@article{b175e6fbda334b2baf6d799e2f82b1d2,
title = "Effect of immunosuppression on the immunogenicity of mrna vaccines to sars-cov-2 a prospective cohort study",
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.",
author = "Parakkal Deepak and Wooseob Kim and Paley, {Michael A.} and Monica Yang and Carvidi, {Alexander B.} and Demissie, {Emanuel G.} and El-Qunni, {Alia A.} and Alem Haile and Katherine Huang and Baylee Kinnett and Liebeskind, {Mariel J.} and Zhuoming Liu and McMorrow, {Lily E.} and Diana Paez and Niti Pawar and Perantie, {Dana C.} and Schriefer, {Rebecca E.} and Sides, {Shannon E.} and Mahima Thapa and Mat{\'e} Gergely and Suha Abushamma and Sewuese Akuse and Michael Klebert and Lynne Mitchell and Darren Nix and Jonathan Graf and Taylor, {Kimberly E.} and Salim Chahin and Ciorba, {Matthew A.} and Patricia Katz and Mehrdad Matloubian and O'Halloran, {Jane A.} and Presti, {Rachel M.} and Wu, {Gregory F.} and Whelan, {Sean P.J.} and Buchser, {William J.} and Gensler, {Lianne S.} and Nakamura, {Mary C.} and Ellebedy, {Ali H.} and Kim, {Alfred H.J.}",
note = "Funding Information: Grant Support: This research was funded and supported by The Leona M. and Harry B. Helmsley Charitable Trust, the Washington University Digestive Disease Research Core Center (NIDDK P30DK052574), the Washington University Rheumatic Diseases Research Resource-Based Center (NIAMS P30AR073752), The Judy Miniace Research Fund for the Washington University Lupus Clinic, the Washington University Institute of Clinical and Translational Sciences (ICTS) grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS), and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051 for the Washington University Infectious Diseases Clinical Research Unit COVID sample collection. The UCSF investigators were funded by a Seeding Bold Ideas Grant from the Marcus Program in Precision Medicine Innovation, PREMIER, a NIAMS P30 Center (P30AR070155), and the Russell/Engleman Rheumatology Research Center. This study utilized samples obtained from the Washington University School of Medicine's COVID-19 biorepository, which is supported by the Barnes-Jewish Hospital Foundation, the Siteman Cancer Center grant P30CA091842 from the National Cancer Institute of the NIH, and the Washington University ICTS grant UL1TR002345 from the NCATS of the NIH. Dr. Deepak is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn's & Colitis Foundation. Dr. Paley is supported by the Rheumatology Research Foundation. Dr. Ciorba is supported by R01DK109384 and by the Lawrence C. Pakula MD IBD Education and Innovation Fund and Pfizer (IIS #61798927). Dr. Wu is supported by the National Institute of Neurological Disorders and Stroke (R01NS106289) and the National Multiple Sclerosis Society (RG-1802-30253). Drs. Nakamura and Gensler are supported by the San Francisco VA Health Care System. Drs. O{\textquoteright}Halloran, Presti, and Ellebedy are supported by NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. Dr. Ellebedy is also supported by NIAID grant U01AI141990, NIAID Centers of Excellence for Influenza Research and Surveillance contracts HHSN272201400006C and HHSN272201400008C, and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. Dr. Alfred Kim is supported by the Rheumatology Research Foundation, NIH/NIAMS P30 AR073752, and PCORI SDM2017C28224. Publisher Copyright: {\textcopyright} 2021 American College of Physicians. All rights reserved.",
year = "2021",
month = nov,
day = "1",
doi = "10.7326/M21-1757",
language = "English",
volume = "174",
pages = "1572--1585",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
number = "11",
}