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Risk for severe COVID-19 and death plummets with Pfizer booster
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
CLL and COVID-19: Outcome trends and lessons learned
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
FROM BLOOD
Intent to vaccinate kids against COVID higher among vaccinated parents
“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.
The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.
Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.
The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.
The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.
Hesitance in vaccinated parents
Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.
“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.
In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”
Advice for clinicians from outside expert
“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.
Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.
“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.
The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.
Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.
The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.
The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.
Hesitance in vaccinated parents
Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.
“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.
In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”
Advice for clinicians from outside expert
“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.
Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.
“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.
The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.
Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.
The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.
The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.
Hesitance in vaccinated parents
Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.
“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.
In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”
Advice for clinicians from outside expert
“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.
Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.
FROM JAMA PEDIATRICS
Clinical Edge Journal Scan Commentary: COVID-19 December 2021
A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.
Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77), the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.
A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.
Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77), the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.
A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.
Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77), the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.
It feels like COVID is closing in
Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.
In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.
In the beginning, I awoke with rising anxiety every morning at 4 a.m.
Now, it is part of life. We know how to do this.
I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.
I felt lucky.
Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.
We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.
Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.
I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.
I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?
Of course, I am vaccinated with a booster shot. But breakthrough infections occur.
I am lucky, I keep reminding myself. I have a job and income and good PPE.
So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”
“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.
All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.
All appointments are mainly telehealth. That has its pros and cons.
So bottom line – I will keep keeping on.
But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic?
Here are a few suggestions, some of which I have made before:
- Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
- Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
- Talk through established media about self-care and therapy for anxiety and depression.
- Clean out your closets. Give clothes to Afghan refugees.
- Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
- Take care of veterans and the elderly and homeless.
- Take care of yourself and your family.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.
Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.
In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.
In the beginning, I awoke with rising anxiety every morning at 4 a.m.
Now, it is part of life. We know how to do this.
I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.
I felt lucky.
Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.
We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.
Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.
I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.
I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?
Of course, I am vaccinated with a booster shot. But breakthrough infections occur.
I am lucky, I keep reminding myself. I have a job and income and good PPE.
So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”
“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.
All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.
All appointments are mainly telehealth. That has its pros and cons.
So bottom line – I will keep keeping on.
But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic?
Here are a few suggestions, some of which I have made before:
- Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
- Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
- Talk through established media about self-care and therapy for anxiety and depression.
- Clean out your closets. Give clothes to Afghan refugees.
- Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
- Take care of veterans and the elderly and homeless.
- Take care of yourself and your family.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.
Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.
In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.
In the beginning, I awoke with rising anxiety every morning at 4 a.m.
Now, it is part of life. We know how to do this.
I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.
I felt lucky.
Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.
We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.
Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.
I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.
I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?
Of course, I am vaccinated with a booster shot. But breakthrough infections occur.
I am lucky, I keep reminding myself. I have a job and income and good PPE.
So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”
“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.
All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.
All appointments are mainly telehealth. That has its pros and cons.
So bottom line – I will keep keeping on.
But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic?
Here are a few suggestions, some of which I have made before:
- Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
- Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
- Talk through established media about self-care and therapy for anxiety and depression.
- Clean out your closets. Give clothes to Afghan refugees.
- Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
- Take care of veterans and the elderly and homeless.
- Take care of yourself and your family.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.
CDC unveils mental health protection plan for health care workers
Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.
“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.
“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
Burnout is not selective
There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.
He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.
Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.
Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. , Dr. Howard said.
Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data.
“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.
Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.
“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
Primary prevention approach
To tackle the burnout crisis, NIOSH plans to:
- Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
- Assimilate the evidence and create a repository of best practices, resources, and interventions.
- Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
- Identify and adapt tools for the health care workplace that emphasize stress reduction.
NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.
This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.
Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.
A version of this article first appeared on Medscape.com.
Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.
“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.
“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
Burnout is not selective
There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.
He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.
Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.
Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. , Dr. Howard said.
Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data.
“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.
Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.
“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
Primary prevention approach
To tackle the burnout crisis, NIOSH plans to:
- Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
- Assimilate the evidence and create a repository of best practices, resources, and interventions.
- Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
- Identify and adapt tools for the health care workplace that emphasize stress reduction.
NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.
This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.
Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.
A version of this article first appeared on Medscape.com.
Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.
“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.
“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
Burnout is not selective
There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.
He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.
Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.
Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. , Dr. Howard said.
Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data.
“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.
Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.
“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
Primary prevention approach
To tackle the burnout crisis, NIOSH plans to:
- Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
- Assimilate the evidence and create a repository of best practices, resources, and interventions.
- Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
- Identify and adapt tools for the health care workplace that emphasize stress reduction.
NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.
This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.
Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.
A version of this article first appeared on Medscape.com.
More tools for the COVID toolbox
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
High-dose fish oil: ‘Intriguing’ results in COVID-19
A high dose of the purified form of eicosapentaenoic acid, icosapent ethyl (Vascepa, Amarin), failed to significantly reduce hospitalizations or death in patients infected with COVID-19 in the PREPARE-IT 2 study.
The study did, however, show a favorable trend, with a 16% reduction in the primary endpoint of death or an indication for hospitalization. All secondary endpoints were also numerically reduced, but none reached statistical significance.
The product was also well tolerated over the 28 days of the study period, even though a new high-loading dose was used, with no increase in atrial fibrillation or bleeding or other adverse events versus placebo, although there was a slightly higher rate of discontinuation.
The trial was presented at the American Heart Association scientific sessions on Nov. 15 by Rafael Díaz, MD, director of Estudios Clínicos Latinoamérica in Rosario, Argentina.
“Larger, randomized trials powered for a relative risk reduction of around 15% with icosapent ethyl are needed to establish whether or not this product may have a role in the management of COVID-positive outpatients,” Dr. Diaz concluded.
‘Intriguing signals’
Commenting on the study, Manesh Patel, MD, chief of the division of cardiology and codirector of the Heart Center at Duke University, Durham, N.C., and chair of the Scientific Sessions scientific program, said that: “Certainly there are some intriguing signals.”
“I think the trend is valuable, but do we need a larger trial to confirm a benefit? I will leave that to the clinical community to decide,” Dr. Patel added. “But it is hard to power a trial to get that answer, and the world of COVID has changed since this trial started with vaccines now available and new therapeutics coming. So, there’s going to be a competing landscape.”
Discussing the trial at an AHA news briefing, Erin Michos, MD, associate professor of medicine within the division of cardiology at Johns Hopkins University, Baltimore, said: “Results showed that everything trended in the right direction, but did not reach statistical significance largely because there were fewer events than anticipated. COVID hospitalizations are going down because of the broad adoption of vaccines, which meant that this study didn’t quite meet its endpoint.”
But, she added: “Reassuringly, even with the higher loading dose, there was no increased risk of [atrial fibrillation] when used for just 28 days, and no increased risk in bleeding, so there was very good safety.”
“We need a larger trial to really definitely show whether icosapent ethyl can or cannot help COVID-positive outpatients, but I think a better prevention strategy would be the broad adoption of vaccinations globally,” Dr. Michos concluded.
‘A pretty big ask’
Donald Lloyd-Jones, MD, AHA president and designated discussant at the late-breaking science session, congratulated the investigators on conducting “a very nice pragmatic trial in the midst of the COVID pandemic.”
Dr. Lloyd-Jones concluded that the broad range of potentially beneficial actions of icosapent ethyl – including antitriglyceride, anti-inflammatory, antioxidant, and antithrombotic effects – leads to the possibility of it helping in COVID, but he added that “this is a pretty big ask for a fish oil supplement given short term.”
Presenting the study, Dr. Diaz noted that there are limited options for the outpatient treatment of patients with COVID-19 infection, and it is believed that inflammation plays a major role in worsening the severity of the infection.
He pointed out that previous data support a potential role of omega-3 fatty acids in reducing inflammation and infection, and that icosapent ethyl has shown a reduction in major cardiovascular events in the REDUCE-IT trial, with the mechanism thought to involve anti-inflammatory effects.
In the first trial to investigate the role of icosapent ethyl in COVID-19, PREPARE-IT, the product did not prevent uninfected individuals at risk from COVID from becoming infected with the virus, but there was no increase in side effects versus placebo with use over a 60-day period.
A small study last year in 100 COVID-positive patients showed icosapent ethyl reduced C-reactive protein, an inflammatory marker, and also improved symptoms.
PREPARE-IT 2, a pragmatic web-based trial, was conducted to investigate whether icosapent ethyl in nonhospitalized patients with a positive diagnosis of COVID-19 could reduce hospitalization rates and complications.
The trial enrolled 2,052 patients (mean age, 50 years), of whom 1,010 were allocated to the active group and 1,042 to the placebo group. Inclusion criteria included individuals aged 40 years or older with a confirmed COVID-19 diagnosis and no more than 7 days from the onset of symptoms and without a clear indication for hospitalization.
Patients who were allocated to the active arm received icosapent ethyl at a dose of 8 g (four capsules every 12 hours, morning and evening) for the first 3 days, followed by 4 g (two capsules every 12 hours) thereafter (days 4-28).
The primary outcome, COVID-19–related hospitalization (indication for hospitalization or hospitalization) or death at 28 days, occurred in 11.16% of the active group and 13.69% of the placebo group, giving a hazard ratio of 0.84 (95% confidence interval, 0.65-1.08; P = .166)
Secondary outcomes showed similar positive trends, but none were significant. These included: death or still hospitalized at 28 days (HR, 0.74), major events (MI, stroke, death; HR, 0.38), and total mortality (HR, 0.52).
In terms of safety, there was no significant difference in total adverse events between the two groups (16.5% in the active group vs. 14.8% in the placebo group). The most common adverse effects were constipation (2.7%), diarrhea (7.2%), and nausea (4%), but these were not significantly different from placebo. There were, however, more discontinuations in the active group (7% vs. 4%).
Dr. Diaz pointed out that the PREPARE-IT 2 trial was started in May 2020, when there wasn’t much known about the COVID-19 condition, and there were no vaccines or treatments, so hospitalization rates were high.
“We were hoping to see a 25%-30% reduction in hospitalizations with icosapent ethyl, and the trial was powered for that sort of reduction, but today we know we can expect a more modest reduction of about 15%,” Dr. Diaz concluded. “But to show that, we need a much larger trial with 8,000 or 9,000 patients, and that will be much more difficult to conduct.”
The PREPARE-IT 2 study was funded by Amarin. Dr. Diaz has received grants from Dalcor, Amarin, PHRI, and Lepetit.
A version of this article first appeared on Medscape.com.
A high dose of the purified form of eicosapentaenoic acid, icosapent ethyl (Vascepa, Amarin), failed to significantly reduce hospitalizations or death in patients infected with COVID-19 in the PREPARE-IT 2 study.
The study did, however, show a favorable trend, with a 16% reduction in the primary endpoint of death or an indication for hospitalization. All secondary endpoints were also numerically reduced, but none reached statistical significance.
The product was also well tolerated over the 28 days of the study period, even though a new high-loading dose was used, with no increase in atrial fibrillation or bleeding or other adverse events versus placebo, although there was a slightly higher rate of discontinuation.
The trial was presented at the American Heart Association scientific sessions on Nov. 15 by Rafael Díaz, MD, director of Estudios Clínicos Latinoamérica in Rosario, Argentina.
“Larger, randomized trials powered for a relative risk reduction of around 15% with icosapent ethyl are needed to establish whether or not this product may have a role in the management of COVID-positive outpatients,” Dr. Diaz concluded.
‘Intriguing signals’
Commenting on the study, Manesh Patel, MD, chief of the division of cardiology and codirector of the Heart Center at Duke University, Durham, N.C., and chair of the Scientific Sessions scientific program, said that: “Certainly there are some intriguing signals.”
“I think the trend is valuable, but do we need a larger trial to confirm a benefit? I will leave that to the clinical community to decide,” Dr. Patel added. “But it is hard to power a trial to get that answer, and the world of COVID has changed since this trial started with vaccines now available and new therapeutics coming. So, there’s going to be a competing landscape.”
Discussing the trial at an AHA news briefing, Erin Michos, MD, associate professor of medicine within the division of cardiology at Johns Hopkins University, Baltimore, said: “Results showed that everything trended in the right direction, but did not reach statistical significance largely because there were fewer events than anticipated. COVID hospitalizations are going down because of the broad adoption of vaccines, which meant that this study didn’t quite meet its endpoint.”
But, she added: “Reassuringly, even with the higher loading dose, there was no increased risk of [atrial fibrillation] when used for just 28 days, and no increased risk in bleeding, so there was very good safety.”
“We need a larger trial to really definitely show whether icosapent ethyl can or cannot help COVID-positive outpatients, but I think a better prevention strategy would be the broad adoption of vaccinations globally,” Dr. Michos concluded.
‘A pretty big ask’
Donald Lloyd-Jones, MD, AHA president and designated discussant at the late-breaking science session, congratulated the investigators on conducting “a very nice pragmatic trial in the midst of the COVID pandemic.”
Dr. Lloyd-Jones concluded that the broad range of potentially beneficial actions of icosapent ethyl – including antitriglyceride, anti-inflammatory, antioxidant, and antithrombotic effects – leads to the possibility of it helping in COVID, but he added that “this is a pretty big ask for a fish oil supplement given short term.”
Presenting the study, Dr. Diaz noted that there are limited options for the outpatient treatment of patients with COVID-19 infection, and it is believed that inflammation plays a major role in worsening the severity of the infection.
He pointed out that previous data support a potential role of omega-3 fatty acids in reducing inflammation and infection, and that icosapent ethyl has shown a reduction in major cardiovascular events in the REDUCE-IT trial, with the mechanism thought to involve anti-inflammatory effects.
In the first trial to investigate the role of icosapent ethyl in COVID-19, PREPARE-IT, the product did not prevent uninfected individuals at risk from COVID from becoming infected with the virus, but there was no increase in side effects versus placebo with use over a 60-day period.
A small study last year in 100 COVID-positive patients showed icosapent ethyl reduced C-reactive protein, an inflammatory marker, and also improved symptoms.
PREPARE-IT 2, a pragmatic web-based trial, was conducted to investigate whether icosapent ethyl in nonhospitalized patients with a positive diagnosis of COVID-19 could reduce hospitalization rates and complications.
The trial enrolled 2,052 patients (mean age, 50 years), of whom 1,010 were allocated to the active group and 1,042 to the placebo group. Inclusion criteria included individuals aged 40 years or older with a confirmed COVID-19 diagnosis and no more than 7 days from the onset of symptoms and without a clear indication for hospitalization.
Patients who were allocated to the active arm received icosapent ethyl at a dose of 8 g (four capsules every 12 hours, morning and evening) for the first 3 days, followed by 4 g (two capsules every 12 hours) thereafter (days 4-28).
The primary outcome, COVID-19–related hospitalization (indication for hospitalization or hospitalization) or death at 28 days, occurred in 11.16% of the active group and 13.69% of the placebo group, giving a hazard ratio of 0.84 (95% confidence interval, 0.65-1.08; P = .166)
Secondary outcomes showed similar positive trends, but none were significant. These included: death or still hospitalized at 28 days (HR, 0.74), major events (MI, stroke, death; HR, 0.38), and total mortality (HR, 0.52).
In terms of safety, there was no significant difference in total adverse events between the two groups (16.5% in the active group vs. 14.8% in the placebo group). The most common adverse effects were constipation (2.7%), diarrhea (7.2%), and nausea (4%), but these were not significantly different from placebo. There were, however, more discontinuations in the active group (7% vs. 4%).
Dr. Diaz pointed out that the PREPARE-IT 2 trial was started in May 2020, when there wasn’t much known about the COVID-19 condition, and there were no vaccines or treatments, so hospitalization rates were high.
“We were hoping to see a 25%-30% reduction in hospitalizations with icosapent ethyl, and the trial was powered for that sort of reduction, but today we know we can expect a more modest reduction of about 15%,” Dr. Diaz concluded. “But to show that, we need a much larger trial with 8,000 or 9,000 patients, and that will be much more difficult to conduct.”
The PREPARE-IT 2 study was funded by Amarin. Dr. Diaz has received grants from Dalcor, Amarin, PHRI, and Lepetit.
A version of this article first appeared on Medscape.com.
A high dose of the purified form of eicosapentaenoic acid, icosapent ethyl (Vascepa, Amarin), failed to significantly reduce hospitalizations or death in patients infected with COVID-19 in the PREPARE-IT 2 study.
The study did, however, show a favorable trend, with a 16% reduction in the primary endpoint of death or an indication for hospitalization. All secondary endpoints were also numerically reduced, but none reached statistical significance.
The product was also well tolerated over the 28 days of the study period, even though a new high-loading dose was used, with no increase in atrial fibrillation or bleeding or other adverse events versus placebo, although there was a slightly higher rate of discontinuation.
The trial was presented at the American Heart Association scientific sessions on Nov. 15 by Rafael Díaz, MD, director of Estudios Clínicos Latinoamérica in Rosario, Argentina.
“Larger, randomized trials powered for a relative risk reduction of around 15% with icosapent ethyl are needed to establish whether or not this product may have a role in the management of COVID-positive outpatients,” Dr. Diaz concluded.
‘Intriguing signals’
Commenting on the study, Manesh Patel, MD, chief of the division of cardiology and codirector of the Heart Center at Duke University, Durham, N.C., and chair of the Scientific Sessions scientific program, said that: “Certainly there are some intriguing signals.”
“I think the trend is valuable, but do we need a larger trial to confirm a benefit? I will leave that to the clinical community to decide,” Dr. Patel added. “But it is hard to power a trial to get that answer, and the world of COVID has changed since this trial started with vaccines now available and new therapeutics coming. So, there’s going to be a competing landscape.”
Discussing the trial at an AHA news briefing, Erin Michos, MD, associate professor of medicine within the division of cardiology at Johns Hopkins University, Baltimore, said: “Results showed that everything trended in the right direction, but did not reach statistical significance largely because there were fewer events than anticipated. COVID hospitalizations are going down because of the broad adoption of vaccines, which meant that this study didn’t quite meet its endpoint.”
But, she added: “Reassuringly, even with the higher loading dose, there was no increased risk of [atrial fibrillation] when used for just 28 days, and no increased risk in bleeding, so there was very good safety.”
“We need a larger trial to really definitely show whether icosapent ethyl can or cannot help COVID-positive outpatients, but I think a better prevention strategy would be the broad adoption of vaccinations globally,” Dr. Michos concluded.
‘A pretty big ask’
Donald Lloyd-Jones, MD, AHA president and designated discussant at the late-breaking science session, congratulated the investigators on conducting “a very nice pragmatic trial in the midst of the COVID pandemic.”
Dr. Lloyd-Jones concluded that the broad range of potentially beneficial actions of icosapent ethyl – including antitriglyceride, anti-inflammatory, antioxidant, and antithrombotic effects – leads to the possibility of it helping in COVID, but he added that “this is a pretty big ask for a fish oil supplement given short term.”
Presenting the study, Dr. Diaz noted that there are limited options for the outpatient treatment of patients with COVID-19 infection, and it is believed that inflammation plays a major role in worsening the severity of the infection.
He pointed out that previous data support a potential role of omega-3 fatty acids in reducing inflammation and infection, and that icosapent ethyl has shown a reduction in major cardiovascular events in the REDUCE-IT trial, with the mechanism thought to involve anti-inflammatory effects.
In the first trial to investigate the role of icosapent ethyl in COVID-19, PREPARE-IT, the product did not prevent uninfected individuals at risk from COVID from becoming infected with the virus, but there was no increase in side effects versus placebo with use over a 60-day period.
A small study last year in 100 COVID-positive patients showed icosapent ethyl reduced C-reactive protein, an inflammatory marker, and also improved symptoms.
PREPARE-IT 2, a pragmatic web-based trial, was conducted to investigate whether icosapent ethyl in nonhospitalized patients with a positive diagnosis of COVID-19 could reduce hospitalization rates and complications.
The trial enrolled 2,052 patients (mean age, 50 years), of whom 1,010 were allocated to the active group and 1,042 to the placebo group. Inclusion criteria included individuals aged 40 years or older with a confirmed COVID-19 diagnosis and no more than 7 days from the onset of symptoms and without a clear indication for hospitalization.
Patients who were allocated to the active arm received icosapent ethyl at a dose of 8 g (four capsules every 12 hours, morning and evening) for the first 3 days, followed by 4 g (two capsules every 12 hours) thereafter (days 4-28).
The primary outcome, COVID-19–related hospitalization (indication for hospitalization or hospitalization) or death at 28 days, occurred in 11.16% of the active group and 13.69% of the placebo group, giving a hazard ratio of 0.84 (95% confidence interval, 0.65-1.08; P = .166)
Secondary outcomes showed similar positive trends, but none were significant. These included: death or still hospitalized at 28 days (HR, 0.74), major events (MI, stroke, death; HR, 0.38), and total mortality (HR, 0.52).
In terms of safety, there was no significant difference in total adverse events between the two groups (16.5% in the active group vs. 14.8% in the placebo group). The most common adverse effects were constipation (2.7%), diarrhea (7.2%), and nausea (4%), but these were not significantly different from placebo. There were, however, more discontinuations in the active group (7% vs. 4%).
Dr. Diaz pointed out that the PREPARE-IT 2 trial was started in May 2020, when there wasn’t much known about the COVID-19 condition, and there were no vaccines or treatments, so hospitalization rates were high.
“We were hoping to see a 25%-30% reduction in hospitalizations with icosapent ethyl, and the trial was powered for that sort of reduction, but today we know we can expect a more modest reduction of about 15%,” Dr. Diaz concluded. “But to show that, we need a much larger trial with 8,000 or 9,000 patients, and that will be much more difficult to conduct.”
The PREPARE-IT 2 study was funded by Amarin. Dr. Diaz has received grants from Dalcor, Amarin, PHRI, and Lepetit.
A version of this article first appeared on Medscape.com.
FROM AHA 2021
The Sobering Medical, Emotional, Psychological Challenge of Covid-19
Cheryl K. Lee, MD, an Assistant Professor of Medicine at Northwestern Feinberg School of Medicine, practices internal medicine and pediatrics at Northwestern Memorial and the Ann & Robert H. Lurie Children's Hospital, both in Chicago, IL. She also serves on the Northwestern Medicine Covid Quality Committee and as core clinical faculty in the Internal Medicine Residency.
Is it fair to say that for hospitalists, the pandemic has been a sobering experience, why so?
Dr. Lee: There are several reasons; one stems from the increasing impact of Covid on children. Early in the pandemic, young children, teens, and young adults were not infected or hospitalized at the rate of older adults.1 For those of us who care for hospitalized patients, that early finding was somewhat of a relief, knowing at least one portion of the population wasn’t as heavily affected. In fact, I normally split my time as a pediatric and adult hospitalist, and I was reassigned to work full-time in the adult hospital because so few children had been admitted. But all that changed with the arrival of the highly transmissible Delta variant and the loosening of social distancing and masking guidelines and other regulations. The American Academy of Pediatrics2 reported that, as of October, 8,364 of every 100,000 children have been infected by Covid, largely driven by the summer surge. Furthermore, pediatric Covid hospitalizations increased five-fold in August 2021 as compared to the prior 6 weeks. And these numbers likely underestimate the true impact, as several states did not release complete reports and did not account for long-term sequelae from milder infections.
What other issues were far-reaching for hospitalists?
Dr. Lee: Early in 2020, we were scrambling to learn about a novel, deadly, highly transmissible disease. Some groups in our population were experiencing a high fatality rate, and the medical community had no proven treatments. We felt helpless in caring for these patients who pleaded for our help and ultimately died. When data proved that medications like steroids were effective and the vaccines arrived, I had hoped that the pandemic would be ending. But now with the quick dissemination of false information and the evolution of new variants, we are left caring for seriously ill, unvaccinated patients along with younger patients. The heartbreaking thing is that these are largely preventable tragedies now that we have effective vaccines.
What medications have changed the course of Covid in the hospital?
Dr. Lee: Steroids are interesting; they are a good reminder that Covid has different stages and that we should be mindful of how we treat patients within those particular stages. Simply, Covid infection begins with a phase of viral replication characterized by fevers, cough, loss of taste and smell, and gastrointestinal symptoms. In time, this is followed by a second phase of high inflammation and immune response, sometimes causing hypoxemia and respiratory failure. What we know is that steroids such as dexamethasone reduce mortality, but they are only effective during this second phase, and only in those whose oxygen levels are low enough to require oxygen. This was not an intuitive finding, since steroids do not help, and may harm, those with other viral pneumonias, such as influenza. Steroid use in severe, hypoxemic Covid, however, is life-saving and the mainstay of inpatient care which might include antivirals and interleukin-6 inhibitors3 in select patients. As with steroid use in other patients, physicians should watch their Covid patients for hyperglycemia4 and delirium. That said, steroids provide a mortality benefit that strongly supports their continued use -- in tandem with management of those expected side effects. Last, it is important to note that steroid use has been associated with possible harm when given to those with mild Covid,5 so its use should be avoided, in light of its expected side effects, unless a patient requires supplemental oxygen.
That said, although steroids can be helpful for our sickest patients, vaccines are the best medicine of all because they can allow patients to avoid hospitalization and death -- outcomes that far outweigh what steroids or any other medication can do for the gravely ill.
Given the complexity of the evidence surrounding the treatments for Covid in the hospital, no wonder some people are confused about which medicines work.
Dr. Lee: First, let me say that I have yet to encounter a patient or family member whose motivation to ask questions or question a loved one’s treatment wasn’t grounded in concern and fear for their loved one.
What do they ask about?
Dr. Lee: They ask about alternative treatments, anti-parasitics, even vitamins. I agree with them that there is so much out there about Covid that it is difficult for anyone to know what is true or false. I then explain what therapies are proven – medications such as steroids and supportive care such as oxygen and prone positioning. I also review the lack of good evidence for the alternative treatments that they ask about. It is sometimes surprising to folks that all research isn’t conducted with equal rigor, and that false conclusions can be made based on faulty evidence. A good example is how providers used hydroxychloroquine early in the pandemic, but ultimately it didn’t prove to be helpful. Although we are always hopeful and looking for new therapies, I say, those specific alternatives haven’t worked out. And I end with a promise that I will continue to keep up with the literature and let them know when something new does look promising.
Your responses to the above questions prompts this one: How do physicians who are treating Covid-19 stay on top of what is being learned about Covid-19? At last count, there were 191,968 results in PubMed, found using that sole keyword.
Dr. Lee: One of the amazing things about the Covid era is that members of the scientific community dropped everything to research Covid. But on the flip side, there is now a lot of research out there, and it frankly has become difficult to keep up with it. Our hospital system identified a core group of collaborators with backgrounds such as pharmacy, nursing, infectious disease, pulmonary, and hospital medicine to regularly review the evidence and identify anything that has strong enough evidence to change our system’s clinical practice. Furthermore, I regularly tap consultants in various specialties to help me contextualize new research. And I’ve found it helpful to review the living practice guidelines from the Infectious Disease Society of America and the NIH.3,6
What else has been remarkable about the last 19 months?
Dr. Lee: I have never spent this much time talking with patients and their caregivers. I’ve always been one to talk a lot with families, but it feels like the pandemic has created another level. My guess is that many colleagues are experiencing the same thing. Caring for hospitalized Covid patients is not only intense from a medical standpoint, but also from a psychosocial vantage point. Patients are ill and usually scared, and they are supported by friends and family who are equally afraid for them, who furthermore can’t visit because of isolation needs. And I often forget that, besides Covid, families have gone through immense social and financial changes. Sometimes communication can be fraught because of that stress. I am trying to be mindful that patients and families come into the hospital with a lot of these burdens, so that, if the conversation takes a tense turn, I will try not to take it personally. Some days are harder than others.
What you are describing isn’t necessarily an innate skill.
Dr. Lee: Absolutely. As have many others, our medical school and residency program has been incorporating communication skills into the standard curriculum, analogous to teaching anatomy or heart failure treatments. We are more aware that handling a difficult conversation isn’t an instinctive thing; that it must be modeled and learned. But I was surprised at how communication in a pandemic, when caretakers can’t see their loved ones, is truly a unique challenge. It is challenging for me despite being in practice for several years.
What will happen when the pandemic subsides? How much of the impact of Covid will stay with you, when dealing with a broken leg, or a patient with osteoporosis?
Dr. Lee: There will be lasting effects of this era on the health-care workforce, but I honestly can’t predict how severe that impact will be or how long-lasting. Already we are seeing health-care workers drop out of the workforce, driven by effects of the pandemic itself, increased workload, or being underpaid.7 This is occurring alongside a national conversation that cannot agree on life-saving interventions such as vaccines. I worry that the current environment will lead to many more dropping out.
What can hospital administrators do now to put stop gaps in place? What advice would you give to them?
Dr. Lee: Workers in each hospital will have unique needs and stressors, so it makes sense that the first step is to provide an opportunity to make their opinions heard. It may be tempting for hospitals to jump on quick fixes such as offering classes in “resilience training,” but that may not be a data-driven solution, particularly if burnout is being driven by an ever increasing workload.
References
- L. Shekerdemian, N. Mahmood, K.Wolfe, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (Covid-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020 Sep; 174(9): 1–6.
- Children and Covid-19: State-Level Data Report. American Academy of Pediatrics. Published Oct. 25, 2021. https://www.aap.org/en/pages/2019-novel-coronavirus-Covid-19-infections/children-and-Covid-19-state-level-data-report/
- NIH. Therapeutic Management of Hospitalized Adults with Covid-19. Last updated August 25, 2021. https://www.Covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/
- Sosale A, Sosale B, Kesavadev J, et al. Steroid use during Covid-19 infection and hyperglycemia - What a physician should know. Diabetes Metab Syndr. 2021;15(4):102167. doi:10.1016/j.dsx.2021.06.004
- The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693-704.
- IDSA. IDSA Guidelines on the Treatment and Management of Patients with Covid-19. Last updated November 1, 2021. https://www.idsociety.org/practice-guideline/Covid-19-guideline-treatment-and-management/
- Galvin, G. “Nearly 1 in 5 Health Care Workers Have Quit Their Jobs During the Pandemic.” Morning Consult. https://morningconsult.com/2021/10/04/health-care-workers-series-part-2-workforce/ Accessed November 1, 2021.
Cheryl K. Lee, MD, an Assistant Professor of Medicine at Northwestern Feinberg School of Medicine, practices internal medicine and pediatrics at Northwestern Memorial and the Ann & Robert H. Lurie Children's Hospital, both in Chicago, IL. She also serves on the Northwestern Medicine Covid Quality Committee and as core clinical faculty in the Internal Medicine Residency.
Is it fair to say that for hospitalists, the pandemic has been a sobering experience, why so?
Dr. Lee: There are several reasons; one stems from the increasing impact of Covid on children. Early in the pandemic, young children, teens, and young adults were not infected or hospitalized at the rate of older adults.1 For those of us who care for hospitalized patients, that early finding was somewhat of a relief, knowing at least one portion of the population wasn’t as heavily affected. In fact, I normally split my time as a pediatric and adult hospitalist, and I was reassigned to work full-time in the adult hospital because so few children had been admitted. But all that changed with the arrival of the highly transmissible Delta variant and the loosening of social distancing and masking guidelines and other regulations. The American Academy of Pediatrics2 reported that, as of October, 8,364 of every 100,000 children have been infected by Covid, largely driven by the summer surge. Furthermore, pediatric Covid hospitalizations increased five-fold in August 2021 as compared to the prior 6 weeks. And these numbers likely underestimate the true impact, as several states did not release complete reports and did not account for long-term sequelae from milder infections.
What other issues were far-reaching for hospitalists?
Dr. Lee: Early in 2020, we were scrambling to learn about a novel, deadly, highly transmissible disease. Some groups in our population were experiencing a high fatality rate, and the medical community had no proven treatments. We felt helpless in caring for these patients who pleaded for our help and ultimately died. When data proved that medications like steroids were effective and the vaccines arrived, I had hoped that the pandemic would be ending. But now with the quick dissemination of false information and the evolution of new variants, we are left caring for seriously ill, unvaccinated patients along with younger patients. The heartbreaking thing is that these are largely preventable tragedies now that we have effective vaccines.
What medications have changed the course of Covid in the hospital?
Dr. Lee: Steroids are interesting; they are a good reminder that Covid has different stages and that we should be mindful of how we treat patients within those particular stages. Simply, Covid infection begins with a phase of viral replication characterized by fevers, cough, loss of taste and smell, and gastrointestinal symptoms. In time, this is followed by a second phase of high inflammation and immune response, sometimes causing hypoxemia and respiratory failure. What we know is that steroids such as dexamethasone reduce mortality, but they are only effective during this second phase, and only in those whose oxygen levels are low enough to require oxygen. This was not an intuitive finding, since steroids do not help, and may harm, those with other viral pneumonias, such as influenza. Steroid use in severe, hypoxemic Covid, however, is life-saving and the mainstay of inpatient care which might include antivirals and interleukin-6 inhibitors3 in select patients. As with steroid use in other patients, physicians should watch their Covid patients for hyperglycemia4 and delirium. That said, steroids provide a mortality benefit that strongly supports their continued use -- in tandem with management of those expected side effects. Last, it is important to note that steroid use has been associated with possible harm when given to those with mild Covid,5 so its use should be avoided, in light of its expected side effects, unless a patient requires supplemental oxygen.
That said, although steroids can be helpful for our sickest patients, vaccines are the best medicine of all because they can allow patients to avoid hospitalization and death -- outcomes that far outweigh what steroids or any other medication can do for the gravely ill.
Given the complexity of the evidence surrounding the treatments for Covid in the hospital, no wonder some people are confused about which medicines work.
Dr. Lee: First, let me say that I have yet to encounter a patient or family member whose motivation to ask questions or question a loved one’s treatment wasn’t grounded in concern and fear for their loved one.
What do they ask about?
Dr. Lee: They ask about alternative treatments, anti-parasitics, even vitamins. I agree with them that there is so much out there about Covid that it is difficult for anyone to know what is true or false. I then explain what therapies are proven – medications such as steroids and supportive care such as oxygen and prone positioning. I also review the lack of good evidence for the alternative treatments that they ask about. It is sometimes surprising to folks that all research isn’t conducted with equal rigor, and that false conclusions can be made based on faulty evidence. A good example is how providers used hydroxychloroquine early in the pandemic, but ultimately it didn’t prove to be helpful. Although we are always hopeful and looking for new therapies, I say, those specific alternatives haven’t worked out. And I end with a promise that I will continue to keep up with the literature and let them know when something new does look promising.
Your responses to the above questions prompts this one: How do physicians who are treating Covid-19 stay on top of what is being learned about Covid-19? At last count, there were 191,968 results in PubMed, found using that sole keyword.
Dr. Lee: One of the amazing things about the Covid era is that members of the scientific community dropped everything to research Covid. But on the flip side, there is now a lot of research out there, and it frankly has become difficult to keep up with it. Our hospital system identified a core group of collaborators with backgrounds such as pharmacy, nursing, infectious disease, pulmonary, and hospital medicine to regularly review the evidence and identify anything that has strong enough evidence to change our system’s clinical practice. Furthermore, I regularly tap consultants in various specialties to help me contextualize new research. And I’ve found it helpful to review the living practice guidelines from the Infectious Disease Society of America and the NIH.3,6
What else has been remarkable about the last 19 months?
Dr. Lee: I have never spent this much time talking with patients and their caregivers. I’ve always been one to talk a lot with families, but it feels like the pandemic has created another level. My guess is that many colleagues are experiencing the same thing. Caring for hospitalized Covid patients is not only intense from a medical standpoint, but also from a psychosocial vantage point. Patients are ill and usually scared, and they are supported by friends and family who are equally afraid for them, who furthermore can’t visit because of isolation needs. And I often forget that, besides Covid, families have gone through immense social and financial changes. Sometimes communication can be fraught because of that stress. I am trying to be mindful that patients and families come into the hospital with a lot of these burdens, so that, if the conversation takes a tense turn, I will try not to take it personally. Some days are harder than others.
What you are describing isn’t necessarily an innate skill.
Dr. Lee: Absolutely. As have many others, our medical school and residency program has been incorporating communication skills into the standard curriculum, analogous to teaching anatomy or heart failure treatments. We are more aware that handling a difficult conversation isn’t an instinctive thing; that it must be modeled and learned. But I was surprised at how communication in a pandemic, when caretakers can’t see their loved ones, is truly a unique challenge. It is challenging for me despite being in practice for several years.
What will happen when the pandemic subsides? How much of the impact of Covid will stay with you, when dealing with a broken leg, or a patient with osteoporosis?
Dr. Lee: There will be lasting effects of this era on the health-care workforce, but I honestly can’t predict how severe that impact will be or how long-lasting. Already we are seeing health-care workers drop out of the workforce, driven by effects of the pandemic itself, increased workload, or being underpaid.7 This is occurring alongside a national conversation that cannot agree on life-saving interventions such as vaccines. I worry that the current environment will lead to many more dropping out.
What can hospital administrators do now to put stop gaps in place? What advice would you give to them?
Dr. Lee: Workers in each hospital will have unique needs and stressors, so it makes sense that the first step is to provide an opportunity to make their opinions heard. It may be tempting for hospitals to jump on quick fixes such as offering classes in “resilience training,” but that may not be a data-driven solution, particularly if burnout is being driven by an ever increasing workload.
Cheryl K. Lee, MD, an Assistant Professor of Medicine at Northwestern Feinberg School of Medicine, practices internal medicine and pediatrics at Northwestern Memorial and the Ann & Robert H. Lurie Children's Hospital, both in Chicago, IL. She also serves on the Northwestern Medicine Covid Quality Committee and as core clinical faculty in the Internal Medicine Residency.
Is it fair to say that for hospitalists, the pandemic has been a sobering experience, why so?
Dr. Lee: There are several reasons; one stems from the increasing impact of Covid on children. Early in the pandemic, young children, teens, and young adults were not infected or hospitalized at the rate of older adults.1 For those of us who care for hospitalized patients, that early finding was somewhat of a relief, knowing at least one portion of the population wasn’t as heavily affected. In fact, I normally split my time as a pediatric and adult hospitalist, and I was reassigned to work full-time in the adult hospital because so few children had been admitted. But all that changed with the arrival of the highly transmissible Delta variant and the loosening of social distancing and masking guidelines and other regulations. The American Academy of Pediatrics2 reported that, as of October, 8,364 of every 100,000 children have been infected by Covid, largely driven by the summer surge. Furthermore, pediatric Covid hospitalizations increased five-fold in August 2021 as compared to the prior 6 weeks. And these numbers likely underestimate the true impact, as several states did not release complete reports and did not account for long-term sequelae from milder infections.
What other issues were far-reaching for hospitalists?
Dr. Lee: Early in 2020, we were scrambling to learn about a novel, deadly, highly transmissible disease. Some groups in our population were experiencing a high fatality rate, and the medical community had no proven treatments. We felt helpless in caring for these patients who pleaded for our help and ultimately died. When data proved that medications like steroids were effective and the vaccines arrived, I had hoped that the pandemic would be ending. But now with the quick dissemination of false information and the evolution of new variants, we are left caring for seriously ill, unvaccinated patients along with younger patients. The heartbreaking thing is that these are largely preventable tragedies now that we have effective vaccines.
What medications have changed the course of Covid in the hospital?
Dr. Lee: Steroids are interesting; they are a good reminder that Covid has different stages and that we should be mindful of how we treat patients within those particular stages. Simply, Covid infection begins with a phase of viral replication characterized by fevers, cough, loss of taste and smell, and gastrointestinal symptoms. In time, this is followed by a second phase of high inflammation and immune response, sometimes causing hypoxemia and respiratory failure. What we know is that steroids such as dexamethasone reduce mortality, but they are only effective during this second phase, and only in those whose oxygen levels are low enough to require oxygen. This was not an intuitive finding, since steroids do not help, and may harm, those with other viral pneumonias, such as influenza. Steroid use in severe, hypoxemic Covid, however, is life-saving and the mainstay of inpatient care which might include antivirals and interleukin-6 inhibitors3 in select patients. As with steroid use in other patients, physicians should watch their Covid patients for hyperglycemia4 and delirium. That said, steroids provide a mortality benefit that strongly supports their continued use -- in tandem with management of those expected side effects. Last, it is important to note that steroid use has been associated with possible harm when given to those with mild Covid,5 so its use should be avoided, in light of its expected side effects, unless a patient requires supplemental oxygen.
That said, although steroids can be helpful for our sickest patients, vaccines are the best medicine of all because they can allow patients to avoid hospitalization and death -- outcomes that far outweigh what steroids or any other medication can do for the gravely ill.
Given the complexity of the evidence surrounding the treatments for Covid in the hospital, no wonder some people are confused about which medicines work.
Dr. Lee: First, let me say that I have yet to encounter a patient or family member whose motivation to ask questions or question a loved one’s treatment wasn’t grounded in concern and fear for their loved one.
What do they ask about?
Dr. Lee: They ask about alternative treatments, anti-parasitics, even vitamins. I agree with them that there is so much out there about Covid that it is difficult for anyone to know what is true or false. I then explain what therapies are proven – medications such as steroids and supportive care such as oxygen and prone positioning. I also review the lack of good evidence for the alternative treatments that they ask about. It is sometimes surprising to folks that all research isn’t conducted with equal rigor, and that false conclusions can be made based on faulty evidence. A good example is how providers used hydroxychloroquine early in the pandemic, but ultimately it didn’t prove to be helpful. Although we are always hopeful and looking for new therapies, I say, those specific alternatives haven’t worked out. And I end with a promise that I will continue to keep up with the literature and let them know when something new does look promising.
Your responses to the above questions prompts this one: How do physicians who are treating Covid-19 stay on top of what is being learned about Covid-19? At last count, there were 191,968 results in PubMed, found using that sole keyword.
Dr. Lee: One of the amazing things about the Covid era is that members of the scientific community dropped everything to research Covid. But on the flip side, there is now a lot of research out there, and it frankly has become difficult to keep up with it. Our hospital system identified a core group of collaborators with backgrounds such as pharmacy, nursing, infectious disease, pulmonary, and hospital medicine to regularly review the evidence and identify anything that has strong enough evidence to change our system’s clinical practice. Furthermore, I regularly tap consultants in various specialties to help me contextualize new research. And I’ve found it helpful to review the living practice guidelines from the Infectious Disease Society of America and the NIH.3,6
What else has been remarkable about the last 19 months?
Dr. Lee: I have never spent this much time talking with patients and their caregivers. I’ve always been one to talk a lot with families, but it feels like the pandemic has created another level. My guess is that many colleagues are experiencing the same thing. Caring for hospitalized Covid patients is not only intense from a medical standpoint, but also from a psychosocial vantage point. Patients are ill and usually scared, and they are supported by friends and family who are equally afraid for them, who furthermore can’t visit because of isolation needs. And I often forget that, besides Covid, families have gone through immense social and financial changes. Sometimes communication can be fraught because of that stress. I am trying to be mindful that patients and families come into the hospital with a lot of these burdens, so that, if the conversation takes a tense turn, I will try not to take it personally. Some days are harder than others.
What you are describing isn’t necessarily an innate skill.
Dr. Lee: Absolutely. As have many others, our medical school and residency program has been incorporating communication skills into the standard curriculum, analogous to teaching anatomy or heart failure treatments. We are more aware that handling a difficult conversation isn’t an instinctive thing; that it must be modeled and learned. But I was surprised at how communication in a pandemic, when caretakers can’t see their loved ones, is truly a unique challenge. It is challenging for me despite being in practice for several years.
What will happen when the pandemic subsides? How much of the impact of Covid will stay with you, when dealing with a broken leg, or a patient with osteoporosis?
Dr. Lee: There will be lasting effects of this era on the health-care workforce, but I honestly can’t predict how severe that impact will be or how long-lasting. Already we are seeing health-care workers drop out of the workforce, driven by effects of the pandemic itself, increased workload, or being underpaid.7 This is occurring alongside a national conversation that cannot agree on life-saving interventions such as vaccines. I worry that the current environment will lead to many more dropping out.
What can hospital administrators do now to put stop gaps in place? What advice would you give to them?
Dr. Lee: Workers in each hospital will have unique needs and stressors, so it makes sense that the first step is to provide an opportunity to make their opinions heard. It may be tempting for hospitals to jump on quick fixes such as offering classes in “resilience training,” but that may not be a data-driven solution, particularly if burnout is being driven by an ever increasing workload.
References
- L. Shekerdemian, N. Mahmood, K.Wolfe, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (Covid-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020 Sep; 174(9): 1–6.
- Children and Covid-19: State-Level Data Report. American Academy of Pediatrics. Published Oct. 25, 2021. https://www.aap.org/en/pages/2019-novel-coronavirus-Covid-19-infections/children-and-Covid-19-state-level-data-report/
- NIH. Therapeutic Management of Hospitalized Adults with Covid-19. Last updated August 25, 2021. https://www.Covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/
- Sosale A, Sosale B, Kesavadev J, et al. Steroid use during Covid-19 infection and hyperglycemia - What a physician should know. Diabetes Metab Syndr. 2021;15(4):102167. doi:10.1016/j.dsx.2021.06.004
- The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693-704.
- IDSA. IDSA Guidelines on the Treatment and Management of Patients with Covid-19. Last updated November 1, 2021. https://www.idsociety.org/practice-guideline/Covid-19-guideline-treatment-and-management/
- Galvin, G. “Nearly 1 in 5 Health Care Workers Have Quit Their Jobs During the Pandemic.” Morning Consult. https://morningconsult.com/2021/10/04/health-care-workers-series-part-2-workforce/ Accessed November 1, 2021.
References
- L. Shekerdemian, N. Mahmood, K.Wolfe, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (Covid-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020 Sep; 174(9): 1–6.
- Children and Covid-19: State-Level Data Report. American Academy of Pediatrics. Published Oct. 25, 2021. https://www.aap.org/en/pages/2019-novel-coronavirus-Covid-19-infections/children-and-Covid-19-state-level-data-report/
- NIH. Therapeutic Management of Hospitalized Adults with Covid-19. Last updated August 25, 2021. https://www.Covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/
- Sosale A, Sosale B, Kesavadev J, et al. Steroid use during Covid-19 infection and hyperglycemia - What a physician should know. Diabetes Metab Syndr. 2021;15(4):102167. doi:10.1016/j.dsx.2021.06.004
- The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693-704.
- IDSA. IDSA Guidelines on the Treatment and Management of Patients with Covid-19. Last updated November 1, 2021. https://www.idsociety.org/practice-guideline/Covid-19-guideline-treatment-and-management/
- Galvin, G. “Nearly 1 in 5 Health Care Workers Have Quit Their Jobs During the Pandemic.” Morning Consult. https://morningconsult.com/2021/10/04/health-care-workers-series-part-2-workforce/ Accessed November 1, 2021.
Sleep-related hypoxia and COVID-19 outcomes
Key clinical point: Sleep-related hypoxia is associated with worse outcomes in patients with COVID-19.
Major finding: Sleep-related hypoxia was associated with an increased risk for COVID-19-related hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005).
Study details: The data come from a case-control study involving 5,402 individuals who had previously participated in a sleep study, of whom 1,935 tested positive for SARS-CoV-2.
Disclosures: The study was supported by the Neuroscience Transformative Research Resource Development Award (R Mehra). A Milinovich reported ties with various pharmaceutical companies and research organizations. L Aboussouan, L Jehi, R Mehra, and C Pena Orbea reported ties with research organizations and/or publishing companies. The remaining authors declared no competing interests.
Source: Pena Orbea C et al. JAMA Netw Open. 2021 Nov 10. doi: 10.1001/jamanetworkopen.2021.34241.
Key clinical point: Sleep-related hypoxia is associated with worse outcomes in patients with COVID-19.
Major finding: Sleep-related hypoxia was associated with an increased risk for COVID-19-related hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005).
Study details: The data come from a case-control study involving 5,402 individuals who had previously participated in a sleep study, of whom 1,935 tested positive for SARS-CoV-2.
Disclosures: The study was supported by the Neuroscience Transformative Research Resource Development Award (R Mehra). A Milinovich reported ties with various pharmaceutical companies and research organizations. L Aboussouan, L Jehi, R Mehra, and C Pena Orbea reported ties with research organizations and/or publishing companies. The remaining authors declared no competing interests.
Source: Pena Orbea C et al. JAMA Netw Open. 2021 Nov 10. doi: 10.1001/jamanetworkopen.2021.34241.
Key clinical point: Sleep-related hypoxia is associated with worse outcomes in patients with COVID-19.
Major finding: Sleep-related hypoxia was associated with an increased risk for COVID-19-related hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005).
Study details: The data come from a case-control study involving 5,402 individuals who had previously participated in a sleep study, of whom 1,935 tested positive for SARS-CoV-2.
Disclosures: The study was supported by the Neuroscience Transformative Research Resource Development Award (R Mehra). A Milinovich reported ties with various pharmaceutical companies and research organizations. L Aboussouan, L Jehi, R Mehra, and C Pena Orbea reported ties with research organizations and/or publishing companies. The remaining authors declared no competing interests.
Source: Pena Orbea C et al. JAMA Netw Open. 2021 Nov 10. doi: 10.1001/jamanetworkopen.2021.34241.