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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive funding but was in part paid for with funds from the NBA COVID-19 Program. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Advarra IRB waived ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data produced in the present study are available upon reasonable request to the authors if approved by research committee governing these protected occupational health data records.