Lack of Evidence for Vaccine-Associated Enhanced Disease From COVID-19 Vaccines Among Adults in the Vaccine Safety Datalink

Abstract

Purpose: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19).

Methods: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect.

Results: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness.

Conclusion: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.

Keywords: COVID‐19 vaccines; SARS‐CoV‐2; vaccine safety; vaccine‐associated enhanced disease.

FIGURE 1 ∣

Association of severe disease outcomes and vaccination status among adults hospitalized for COVID-19 in the Vaccine Safety Datalink from March 1, 2021 through October 31, 2021. ATE inverse probability treatment weight factors for all outcomes: age group, race and Hispanic ethnicity, sex, tobacco smoking status, and 10 high-risk conditions for COVID-19: cancer, cardiovascular disease, cerebrovascular disease, dementia, diabetes mellitus, immune compromise, kidney disease, lung disease, obesity, and substance use disorder. ATE outcome adjustment factors: age group, month of admission, influenza vaccination, cardiovascular disease, and diabetes mellitus. ATE, average treatment effect; CI, confidence interval; ICU, intensive care unit; WHO, World Health Organization. *An average treatment effect risk ratio less than 1.0 indicated that being unvaccinated against COVID-19 was associated with score ≥6 on the WHO Clinical Progression Scale, ICU admission, or death.