Clinical Pearls & Morning Reports
Published February 3, 2021
The Coronavirus Efficacy (COVE) phase 3 trial was launched in late July 2020 to assess the safety and efficacy of the mRNA-1273 vaccine in preventing symptomatic SARS-CoV-2 infection. The authors recently reported the results of the primary analysis of this ongoing phase 3 trial. Read the NEJM Original Article here.
Q: What was the efficacy of the mRNA-1273 vaccine in the COVE trial?
A: The COVE trial provides evidence of short-term efficacy of the mRNA-1273 vaccine in preventing symptomatic SARS-CoV-2 infection in a diverse adult trial population. For the primary analysis, 196 cases of Covid-19 were diagnosed: 11 cases in the vaccine group (3.3 per 1000 person-years; 95% confidence interval (CI), 1.7 to 6.0) and 185 cases in the placebo group (56.5 per 1000 person-years; 95% CI, 48.7 to 65.3), indicating 94.1% efficacy of the mRNA-1273 vaccine (95% CI, 89.3 to 96.8%; P<0.001) for the prevention of symptomatic SARS-CoV-2 infection as compared with placebo.
Q: What was learned about the vaccine’s efficacy in secondary analyses?
A: Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. A key secondary end point evaluated the efficacy of mRNA-1273 at preventing severe Covid-19. Thirty participants in the trial had severe Covid-19; all 30 were in the placebo group, and one death among these participants was attributed to Covid-19.
A: Solicited adverse events at the injection site occurred more frequently in the mRNA-1273 group than in the placebo group after both the first dose (84.2%, vs. 19.8%) and the second dose (88.6%, vs. 18.8%). Solicited systemic adverse events occurred more often in the mRNA-1273 group than in the placebo group after the first dose (54.9%, vs. 42.2%) and the second dose (79.4%, vs. 36.5%). The severity of the solicited systemic events increased after the second dose in the mRNA-1273 group. The frequency of unsolicited adverse events, unsolicited severe adverse events, and serious adverse events reported during the 28 days after injection was generally similar among participants in the two groups. No evidence of vaccine-associated enhanced respiratory disease was noted. The anecdotal finding of a slight excess of Bell’s palsy in this trial and in the BNT162b2 vaccine trial arouses concern that it may be more than a chance event, and the possibility bears close monitoring.
A: The trial is ongoing, and a follow-up duration of 2 years is planned. Although the trial showed that mRNA-1273 reduces the incidence of symptomatic SARS-CoV-2 infection, the data were not sufficient to assess asymptomatic infection. Evaluation of the incidence of asymptomatic or subclinical infection and viral shedding after infection are under way, to assess whether vaccination affects infectiousness. The relatively smaller numbers of cases that occurred in older adults and in participants from ethnic or racial minorities and the small number of previously infected persons who received the vaccine limit efficacy evaluations in these groups. Longer-term data from the ongoing trial may allow a more careful evaluation of the vaccine efficacy in these groups. Pregnant women and children were excluded from this trial, and additional evaluation of the vaccine in these groups is planned.