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

James K Romine; Huashi Li; Melissa M Coughlin; Jefferson M Jones; Amadea Britton; Harmony L Tyner; Sammantha B Fuller; Robin Bloodworth; Laura J Edwards; Jini N Etoule; Tyler C Morrill; Gabriella Newes-Adeyi; Lauren E W Olsho; Manjusha Gaglani; Ashley Fowlkes; James Hollister; Edward J Bedrick; Jennifer L Uhrlaub; Shawn Beitel; Ryan S Sprissler; Zoe Lyski; Cynthia J Porter; Patrick Rivers; Karen Lutrick; Alberto J Caban-Martinez; Sarang K Yoon; Andrew L Phillips; Allison L Naleway; Jefferey L Burgess; Katherine D Ellingson

doi:10.1093/cid/ciae130

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

Clin Infect Dis. 2024 Mar 11:ciae130. doi: 10.1093/cid/ciae130. Online ahead of print.

Authors

James K Romine¹, Huashi Li¹, Melissa M Coughlin², Jefferson M Jones², Amadea Britton², Harmony L Tyner³, Sammantha B Fuller⁴, Robin Bloodworth⁴, Laura J Edwards⁴, Jini N Etoule⁴, Tyler C Morrill⁴, Gabriella Newes-Adeyi⁴, Lauren E W Olsho⁴, Manjusha Gaglani⁵, Ashley Fowlkes², James Hollister¹, Edward J Bedrick¹, Jennifer L Uhrlaub¹, Shawn Beitel¹, Ryan S Sprissler⁶, Zoe Lyski⁷, Cynthia J Porter¹, Patrick Rivers¹, Karen Lutrick⁸, Alberto J Caban-Martinez⁹, Sarang K Yoon¹⁰, Andrew L Phillips¹⁰, Allison L Naleway¹¹, Jefferey L Burgess¹, Katherine D Ellingson¹

Affiliations

¹ Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, USA.
² National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
³ St. Luke's Regional Health Care System, Duluth, Minnesota, USA.
⁴ Abt Associates, Inc., Rockville, Maryland, USA.
⁵ Baylor Scott & White Health, Temple, Texas, USA.
⁶ University of Arizona Genetics Core, Office for Research, Innovation and Impact, University of Arizona, Tucson, Arizona, USA.
⁷ Department of Immunobiology, University of Arizona, Tucson, Arizona, USA.
⁸ College of Medicine - Tucson, University of Arizona, Tucson, Arizona, USA.
⁹ University of Miami, Miller School of Medicine, Miami, Florida, USA.
¹⁰ University of Utah Health, Rocky Mountain Center for Occupational and Environmental Health, Salt Lake City, Utah, USA.
¹¹ Kaiser Permanente Northwest Center for Health Research, Portland, Oregon, USA.

PMID: 38466720
DOI: 10.1093/cid/ciae130

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.

Keywords: COVID-19; SARS-CoV-2; antibody durability; hybrid immunity; mRNA vaccine.