COVID-19 vaccine efficacy in participants with weakened immune systems from four randomized-controlled trials

Amy Sherman; Jessica Tuan; Valeria D Cantos; Oladunni Adeyiga; Scott Mahoney; Ana M Ortega-Villa; Amy Tillman; Jennifer Whitaker; Amanda S Woodward Davis; Brett Leav; Ian Hirsch; Jerald Sadoff; Lisa M Dunkle; Peter B Gilbert; Holly E Janes; James G Kublin; Paul A Goepfert; Karen Kotloff; Nadine Rouphael; Ann R Falsey; Hana M El Sahly; Magdalena E Sobieszczyk; Yunda Huang; Kathleen M Neuzil; Lawrence Corey; Beatriz Grinsztejn; Glenda Gray; Martha Nason; Lindsey R Baden; Cynthia L Gay

doi:10.1093/cid/ciae192

COVID-19 vaccine efficacy in participants with weakened immune systems from four randomized-controlled trials

Clin Infect Dis. 2024 Apr 10:ciae192. doi: 10.1093/cid/ciae192. Online ahead of print.

Authors

Amy Sherman¹, Jessica Tuan², Valeria D Cantos³, Oladunni Adeyiga⁴, Scott Mahoney⁵, Ana M Ortega-Villa⁶, Amy Tillman⁷, Jennifer Whitaker⁸, Amanda S Woodward Davis⁹, Brett Leav¹⁰, Ian Hirsch¹¹, Jerald Sadoff¹², Lisa M Dunkle¹³, Peter B Gilbert⁹, Holly E Janes⁹, James G Kublin⁹, Paul A Goepfert¹⁴, Karen Kotloff¹⁵, Nadine Rouphael¹⁶, Ann R Falsey¹⁷, Hana M El Sahly⁸, Magdalena E Sobieszczyk¹⁸, Yunda Huang⁹, Kathleen M Neuzil¹⁹, Lawrence Corey^{20

9}, Beatriz Grinsztejn²¹, Glenda Gray²², Martha Nason²³, Lindsey R Baden¹, Cynthia L Gay²⁴

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Department of Medicine, Division of Infectious Diseases, Boston, MA, USA.
² Yale School of Medicine, Section of Infectious Diseases, New Haven, CT, USA.
³ Emory University, Division of Infectious Diseases, Atlanta, GA, USA.
⁴ University of California, Los Angeles, Department of Medicine, Division of Infectious Diseases, Los Angeles, CA, USA.
⁵ University of Cape Town, Desmond Tutu HIV Centre, Department of Medicine, Cape Town, South Africa.
⁶ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁷ Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁸ Baylor College of Medicine, Department of Molecular Virology and Microbiology and Section of Infectious Diseases, Department of Medicine, Houston, TX, USA.
⁹ Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, WA, USA.
¹⁰ Moderna Inc., Cambridge, MA, USA.
¹¹ Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
¹² Janssen Vaccines and Prevention, Leiden, Netherlands.
¹³ Novavax, Gaithersburg, MD, USA.
¹⁴ University of Alabama at Birmingham, Department of Medicine, Birmingham, AL, USA.
¹⁵ University of Maryland School of Medicine, Department of Pediatrics and the Center for Vaccine Development and Global Health, Baltimore, MD, USA.
¹⁶ Hope Clinic, Emory University, Atlanta, GA, USA.
¹⁷ University of Rochester, Infectious Disease Division, Rochester, NY, USA.
¹⁸ Columbia University Irving Medical Center, Department of Medicine, New York, NY, USA.
¹⁹ University of Maryland School of Medicine, Center for Vaccine Development and Global Health, Baltimore, MD, USA.
²⁰ University of Washington, Department of Laboratory Medicine and Pathology, Seattle, WA, USA.
²¹ National Institute of Infectious Diseases-Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
²² University of the Witwatersrand, Perinatal HIV Research Unit, Faculty of Health Sciences, Johannesburg, South Africa; South African Medical Research Council, Cape Town, South Africa.
²³ National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA.
²⁴ University of North Carolina at Chapel Hill School of Medicine, Department of Medicine, Division of Infectious Diseases, UNC HIV Cure Center, Chapel Hill, NC, USA.

PMID: 38598658
DOI: 10.1093/cid/ciae192

Abstract

Background: Although the SARS-CoV-2 vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions.

Methods: A post-hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, COVID-19 vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS (NTIS) individuals starting at 14 days after completion of the primary series through the blinded phase for each of the four trials. An analysis of participants living with well-controlled HIV was conducted using the same methods.

Results: 3,852/30,351 (12.7%) Moderna participants, 3,088/29,868 (10.3%) Novavax participants, 3,549/32,380 (11.0%) AstraZeneca participants, and 5,047/43,788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (versus placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants vs NTIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with HIV.

Conclusions: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared to those with non-tempered immune systems in the four COVID-19 vaccine randomized controlled efficacy trials.

Keywords: COVID-19; HIV; Vaccine; immunocompromised; vaccine efficacy.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.