Article Text
Abstract
Objective To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response.
Methods Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination.
Results ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001).
Conclusions We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.
Trial registration number NCT04754698.
- COVID-19
- autoimmune diseases
- vaccination
- biological therapy
- therapeutics
Data availability statement
All data relevant to the study are included in the article.
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Data availability statement
All data relevant to the study are included in the article.
Footnotes
Handling editor Josef S Smolen
CAS and EB contributed equally.
Contributors NEA, CAS, LdVKK, ACM-R, CGSS, EFNY, SGP and EB conceived and designed the study, participated in data collection and analysis, supervised the clinical data management, and wrote and revised the manuscript. EB is responsible for the overall content as the guarantor. EB and PR organised and supervised the blood collection and vaccination. SGP, VAOM and VLNB supervised the serum processing, SARS-CoV-2-specific antibody ELISA/neutralisation assays and SARS-CoV-2 RT-PCR. NEA, LdVKK, ACM-R, CGSS, EFNY, SGP, PTR, RMRP, SKS, PDS-B, DA, ASRH, RF, FHCS, LKNG, APLA, JCBdM, MRUL, VAOM, LB, CTR, LPS, IMB, RLPM, GGMB, LA, AMCS, CAS and EB collected epidemiological and clinical data and assisted with the identification of SARS-CoV-2 infection and follow-up of patients. PR organised and supervised the vaccination protocol. All authors helped to edit the manuscript.
Funding This study was sponsored by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (#2015/03756-4 to CAS, SGP, NEA and EB; #2019/17272-0 to LdVKK; #2020/09367-8; #2018/09937-9 to VAOM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (#304984/2020-5 to CAS; #305556/2017-7 to RMRP; #303379/2018-9 to SKS; #305242/2019-9 to EB), B3-Bolsa de Valores do Brasil and Chamada Instituto Todos pela Saúde (ITPS 01/2021, proposta C1313 to EB, CAS, NEA and SGP).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.