COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Primary Prevention Heath PT, Galiza EP, Baxter DN, et al. Safety and Efficacy of the NVX-CoV2373 COVID-19 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial. Clin Infect Dis. 2022 Oct 10. pii: 6754597. doi: 10.1093/cid/ciac803.
PICO Terms
adult (P) adverse reactions; safety (O) alpha; B.1.1.7; variant of concern; VOC (P) anti-nucleocapsid protein IgG (O) any infection (O) asymptomatic infection (O) fully vaccinated (I/C) geometric mean titres (O) healthy (P) immunogenicity (O) moderate disease (O) neutralizing antibodies (O) Novavax vaccine; NVX-CoV2373; protein subunit (I/C) placebo (I/C) SARS-CoV-2 spike protein-binding antibodies (O) seroconversion (O) severe disease (O) spike-specific T cell response (O) symptomatic infection (O) vaccine efficacy (O) waning over time (O)
Demographic Information
Geriatric Population
60 years to <70 years
Gender
Female Male
Race
African American Asian Black Hispanic Latino Multiracial White
Abstract

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against COVID-19 in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover; data to the end of the placebo-controlled phase are reported.

METHODS: Adults aged 18-84 years received two doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.

RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (57.4-86.8) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-? secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.

CONCLUSIONS: A two-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster dose may be indicated.

Ratings
Discipline / Specialty Area Score
Internal Medicine
Public Health
Infectious Disease
Comments from MORE raters

Infectious Disease rater

Additional data on the safety and efficacy of the Novavax COVID-19 vaccine (adjuvanted, recombinant protein) is noteworthy for 100% efficacy in preventing severe disease in this randomized, observer-blind, placebo-controlled study. I suspect many practitioners will rely on public health vaccine recommendations rather than the independent study of this paper. However, the benefit at a median of 4.5 months of follow-up in preventing severe disease may attract attention.

Infectious Disease rater

Six times more cases of COVID-19 infection in placebo recipients than in vaccine recipients. The incidence of COVID-19, 1.9% in placebo recipients and 0.3% in vaccine recipients; absolute risk reduction, 1.6; number needed to vaccinate to prevent 1 case of COVID-19 is 62. The study ended in July 2021, so may not apply to current variants. No data on efficacy of booster doses.

Public Health rater

Outstandingly well planned, analysed, and presented study.