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  • Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

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Epidemiology
Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases
  1. Nádia Emi Aikawa1,
  2. Leonard de Vinci Kanda Kupa1,
  3. Ana Cristina Medeiros-Ribeiro1,
  4. Carla Goncalves Schahin Saad1,
  5. Emily Figueiredo Neves Yuki1,
  6. Sandra Gofinet Pasoto1,
  7. Priscila Tagliaferro Rojo1,
  8. Rosa Maria Rodrigues Pereira1,
  9. Samuel Katsuyuki Shinjo1,
  10. Percival Degrava Sampaio-Barros1,
  11. Danieli Castro Oliveira Andrade1,
  12. Ari Stiel Radu Halpern1,
  13. Ricardo Fuller1,
  14. Fernando Henrique Carlos Souza1,
  15. Lissiane Karine Noronha Guedes1,
  16. Ana Paula Luppino Assad1,
  17. Julio Cesar Bertacini de Moraes1,
  18. Michelle Remiao Ugolini Lopes1,
  19. Victor Adriano de Oliveira Martins1,
  20. Lorena Betancourt1,
  21. Carolina Torres Ribeiro1,
  22. Lucas Peixoto Sales1,
  23. Isabela Maria Bertoglio1,
  24. Virginia Lucia Nazario Bonoldi1,
  25. Renata Lys Pinheiro Mello1,
  26. Gustavo Guimaraes Moreira Balbi1,
  27. Ana Marli Christovam Sartori2,
  28. Leila Antonangelo3,
  29. Clóvis Artur Silva4,
  30. Eloisa Bonfa1
  1. 1 Rheumatology Division, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
  2. 2 Infectious Disease Department, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
  3. 3 Central Laboratory Division, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
  4. 4 Pediatric Rheumatology Unit, Instituto da Criança e do Adolescente, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
  1. Correspondence to Eloisa Bonfa, Rheumatology Division, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo - Av. Dr. Arnaldo, 455, sala 3190 - Cerqueira César, São Paulo – SP – Brazil, ZIP-code 01246-903 E-mail – eloisa.bonfa@hc.fm.usp.br, Sao Paulo, SP, Brazil; eloisa.bonfa{at}hc.fm.usp.br

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.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/annrheumdis-2021-222096

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    Data availability statement

    All data relevant to the study are included in the article.

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    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.