COVID-19 pill study; new vaccine recommendation plus data on waning efficacy, low risk of postvaccine myocarditis; updates on experimental treatments

Data on molnupiravir, the COVID-19 pill developed by Merck Sharp and Dohme, was published by the New England Journal of Medicine on Dec. 16. The manufacturer-funded phase 3 trial randomized unvaccinated adults with mild to moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe illness to either 800 mg of molnupiravir (n=716) or placebo (n=717) for five days. An interim analysis was conducted when 50% of the target enrollment had been followed through day 29. It found significantly lower risk of hospitalization or death with molnupiravir (7.3% vs. 14.1%; difference, −6.8 percentage points [95% CI, −11.3 to −2.4 percentage points]; P=0.001). “Given the compelling efficacy and safety results obtained at the time of the interim analysis, the independent data monitoring committee recommended an early stop to recruitment of new participants in the trial,” the authors said. A subsequent analysis of all recruited participants found a smaller difference between groups: 6.8% versus 9.7% (difference, −3.0 percentage points; 95% CI, −5.9 to −0.1 percentage points). The authors noted that the smaller effect was due to a decline in the rate of hospitalization and death in the placebo group, which cannot be explained. Subgroup analyses were largely consistent with the overall study results, but in some subgroups, including patients with previous SARS-CoV-2 infection, low baseline viral load, or diabetes, the results favored placebo. One death was reported in the molnupiravir group versus nine in the placebo group. Adverse events were similar between groups. An accompanying editorial noted that the drug was licensed for use in the U.K. on Nov. 4 and is under consideration by the FDA.

The CDC recommended the two mRNA COVID-19 vaccines over the Johnson & Johnson (Janssen) vaccine on Dec. 16. The agency's Advisory Committee on Immunization Practices voted to do so after reviewing data on the rate of thrombosis with thrombocytopenia syndrome (TTS) in recipients of the Johnson & Johnson vaccine. On Dec. 14, the FDA updated its fact sheets on the Johnson & Johnson vaccine and added a contraindication to its administration in individuals with a history of TTS following receipt of any adenovirus-vectored COVID-19 vaccine.

An analysis of the mRNA vaccines, which included more than 5 million patients treated by the Veterans Affairs (VA) health care system, found that their effectiveness seven or more days after the second dose was 69% (95% CI, 67% to 70%) against infection and 86% (95% CI, 82% to 89%) against SARS-CoV-2-related death. The authors of the study, which was published by Annals of Internal Medicine on Dec. 21, concluded that in their elderly, diverse, high-comorbidity population, vaccine effectiveness against infection was lower than previously reported. An Ideas and Opinions article, also published by Annals on Dec. 21, explained why it's difficult to get accurate data on the waning of vaccine efficacy. “The issue is that a study with higher- and lower-risk participants (in other words, risk heterogeneity) can create an illusion of waning vaccine efficacy (VE) over time even when the effect of the vaccine on each individual is not changing, or it can exaggerate the estimated magnitude of true individual waning VE,” the authors explained.

The incidence of myocarditis and myopericarditis after receipt of an mRNA vaccine was assessed by a Danish study published by The BMJ on Dec. 16. It identified 269 participants with myocarditis or myopericarditis (40% ages 12 to 39 years and 73% male). Among the more than 3 million recipients of the Pfizer-BioNTech vaccine, the adjusted hazard ratio (HR) for these complications was 1.34 (95% CI, 0.90 to 2.00) with an absolute rate of 1.4 per 100,000. Among almost 500,000 Moderna recipients studied, the adjusted HR was 3.92 (95% CI, 2.30 to 6.68) and the absolute rate was 4.2 per 100,000, leading the study authors to note that the “absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups.”

Finally, the NIH updated its guidelines on treatment of COVID-19 on Dec. 16 to reflect updated data on monoclonal antibodies, colchicine, fluvoxamine, and additional experimental treatments.