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Master of Public Health

Hybrid immunity and SARS-CoV-2 antibodies: results of the HEROES-RECOVER prospective cohort study

AUTHORS

Romine JK , Li H , Coughlin MM , Jones JM , Britton A , Tyner HL , Fuller SB , Bloodworth R , Edwards LJ , Etoule JN , Morrill TC , Newes-Adeyi G , Olsho LEW , Gaglani M , Fowlkes A , Hollister J , Bedrick EJ , Uhrlaub JL , Beitel S , Sprissler RS , Lyski Z , Porter CJ , Rivers P , Lutrick K , Caban-Martinez AJ , Yoon SK , Phillips AL , Naleway AL , Burgess JL , Ellingson KD , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024 3 11; ().

ABSTRACT

BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels.

METHODS: Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events.

RESULTS: Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively.

CONCLUSIONS AND RELEVANCE: Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

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