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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Aikawa, Nadia Emi ; Kanda Kupa, Leonard de Vinci ; Medeiros-Ribeiro, Ana Cristina ; Schahin Saad, Carla Goncalves ; Neves Yuki, Emily Figueiredo ; Pasoto, Sandra Gofinet ; Rojo, Priscila Tagliaferro ; Rodrigues Pereira, Rosa Maria ; Shinjo, Samuel Katsuyuki ; Sampaio-Barros, Percival Degrava ; Oliveira Andrade, Danieli Castro ; Radu Halpern, Ari Stiel ; Fuller, Ricardo ; Carlos Souza, Fernando Henrique ; Noronha Guedes, Lissiane Karine ; Assad, Ana Paula Luppino ; Bertacini de Moraes, Julio Cesar ; Ugolini Lopes, Michelle Remiao ; de Oliveira Martins, Victor Adriano ; Betancourt, Lorena ; Ribeiro, Carolina Torres ; Sales, Lucas Peixoto ; Bertoglio, Isabela Maria ; Nazario Bonoldi, Virginia Lucia ; Pinheiro Mello, Renata Lys ; Moreira Balbi, Gustavo Guimaraes ; Christovam Sartori, Ana Marli ; Antonangelo, Leila ; Silva, Clovis Artur ; Bonfa, Eloisa

• Document type: Journal article
• Source: ANNALS OF THE RHEUMATIC DISEASES; v. 81, n. 7, p. 8-pg., 2022-03-10.

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. (AU)

• FAPESP's process: 20/09367-8 - Analysis of blood hydroxychlorochine levels in patients with primary Sjogren Syndrome and possible correlation with the disease activity
• Grantee: Lorena Elizabeth Betancourt Villamarín
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/17272-0 - Relevance of monitoring blood levels compared to salivar levels of drugs used in rheumatic autoimmune diseases: adherence and understanding the possible underlying mechanisms involved in effectiveness and in adverse effects
• Grantee: Leonard de Vinci Kanda Kupa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/09937-9 - Analysis of the immune profile of saliva and serum of patients with primary Sjogren's Syndrome
• Grantee: Victor Adriano de Oliveira Martins
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)