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. 2024 Feb 1;63(2):534-541.
doi: 10.1093/rheumatology/kead236.

Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2

Κonstantinos Thomas  1 , Ioannis Grigoropoulos  1 , Panagiota Alexopoulou  1 , Emmanouil Karofylakis  1 , Irene Galani  1 , Kyriaki Korina Papadopoulou  2 , Anastasia Tsiavou  2 , Aliki Ntourou  3 , Eleftheria Mavrou  3 , Irina Qevani  3 , Pelagia Katsimbri  3 , Christos Koutsianas  4 , Evgenia Mavrea  4 , Dimitrios Vassilopoulos  4 , Spyros Pournaras  2 , Sotirios Tsiodras  1 , Dimitrios Boumpas  1   3 , Anastasia Antoniadou  1
Affiliations

Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2

Κonstantinos Thomas et al. Rheumatology (Oxford). .

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.

Keywords: SARS-CoV-2; breakthrough infection; cell-mediated immunity; rituximab.

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Figures

Figure 1.
Figure 1.
Distribution of combined SARS-CoV-2 specific cell mediated and humoral immune responses
See this image and copyright information in PMC

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