A study of 94 unvaccinated adults with rheumatoid arthritis or spondyloarthritis who contracted COVID-19 found that rituximab was associated with reduced humoral and cellular immunity. The cohort included 46 patients with rheumatoid arthritis and 48 with spondyloarthritis (mean age, 53 years; 66% women). Twenty household members without autoimmune disease served as controls.
Treatments included methotrexate (MTX) alone (n=17), anti–tumor necrosis factor (TNF) monotherapy (n=24), anti-TNF plus MTX (n=23), rituximab (n=11), interleukin-17 inhibitors, and Janus kinase inhibitors. Patients were followed at 1, 3, 6, and 12 months postinfection and again after vaccination. No SARS-CoV-2 RNA was detected in stool, blood, or nasal samples, indicating no viral persistence.
Humoral responses were preserved in most groups. Among rituximab recipients, 4 of 11 (36%) lacked detectable anti-Spike IgG and 5 of 11 (45%) lacked IgA antibodies after infection. Levels remained significantly lower than other groups after vaccination (mean interval from infection to last rituximab infusion, 4.5 ± 2.5 months).
CD4+ T-cell activation was preserved across all treatments. In contrast, 63% of rituximab-treated patients had undetectable SARS-CoV-2–specific CD8+ T-cell activation, compared with 18% in controls and TNF inhibitor users, and 33% in those on IL-17 inhibitors. Anti-Spike IgG levels correlated with CD8+ activation (R = 0.4; P = .0022).
Four patients developed severe COVID-19 with greater than 50% lung involvement, all on MTX monotherapy; two required intensive care. Comorbidities included obesity, hypertension, diabetes, and prior myocardial infarction.
Vaccination increased antibody levels and Spike-specific memory B-cell frequencies in most groups but not significantly in rituximab or IL-17 inhibitor users.
“Rituximab therapy was associated with a reduced frequency of SARS-CoV-2–specific activated CD8+ T cells. Similar results were seen with EBV and influenza peptides, suggesting broader effects on viral immunity,” said Maxime Beretta, Institut Pasteur and University Paris Cité, Paris, France.
Despite weakened humoral and CD8+ responses, CD4+ T-cell proliferation was preserved, supporting partial adaptive immunity under immunosuppressive therapy.
The authors reported no conflicts of interest.
Source: RMD Open
