Cellular and humoral responses after second and third SARS-CoV-2 vaccinations in patients with autoimmune diseases treated with rituximab: specific T cell immunity remains longer and plays a protective role against SARS-CoV-2 reinfections

• Published in: Frontiers in immunology 2023-04, Vol.14, p.1146841-1146841
• Main Authors: Egri, Natalia, Calderón, Hugo, Martinez, Robert, Vazquez, Mario, Gómez-Caverzaschi, Verónica, Pascal, Mariona, Araújo, Olga, Juan, Manel, González-Navarro, Europa Azucena, Hernández-Rodríguez, José
• Format: Article
• Language: English
• Subjects: anti CD-20; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Viral; Autoimmune Diseases - drug therapy; cellular response; COVID - 19; COVID-19 Vaccines; Humans; humoral response; Immunoglobulin G; Immunology; Reinfection; rituximab; Rituximab - therapeutic use; SARS-CoV-2; SARS-CoV-2 vaccines; T-Lymphocytes; Vaccination
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1146841

Humoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated. This study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection. Ten COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded. Nine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose. Rituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.