Booster Protection Against Omicron Infection in a Highly Vaccinated Cohort

Background: Evaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2 emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization; however, the real-world impact on reducing incident SARS-CoV-2 infections across specific variants is not yet clear. Objectives: Assess the impact of COVID-19 boosters on protection against SARS-CoV-2 infection in a real-world setting from a highly vaccinated (99%) population curated from a linked database with test results, vaccination history, patient demographics, and genomic sequencing information from the National Basketball Association (NBA). Methods: In this population, 1,613 fully vaccinated staff and players (median age 34.5 years, 88% male) who tested at least once between 1 December 2021 and 5 January 2022, were analyzed. Individuals were tested at the time of reporting any symptom, regardless of severity, after known exposure per self-report or contact tracing and/or during enhanced surveillance. Boosted individuals (n=1260) were compared to fully vaccinated and booster eligible individuals (n=162), defined as 2 months post-JNJ-78436735 or 5-months post-second dose of mRNA vaccine. Individuals not yet eligible for a booster and those who recovered from COVID-19 between 1 November and 30 November, 2021 (n=25) were examined in secondary analyses but excluded from the primary comparison. Individuals who were not fully vaccinated (n=27) or who received a booster within 14 days during or prior to the observation period (n=916) were excluded. Results: In this closely monitored population, fully vaccinated booster-eligible individuals were 2.6 times more likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent SARS-CoV-2 infection found that non-boosted individuals were at greater risk of infection compared with boosted individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by primary vaccination type with overlapping confidence intervals. No hospitalizations or deaths were observed in this cohort. Genetic sequencing confirmed 93% of infections to be Omicron (among n=330 sequenced). Conclusions: These results highlight the protective benefit of boosters against incident SARS-CoV-19 infection, not only for severe symptoms and death. Assessment of booster effectiveness remains vital for COVID-19 vaccines as new variants of SARS-CoV-2 emerge, as there is still uncertainty around performance in real-world settings. These data are needed to convince the general public that boosters remain effective at preventing in the spread of COVID-19.