COVID-19

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Key clinical point: A meta-analysis has identified 10 key risk factors for mortality in hospitalized patients with COVID-19.

Major finding: The significant mortality-related risk factors in hospitalized patients with COVID-19 included older age, male sex, smoking, obesity, cardiovascular disease, diabetes, hypertension, chronic obstructive pulmonary disease, acute kidney injury, and elevated D-dimer levels.

Study details: The data come from a meta-analysis of 42 studies involving 423,117 patients with COVID-19.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Dessie ZG et al. BMC Infect Dis. 2021 Aug 21. doi: 10.1186/s12879-021-06536-3.

Key clinical point: A meta-analysis has identified 10 key risk factors for mortality in hospitalized patients with COVID-19.

Major finding: The significant mortality-related risk factors in hospitalized patients with COVID-19 included older age, male sex, smoking, obesity, cardiovascular disease, diabetes, hypertension, chronic obstructive pulmonary disease, acute kidney injury, and elevated D-dimer levels.

Study details: The data come from a meta-analysis of 42 studies involving 423,117 patients with COVID-19.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Dessie ZG et al. BMC Infect Dis. 2021 Aug 21. doi: 10.1186/s12879-021-06536-3.

Key clinical point: A meta-analysis has identified 10 key risk factors for mortality in hospitalized patients with COVID-19.

Major finding: The significant mortality-related risk factors in hospitalized patients with COVID-19 included older age, male sex, smoking, obesity, cardiovascular disease, diabetes, hypertension, chronic obstructive pulmonary disease, acute kidney injury, and elevated D-dimer levels.

Study details: The data come from a meta-analysis of 42 studies involving 423,117 patients with COVID-19.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Dessie ZG et al. BMC Infect Dis. 2021 Aug 21. doi: 10.1186/s12879-021-06536-3.

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.