Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 A Prospective Cohort Study

被引：255

作者：

Deepak, Parakkal ^{[1
]}

Kim, Wooseob ^{[2
]}

Paley, Michael A. ^{[3
]}

Yang, Monica ^{[13
]}

Carvidi, Alexander B. ^{[11
]}

Demissie, Emanuel G. ^{[9
]}

El-Qunni, Alia A. ^{[3
]}

Haile, Alem ^{[4
]}

Huang, Katherine ^{[1
]}

Kinnett, Baylee

Liebeskind, Mariel J. ^{[5
]}

Liu, Zhuoming ^{[8
]}

McMorrow, Lily E. ^{[3
]}

Paez, Diana ^{[13
]}

Pawar, Niti ^{[9
]}

Perantie, Dana C. ^{[6
]}

Schriefer, Rebecca E. ^{[3
]}

Sides, Shannon E. ^{[6
]}

Thapa, Mahima ^{[2
]}

Gergely, Mate

Abushamma, Suha ^{[1
]}

Akuse, Sewuese ^{[1
]}

Klebert, Michael ^{[1
,6
]}

Mitchell, Lynne ^{[3
]}

Nix, Darren ^{[1
]}

Graf, Jonathan ^{[11
]}

Taylor, Kimberly E. ^{[10
]}

Chahin, Salim ^{[6
]}

Ciorba, Matthew A. ^{[1
]}

Katz, Patricia ^{[11
]}

Matloubian, Mehrdad ^{[12
]}

O'Halloran, Jane A. ^{[7
]}

Presti, Rachel M. ^{[7
]}

Wu, Gregory F. ^{[1
,6
]}

Whelan, Sean P. J. ^{[8
]}

Buchser, William J. ^{[5
]}

Gensler, Lianne S. ^{[13
]}

Nakamura, Mary C. ^{[14
]}

Ellebedy, Ali H. ^{[2
]}

Kim, Alfred H. J. ^{[3
]}

机构：

[1] Washington Univ, Dept Med, Div Gastroenterol, Sch Med, 660 South Euclid Ave,Campus Box 8124, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Immunobiol, 660 South Euclid Ave,Campus Box 8118, St Louis, CA 63110 USA

[3] Washington Univ, Sch Med, Dept Med, Div Rheumatol, 660 South Euclid Ave,Campus Box 8045, St Louis, CA 63110 USA

[4] Washington Univ, Sch Med, Clin Trials Unit, 660 South Euclid Ave,Campus Box 8051, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Genet, 660 South Euclid Ave,Campus Box 8232, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Dept Neurol, Neuroimmunol Sect, 660 South Euclid Ave Campus Box 8232, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Dept Med, Div Infect Dis, 660 South Euclid Ave, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Dept Mol Microbiol, 660 South Euclid Ave,Campus Box 8230, St Louis, MO 63110 USA

[9] Univ Calif San Francisco, 505 Parnassus Ave, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, 513 Parnassus Ave,MSB 859, San Francisco, CA 94117 USA

[11] Univ Calif San Francisco, 1001 Potrero Ave, San Francisco, CA 94110 USA

[12] Univ Calif San Francisco, 533 Parnassus Ave, San Francisco, CA 94117 USA

[13] Univ Calif San Francisco, 400 Parnassus Ave, San Francisco, CA 94143 USA

[14] San Francisco VA Hlth Care Syst, 4150 Clement St,111R, San Francisco, CA 94121 USA

来源：

ANNALS OF INTERNAL MEDICINE | 2021年 / 174卷 / 11期

关键词：

INFLUENZA VACCINATION; RESPONSES; ADULTS; DRUGS;

D O I：

10.7326/M21-1757

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. Primary Funding Source: The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

引用

页码：1572 / +

页数：22

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