Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases
Authors: Nádia Emi Aikawa, Leonard de Vinci Kanda Kupa, Ana Cristina Medeiros-Ribeiro, Carla Goncalves Schahin Saad, Emily Figueiredo Neves Yuki, Sandra Gofinet Pasoto, Priscila Tagliaferro Rojo, Rosa Maria Rodrigues Pereira, Samuel Katsuyuki Shinjo, Percival Degrava Sampaio-Barros, Danieli Castro Oliveira Andrade, Ari Stiel Radu Halpern, Ricardo Fuller, Fernando Henrique Carlos Souza, Lissiane Karine Noronha Guedes, Ana Paula Luppino Assad, Julio Cesar Bertacini de Moraes, Michelle Remiao Ugolini Lopes, Victor Adriano de Oliveira Martins, Lorena Betancourt, Carolina Torres Ribeiro, Lucas Peixoto Sales, Isabela Maria Bertoglio, Virginia Lucia Nazario Bonoldi, Renata Lys Pinheiro Mello, Gustavo Guimaraes Moreira Balbi, Ana Marli Christovam Sartori, Leila Antonangelo, Clóvis Artur Silva, Eloisa Bonfa
Journal: Annals of the Rheumatic Diseases (2022)

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&lt;0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p&lt;0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p&lt;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&lt;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&lt;0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p&lt;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&lt;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&lt;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 .