학술논문
Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2.
Document Type
Article
Author
Thomas, Κonstantinos; Grigoropoulos, Ioannis; Alexopoulou, Panagiota; Karofylakis, Emmanouil; Galani, Irene; Papadopoulou, Kyriaki Korina; Tsiavou, Anastasia; Ntourou, Aliki; Mavrou, Eleftheria; Qevani, Irina; Katsimbri, Pelagia; Koutsianas, Christos; Mavrea, Evgenia; Vassilopoulos, Dimitrios; Pournaras, Spyros; Tsiodras, Sotirios; Boumpas, Dimitrios; Antoniadou, Anastasia
Source
Subject
*RITUXIMAB
*INTERFERON gamma release tests
*BREAKTHROUGH infections
*COVID-19
*IMMUNIZATION
*COVID-19 vaccines
*CROSS-sectional method
*AUTOIMMUNE diseases
*BLOOD collection
*INTERVIEWING
*ENZYME-linked immunosorbent assay
*DESCRIPTIVE statistics
*RHEUMATISM
*CELLULAR immunity
*
*
*
*
*
*
*
*
*
*
*
*
*
Language
ISSN
1462-0324
Abstract
Objectives B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. Methods Serum and whole blood samples were collected from RTX-treated rheumatic patients 3–6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. Results Sixty patients were studied after a median (IQR) of 179 (117–221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4–10.75) vs 11 (6.75–14.75) grams, (P = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2–4) vs 6 (4–8), P = 0.002] and cumulative dose [4 (3–7) vs 10 (6.25–13) grams, P = 0.002] and had shorter time from last vaccination to sampling [140 (76–199) vs 192 (128–230) days, P = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P = 0.03). Conclusions Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2. [ABSTRACT FROM AUTHOR]