Effect of immunosuppression on the immunogenicity of mrna vaccines to sars-cov-2 a prospective cohort study

Parakkal Deepak, Wooseob Kim, Michael A. Paley, Monica Yang, Alexander B. Carvidi, Emanuel G. Demissie, Alia A. El-Qunni, Alem Haile, Katherine Huang, Baylee Kinnett, Mariel J. Liebeskind, Zhuoming Liu, Lily E. McMorrow, Diana Paez, Niti Pawar, Dana C. Perantie, Rebecca E. Schriefer, Shannon E. Sides, Mahima Thapa, Maté GergelySuha Abushamma, Sewuese Akuse, Michael Klebert, Lynne Mitchell, Darren Nix, Jonathan Graf, Kimberly E. Taylor, Salim Chahin, Matthew A. Ciorba, Patricia Katz, Mehrdad Matloubian, Jane A. O'Halloran, Rachel M. Presti, Gregory F. Wu, Sean P.J. Whelan, William J. Buchser, Lianne S. Gensler, Mary C. Nakamura, Ali H. Ellebedy, Alfred H.J. Kim

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Background: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear. Objective: To determine the immunogenicity of mRNAbased SARS-CoV-2 vaccines in patients with CID. Design: Prospective observational cohort study. Setting: Two U.S. CID referral centers. Participants: Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination. Measurements: Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination. Results: Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n=17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n=10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n=48), tumor necrosis factor inhibitors (n=39), and Janus kinase inhibitors (n=11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies. Limitations: Small sample that lacked demographic diversity, and residual confounding. Conclusion: Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.

Original languageEnglish
Pages (from-to)1572-1585
Number of pages14
JournalAnnals of internal medicine
Volume174
Issue number11
DOIs
StatePublished - Nov 1 2021

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