association between low levels of vitamin D and outcomes in COVID-19 patients (Nutrients. 2020 May 9;12[5]:1359; medRxiv 2020 Apr 24. doi: 10.1101/2020.04.24.20075838; JAMA Netw Open. 2020;3[9]:e2019722; FEBS J. 2020 Jul 23;10.1111/febs.15495; Clin Endocrinol [Oxf]. 2020 Jul 3;10.1111/cen.14276), but some have shown no association (medRxiv. 2020 Jun 26. doi: 10.1101/2020.06.26.20140921; J Public Health [Oxf]. 2020 Aug 18;42[3]:451-60).

Dr. Rice conducted a search of Clinicaltrials.gov immediately before his presentation on Sunday, and found 41 ongoing interventional studies – “not observational studies” – looking at COVID-19 and vitamin D.

“They’re recruiting, they’re enrolling; hopefully we’ll have data soon,” he said.

Researchers have checked a lot of boxes with a resounding yes on the vitamin D question, so there’s reason to think an association does exist for ICU patients, whether or not they have COVID-19.

“Is there a theoretical benefit of vitamin D in the ICU?” Dr. Rice asked. “Yes. Is vitamin D deficient in patients in the ICU? Yes. Is that deficiency associated with poor outcomes? Yes. Can it be replaced safely? Yes.”

However, “we’re not really sure that it improves outcomes,” he said.
 

A chronic issue?

“Do you think it’s really an issue of the patients being critically ill with vitamin D,” or is it “a chronic issue of having low vitamin D?” asked session moderator Antine Stenbit, MD, PhD, from the University of California, San Diego.

“We don’t know for sure,” Dr. Rice said. Vitamin D might not have a lot of acute effects; it might have effects that are chronic, that work with levels over a period of time, he explained.

“It’s not clear we can correct that with a single dose or with a few days of giving a level that is adequate,” he acknowledged.

Dr. Rice is an investigator in the PETAL network. Dr. Stenbit disclosed no relevant financial relationships.

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

The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.

As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”

To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
 

Limiting trainee exposure

On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”

ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”

New requirements to manage training

The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”

Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”

Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.

“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”

No return to ‘normal’

By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
 

Early graduation, matching, and residencies

On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”

As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”

July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”

On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.

Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
 

New learning formats

The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”

To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”

Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
 

‘We need to keep moving forward’

Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”

Dr. Murano and Dr. Chandra reported having no financial disclosures.

[email protected]

The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.

As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”

To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
 

Limiting trainee exposure

On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”

ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”

New requirements to manage training

The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”

Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”

Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.

“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”

No return to ‘normal’

By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
 

Early graduation, matching, and residencies

On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”

As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”

July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”

On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.

Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
 

New learning formats

The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”

To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”

Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
 

‘We need to keep moving forward’

Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”

Dr. Murano and Dr. Chandra reported having no financial disclosures.

[email protected]

The COVID-19 pandemic has thrown a monkey wrench into the medical education landscape across the entire health care spectrum, disrupting the plans of medical students, residents, fellows, and program directors.

As cases of COVID-19 spread across the United States in early 2020, it became clear to training program directors that immediate action was required to meet the needs of medical learners. The challenges were unlike those surrounding the Ebola virus in 2014, “where we could more easily prevent students and trainees from exposure due to the fact that there were simply not significant numbers of cases in the United States,” Tiffany Murano, MD, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. Dr. Murano is professor of emergency medicine at Rutgers New Jersey Medical School, Newark, and president-elect of the Council of Residency Directors in Emergency Medicine. “COVID was a completely different scenario. We quickly realized that not only was personal protective equipment in short supply, but we also lacked the testing and tracking capabilities for potential exposures. Medical students and other supportive workers who were considered nonessential were removed from the clinical setting. This was after a trial of limiting who the students saw, essentially dampening the risk of exposure. But this proved to be flawed as COVID patients presented with symptoms that were unexpected.”

To complicate matters, she continued, many medical clinics either shut down, had limited access, or converted to telemedicine. Elective surgeries were canceled. This led to an overall pause in clinical medical student rotations and no direct patient care activities. As social distancing mandates were instituted, licensing examination testing centers were closed, and exams and on-campus activities were postponed.
 

Limiting trainee exposure

On the graduate medical education front, some training programs attempted to limit exposure of their trainees to persons under investigation for COVID-19. “As the number of COVID cases grew and encompassed most of what we were seeing in the hospital, it was obvious that residents had to play a vital part in the care of these patients,” said Dr. Murano, who is also a member of the American Council of Graduate Medical Education’s emergency review and recognition committee. “However, there was a consensus among all of the specialties that the procedures that posed the highest risk of exposure would be limited to the most senior or experienced trainees or professionals, and closely supervised by the faculty.”

ACGME activities such as accreditation site visits, clinical environment learning reviews, self-study, and resident and faculty surveys were suspended, postponed, or modified in some way, she said. The ACGME created stages of COVID status to guide sponsoring institutions to suspend learning curricula in order for patients to be cared for. Stage 1 was business as usual, “so there was no significant impact on patient care,” Dr. Murano said. “Stage 2 was increased but manageable clinical demand, while stage 3 was pandemic emergency status, where there were extraordinary circumstances where the clinical demand was so high and strenuous that the routine patient care and education really needed to be reconfigured in order to care for the patients.”

New requirements to manage training

The ACGME also implemented four requirements to manage training that were consistent among institutions, regardless of their COVID stage status. These included making sure that trainees continued to be held to work-hour limit requirements, ensuring adequate resources for training, ensuring that all residents had the appropriate level of supervision at all times, and allowing fellows to function in the core specialty in which they completed their residency training. “This was only possible if the fellows were ABMS [American Board of Medical Specialties] or AOA [American Osteopathic Association] board-eligible, or certified in their core specialty,” Dr. Murano said. “The fellows had to be appointed to the medical staff at the sponsoring institution, and their time spent on the core specialty service would be limited to 20% of their annual education time in any academic year.”

Mindful that there may have been trainees who required a 2-week quarantine period following exposure or potential exposure to COVID-19, some specialty boards showed leniency in residency time required to sit for the written exam. “Testing centers were being forced to close to observe social distancing requirements and heed sanitation recommendations, so exams were either canceled or postponed,” Dr. Murano said. “This posed a special concern for the board certification process, and those specialties with oral examinations had to make a heavy decision regarding whether or not they would allow these exams to take place. Naturally, travel among institutions was suspended or limited, or had quarantine requirements upon returning home from endemic areas. Conferences were either being canceled or converted to virtual formats.”

Subani Chandra, MD, FCCP, of the division of pulmonary, allergy, and critical care medicine at Columbia University, New York, is the internal medicine residency program director and the associate vice-chair of education for the department of medicine, and she recognized the problem created for medical trainees by the changes necessitated by the pandemic.

“The variability in caseloads and clinical exposure has given thrust to the move toward competency-based assessments rather than number- or time-based criteria for determining proficiency and graduation,” she wrote in an email interview. In addition, she noted the impact on medical meetings and the need to adapt. “Early on, before large regional and national conferences adapted to a virtual format, many were canceled altogether. Students, residents, and fellows expecting to have the opportunity to present their scholarly work were suddenly no longer able to do so. Understanding the importance of scholarly interaction, the virtual format of CHEST 2020 is designed with opportunities to present, interact with experts in the field, ask questions, network, and meet mentors.”

No return to ‘normal’

By April 2020, cases in the northeast continued to rise, particularly in the New York, New Jersey, and Connecticut region. “These states were essentially shut down in order to contain spread of the virus,” she said. “This was a real turning point because we realized that things were not going to return to ‘normal’ in the foreseeable future.” With the clinical experience essentially halted for medical students during this time, some medical schools allowed their senior students who met requirements to graduate early. “There were a lot of mixed feelings about this, recognizing that PPE [personal protective equipment] was still in short supply in many areas,” Dr. Murano said. “So, institutions took on these early graduates into roles in which they were not learners in particular, but rather medical workers. They were helping with informatics and technology, telehealth, virtual or telephone call follow-ups, and other tasks like this. There was a movement to virtual learning for the preclinical undergraduate learners, so classes were now online, recorded, or livestreamed.”
 

Early graduation, matching, and residencies

On April 3, the ACGME released a statement regarding graduating students early and appointing them early to the clinical learning environment. “They pointed out that institutions that were in emergency pandemic status lacked the ability to offer the comprehensive orientation and training in PPE and direct supervision required for new residents at the start of their residency,” Dr. Murano said. “Their opinion maintained that graduating medical students matriculate in their previously matched program, the National Resident Match Program start date, or other date that would be nationally determined to be the beginning of the 2020-2021 academic year.”

As May 2020 rolled around, the overriding feeling was uncertainty regarding when, if, and how medical schools were going to open in the early summer and fall. “There was also uncertainty about how graduating medical students were going to function in their new role as residents,” she said. “Same for the graduating residents. There were some who had signed contracts for jobs months before, and had them rescinded, and physicians were being furloughed due to financial hardships that institutions faced. There was also postponement of board certification exams, so people were uncertain about when they would become board certified.”

July 2020 ushered in what Dr. Murano characterized as “a whole new level of stress.” For medical students in particular, “we were entering the application season for residency positions,” she said. “Due to travel restrictions placed by various states and institutions, away rotations were limited or nonexistent. Application release dates through the Electronic Residency Application Service were moved to later in the year. The United States Medical Licensing Examination clinical skills exam was suspended, and there were modifications made for Education Commission for Foreign Medical Graduates requirements. Letters of recommendation were also going to be limited, so there had to be some degree of leniency within specialties to take a more holistic approach to review of applications for residencies.”

On the graduate medical education front, the ACGME sunsetted the initial stages and created two categories: nonemergency, which was formerly stages 1 and 2, and emergency, which was formerly stage 3. “All emergency stages are applied for and granted at 1-month intervals,” Dr. Murano said. Board certification exams were modified to accommodate either later exams or online formats, and specialties with oral examinations faced the task of potentially creating virtual oral exams.

Despite the challenges, Dr. Chandra has seen medical training programs respond with new ideas. “The flexibility and agile adaptability of the entire educational enterprise has been remarkable. The inherent uncertainty in a very dynamic and changing learning environment can be challenging. Recognizing this, many programs are creating additional ways to support the mental, emotional, physical, and financial health of students, residents, and fellows and all health care workers. The importance of this innovative response cannot be overstated.”
 

New learning formats

The pandemic forced Dr. Murano and other medical educators to consider unorthodox learning formats, and virtual learning took center stage. “Residency programs had shared national livestream conferences and grand rounds, and there were virtual curricula made for medical students as well as virtual simulation,” she said. “Telemedicine and telehealth really became important parts of education as well, as this may have been the only face-to-face contact that students and residents had with patients who had non–COVID-related complaints.”

To level the playing field for medical residents during this unprecedented time, a work group of the Coalition for Physician Accountability developed a set of recommendations that include limiting the number of letters of recommendation accepted, limiting the number of away rotations, and allowing alternative or less conventional letters of recommendation. “Keeping an open mind and taking a more holistic approach to applicants has really been needed during this time,” Dr. Murano said. “Virtual interview days have been agreed upon for all specialties. They’re safer, and they allow for students to virtually meet faculty and residents from distant programs that in the past would have been a deterrent due to distance and travel costs. This is not without its own downside, as it’s difficult to determine how well a student will fit into a program without [him or her] actually visiting the institution.”

Dr. Chandra agreed that virtual interviews are necessary but have inherent limitations. However, “we will all learn a lot, and very likely the future process will blend the benefits of both virtual and in-person interviews.”
 

‘We need to keep moving forward’

Dr. Murano concluded her presentation by noting that the COVID-19 pandemic has created opportunities for growth and innovation in medical education, “so we need to keep moving forward. I’ve heard many say that they can’t wait for things to go back to normal. But I think it’s important to go ahead to new and better ways of learning. We’re now thinking outside of the typical education model and are embracing technology and alternative means of education. We don’t know yet if this education is better, worse, or equivalent to traditional methods, but that will be determined and studied in months and years to come, so we’re certainly looking to the future.”

Dr. Murano and Dr. Chandra reported having no financial disclosures.

[email protected]

In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.

“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.

klebercordeiro/Getty Images

She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.

“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.

After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.

Then he asked: “Are you under a lot of stress?”

Throughout the pandemic, people who never had the coronavirus have been reporting a host of seemingly unrelated symptoms: excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.

Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.

Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.

“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.

Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.

Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.

In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).

Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.

Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.

Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.

In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.

Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.

“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
 

How mental stress becomes physical

Stress causes physical changes in the body that can affect nearly every organ system.

Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.

When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.

When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.

Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.

The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).

“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
 

The day-to-day impact

In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.

For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.

He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.

“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.

Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.

Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.

“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
 

How to mitigate chronic stress

When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.

That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:

• Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
• Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
• Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
• Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.

“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.

“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.

klebercordeiro/Getty Images

She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.

“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.

After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.

Then he asked: “Are you under a lot of stress?”

Throughout the pandemic, people who never had the coronavirus have been reporting a host of seemingly unrelated symptoms: excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.

Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.

Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.

“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.

Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.

Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.

In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).

Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.

Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.

Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.

In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.

Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.

“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
 

How mental stress becomes physical

Stress causes physical changes in the body that can affect nearly every organ system.

Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.

When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.

When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.

Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.

The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).

“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
 

The day-to-day impact

In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.

For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.

He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.

“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.

Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.

Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.

“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
 

How to mitigate chronic stress

When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.

That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:

• Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
• Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
• Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
• Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.

“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.

“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.

klebercordeiro/Getty Images

She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.

“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.

After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.

Then he asked: “Are you under a lot of stress?”

Throughout the pandemic, people who never had the coronavirus have been reporting a host of seemingly unrelated symptoms: excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.

Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.

Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.

“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.

Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.

Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.

In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).

Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.

Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.

Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.

In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.

Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.

“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
 

How mental stress becomes physical

Stress causes physical changes in the body that can affect nearly every organ system.

Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.

When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.

When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.

Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.

The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).

“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
 

The day-to-day impact

In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.

For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.

He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.

“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.

Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.

Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.

“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
 

How to mitigate chronic stress

When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.

That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:

• Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
• Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
• Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
• Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.

“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A recent Medscape survey found there were high levels of loneliness, stress, and burnout in physicians during the COVID-19 pandemic. Isolation and relationship stress add to the problem.

Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.

As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.

Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.

“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”

Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
 

Physicians feel a sense of betrayal

Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.

“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.

Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.

Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.

The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
 

Not what they signed up for

Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)

Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.

“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.

The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.

David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.

“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.

Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
 

New situations create more anxiety

Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.

Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
 

Relationships became more challenging

Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.

One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”

Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”

On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”

As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.

Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.

Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”

Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.

“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
 

Socializing outside the box

Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.

Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.

“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”

Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.

Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
 

The importance of ‘fixing’ the workplace

Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.

At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.

Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.

Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.

Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”

Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”

For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.

This article first appeared on Medscape.com.

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.