Coronavirus COVID-19 Update for June 8, 2021

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Clinical Reports

Association of Simulated COVID-19 Vaccination and Nonpharmaceutical Interventions With Infections, Hospitalizations, and Mortality Vaccination against SARS-CoV-2 has the potential to significantly reduce transmission and COVID-19 morbidity and mortality. The relative importance of vaccination strategies and nonpharmaceutical interventions (NPIs) is not well understood. The purpose of this study was to assess the association of simulated COVID-19 vaccine efficacy and coverage scenarios with and without NPIs with infections, hospitalizations, and deaths. Participants An established agent-based decision analytical model was used to simulate COVID-19 transmission and progression from March 24, 2020, to September 23, 2021. The model simulated COVID-19 spread in North Carolina, a US state of 10.5 million people. A network of 1 017 720 agents was constructed from US Census data to represent the statewide population. Scenarios of vaccine efficacy (50% and 90%), vaccine coverage (25%, 50%, and 75% at the end of a 6-month distribution period), and NPIs (reduced mobility, school closings, and use of face masks) maintained and removed during vaccine distribution were used. Simulation outcomes suggest that removing NPIs while vaccines are distributed may result in substantial increases in infections, hospitalizations, and deaths. Furthermore, as NPIs are removed, higher vaccination coverage with less efficacious vaccines can contribute to a larger reduction in risk of SARS-CoV-2 infection compared with more efficacious vaccines at lower coverage. These findings highlight the need for well-resourced and coordinated efforts to achieve high vaccine coverage and continued adherence to NPIs before many prepandemic activities can be resumed.

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. Aim of this study to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended.

Small Airways Disease is a Post-Acute Sequelae of SARS-CoV-2 Infection The sequelae of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized. Adults with confirmed COVID-19 who remained symptomatic more than thirty days following diagnosis were enrolled and classified as ambulatory, hospitalized or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests and chest computed tomography (CT) findings were compared across groups and to healthy controls. CT images were quantitatively analyzed using supervised machine-learning to measure regional ground glass opacities (GGO) and image-matching to measure regional air trapping. Comparisons were performed using univariate analyses and multivariate linear regression. Of the 100 patients enrolled, 67 were in the ambulatory group. All groups commonly reported cough and dyspnea. Pulmonary function testing revealed restrictive physiology in the hospitalized and ICU groups but was normal in the ambulatory group. Among hospitalized and ICU patients, the mean percent of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than in ambulatory patients (3.7%, P<0.001). The mean percentage of total lung affected by air trapping was 25.4%, 34.5% and 27.2% in the ambulatory, hospitalized and ICU groups and 7.3% in healthy controls (P<0.001). Air trapping measured by quantitative CT correlated with the residual volume to total lung capacity ratio (RV/TLC; ρ=0.6, P<0.001). Air trapping is present in patients with post-acute sequelae of COVID-19 and is independent of initial infection severity, suggesting obstruction at the level of the small airways. The long-term consequences are not known.

Antiviral Therapeutics and Vaccines

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease Objective of this study was to investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

Diagnostics

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease Objective of this study was to investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.