Sustained Cell-mediated but Not Humoral Responses in Rituximab-treated Rheumatic Patients After Vaccination Against SARS-CoV-2

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2023 May 25

PMID 37228039

Authors

Konstantinos Thomas

Ioannis Grigoropoulos

Panagiota Alexopoulou

Emmanouil Karofylakis

Irene Galani

Kyriaki Korina Papadopoulou

Anastasia Tsiavou

Aliki Ntourou

Eleftheria Mavrou

Irina Qevani

Pelagia Katsimbri

Christos Koutsianas

Evgenia Mavrea

Dimitrios Vassilopoulos

Spyros Pournaras

Sotirios Tsiodras

Dimitrios Boumpas

Anastasia Antoniadou

Affiliations

Soon will be listed here.

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.

Citing Articles

Longitudinal Comparison of Three T-Cell Assays and Three Antibody Assays Against SARS-CoV-2 Following Homologous mRNA-1273/mRNA-1273/mRNA-1273 and Heterologous ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naïve Healthcare Workers.

Lee H, Ko G, Lee J, Bae H, Ryu J, Jung J Vaccines (Basel). 2025; 12(12.

PMID: 39772013 PMC: 11679843. DOI: 10.3390/vaccines12121350.

[Corona vaccination under immunosuppression].

Hasseli-Frabel R, Kneitz C, Voll R, Hoyer B Z Rheumatol. 2024; 83(7):544-548.

PMID: 39311952 DOI: 10.1007/s00393-024-01555-2.

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