Real-world evidence on effectiveness of booster or additional doses of COVID-19 vaccine is limited.
Using patient-level data from 50 sites in the U.S. National COVID Cohort Collaborative (N3C), we estimated COVID-19 booster vaccine effectiveness compared to full vaccination alone (completed 2 doses mRNA or 1 dose Janssen vaccine). At each month following full vaccination, we created comparable cohorts of patients with boosters propensity-score matched to those without boosters by age, sex, race/ethnicity, comorbidities, geographic region, prior COVID-19 infection, and calendar month of full vaccination. Booster efficacy was evaluated among patients with and without immunosuppressed / compromised conditions (ISC; HIV infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer). We used Cox regression models to estimate hazards of breakthrough infection (COVID-19 diagnosis after last dose of vaccine) and logistic regression models to compare the risk of death ?45 days after a breakthrough infection in the boosted vs. matched non-boosted groups.
By 11/18/2021, 656390 patients had received full vaccination, and 125409 fully vaccinated had received an additional booster (median time from last vaccine to booster dose: 7.4 months, IQR:6.6, 8.2). At completion of full vaccination, median age was 50 (IQR 33-64) years, 43% male, 50% white, 11% Black, 18% Latinx, 4.8% Asian American/Pacific Islander, and 20% had ISC. People receiving a booster were more likely to be older, male, white, and have ISC. Booster vaccine was significantly associated with a reduced hazard of breakthrough infection (Table). Booster efficacy ranged from 46% (booster receipt 1-4 months after full vaccination) to 83% (receipt 7 months after full vaccination) in people without ISC. Vaccine efficacy was lower, ranging from 43%-65%, in ISC patients (Table). Compared to fully vaccinated patients without booster receipt, patients with booster had an 83% (OR: 0.17, 95% CI: 0.11, 0.28) reduced risk of COVID-19 related death, independent of demographics, geographic region, comorbidities, ISC, prior COVID-19 infection, and time of full vaccination.
A booster dose of COVID-19 vaccine has high effectiveness in reducing breakthrough infection risk among all fully vaccinated individuals, though only with moderate effectiveness among ISC patients. Nonetheless, booster vaccination significantly reduced risk for COVID-19 related death regardless of ISC status.