Recombinant adjuvanted zoster vaccine and reduced risk of COVID-19 diagnosis and hospitalization in older adults

Background: Vaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California. Methods: In a cohort design, adults aged ≥50 years who received ≥1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression. Results: In the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received ≥1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86). Conclusion: RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.