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We read with great interest the article published by D’Silva et al.1 The authors reported three patients with inadequate antibody response to SARS-CoV-2 infection, two of whom received rituximab (RTX). Presence of antispike or antinucleocapsid IgG antibodies is strongly associated with reduced reinfection rates following the COVID-19.2 RTX is an anti-CD 20 monoclonal antibody that depletes B cells. Both T cell-dependent and T cell-independent immune responses against various infections agents are drastically reduced up to 6 months following RTX infusion.3 4 Here we report the antibody response to SARS-CoV-2 infection in five patients with autoimmune rheumatic disease on RTX therapy.
In our centre 224 patients with autoimmune rheumatic diseases had RT-PCR proven COVID-19 infection between March 2020 and December 2020. Of these, five patients had received RTX therapy within 18 months. The titres of IgG antibodies against Spike protein (anti-S) (VITROS immunodiagnostic kit electrochemiluminescence immunoassay (ECLIA)) and the antinucleocapsid (anti-N) (Elecsys anti-SARS-CoV-2 ECLIA) were estimated as per manufacturer’s instructions.
Out of five patients, four had rheumatoid arthritis, and one patient had systemic lupus erythematosus (table 1). The median age of the patients was 51 (31–54.5) years. Four patients had mild COVID-19 while one patient was asymptomatic. All except one patient developed protective anti-S antibody. Out of the three patients who had undetectable B cells at the time of infection, two developed anti-S antibody following COVID 19. Two patients, one with detectable B cells and the other with non-detectable B cells, did not develop the anti-N antibody. The one patient who did not have either antibody had been on RTX for 4 years and had received a 500 mg of RTX infusion with complete peripheral B cell depletion 3 months prior to the onset of COVID-19.
The patients in our cohort who were on RTX had a good outcome and developed adequate titres of protective antibodies despite having undetectable B cells. Recently, Loarce-Martos and associates reported severe disease in patients receiving RTX following SARS-CoV-2 infection.5 They reported severe COVID-19 in 8 out of 13 patients (65%) and a mortality rate of 23%. However, compared with our cohort, the average age was much higher in their cohort. Our cohort was exposed to a lower median RTX dose, which might account for less severe COVID-19 in our cohort. B cells may have a comparatively lesser role in the clearance of virions, as shown in the patients with agammaglobulinaemia who had COVID-19.6 However, neutralising antibodies are pivotal in the prevention of reinfection and reactivation of the virus. Patients on RTX therapy tend to have inadequate antibody response, resulting in a higher risk of reinfection.2 7 However, we have shown that an adequate titre of protective antibodies develop in patients with rheumatic diseases despite B cell depletion with RTX. Whether similar antibody response is generated following vaccination in RTX treated patients need to be explored in future studies…
Contributors Study concept and design: PS and SKC. Acquisition of the clinical and laboratory data: ARM, SS and SASB. Acquisition and interpretation of laboratory data: VS. Drafting and editing paper: PS, SKC and SA. Critical revision of the manuscript: PS and SA. All authors critically reviewed and approved the final manuscript for publication.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The institutional ethical committee, Sree Sudheendra Medical Mission No: IEC/2020/21.
Provenance and peer review Not commissioned; internally peer reviewed.