July 19, 2021

Coronavirus (COVID-19) Update: July 13, 2021
The U.S. Food and Drug Administration today announced the following actions taken in its ongoing response effort to the COVID-19 pandemic: Today, the FDA is announcing revisions to the vaccine recipient and vaccination provider fact sheets for the Johnson & Johnson (Janssen) COVID-19 Vaccine to include information pertaining to an observed increased risk of Guillain-Barré Syndrome (GBS) following vaccination. GBS is a neurological disorder in which the body’s immune system damages nerve cells, causing muscle weakness, or in the most severe cases, paralysis. Based on an analysis of Vaccine Adverse Event Reporting (VAERS) data, there have been 100 preliminary reports of GBS following vaccination with the Janssen vaccine after approximately 12.5 million doses were administered. Of these reports, 95 of were serious and required hospitalization. There was one reported death. Each year in the United States, an estimated 3,000 to 6,000 people develop GBS. Most people fully recover from the disorder. GBS has also been observed at an increased rate associated with certain vaccines, including certain seasonal influenza vaccines and a vaccine to prevent shingles.  Although the available evidence suggests an association between the Janssen vaccine and the increased risk of GBS, it is insufficient to establish a causal relationship. No similar signal has been identified with the Moderna and Pfizer-BioNTech COVID-19 vaccines. FDA continues to work with its partner in vaccine safety surveillance, the CDC, to monitor reports of GBS following vaccination with the Janssen COVID-19 Vaccine. Importantly, the FDA has evaluated the available information for the Janssen COVID-19 Vaccine and continues to find the known and potential benefits clearly outweigh the known and potential risks.

Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
The authors systematically assessed the benefits and harms of the use of ivermectin (IVM) in COVID-19 patients. Published and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 22, 2021 in five engines. Primary outcomes were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes included viral clearance and severe AEs. The risk of bias (RoB) was evaluated using Cochrane RoB 2·0 tool. Inverse variance random effect meta-analyses were performed. with quality of evidence (QoE) evaluated using GRADE methodology. Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. COVID-19 disease severity was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 0.37, 95%CI 0.12 to 1.13, very low QoE) or LOS vs. controls (MD 0.72 days, 95%CI −0.86 to 2.29, very low QoE). AEs, severe AE, and viral clearance were similar between IVM and controls (all outcomes: low QoE). Subgroups by the severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality in three RCTs at high RoB was reduced with IVM. In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay, or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have an effect on AEs or severe AEs. IVM is not a viable option to treat COVID-19 patients.

Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States
In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, authors evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. Results Among 1210 participants, the median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was the most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but the effectiveness was lower in the immunosuppressed population.

Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination
Authors describe the 8-month durability of humoral and cellular immune responses in 20 participants who received the Ad26.COV2.S vaccine in one or two doses (either 5×10¹⁰ viral particles or 10¹¹ viral particles) and in 5 participants who received placebo. These data show that the Ad26.COV2.S vaccine-elicited durable humoral and cellular immune responses with minimal decreases for at least 8 months after immunization. In addition, an expansion of neutralizing antibody breadth against SARS-CoV-2 variants was observed over this time period, including against the more transmissible B.1.617.2 variant and the partially neutralization-resistant B.1.351 and P.1 variants, which suggests maturation of B-cell responses even without further boosting. The durability of immune responses elicited by the Ad26.COV2.S vaccine was consistent with the durability recently reported for an Ad26-based Zika vaccine. Longitudinal antibody responses to mRNA Covid-19 vaccines have also been reported for 6 months but with different kinetics of decreasing titers. The durability of humoral and cellular immune responses 8 months after Ad26.COV2.S vaccination with increased neutralizing antibody responses to SARS-CoV-2 variants over time, including after single-shot vaccination, further supports the use of the Ad26.COV2.S vaccine to combat the global Covid-19 pandemic.

Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19
Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications. In this phase 3 trial, authors randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19–related hospitalization or death from any cause by day 29. A total of 1035 patients underwent randomization and received an infusion of bamlanivimab–etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab–etesevimab group had a Covid-19–related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, −4.8 percentage points; 95% confidence interval [CI], −7.4 to −2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab–etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19–related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, −1.20; 95% CI, −1.46 to −0.94; P<0.001). Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19–related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load.