ABSTRACT
BACKGROUND: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy. METHODS: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine. FINDINGS: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFi-treated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. CONCLUSIONS: Vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) will likely be required to prevent SARS-CoV-2 infection in this susceptible population. FUNDING: This study was supported by grants and contracts from the NIH (R01 AI157155, R01AI151178, and HHSN75N93019C00074; NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014; and Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051).
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines/therapeutic use , Hepatitis Delta Virus , Humans , RNA, Messenger/genetics , Spike Glycoprotein, Coronavirus , Tumor Necrosis Factor-alpha , Vaccines, Synthetic , mRNA VaccinesABSTRACT
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 mRNA-based 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.