Vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), especially mRNA vaccines, have been shown to be highly immunogenic [1]. As of November 2021, the Omicron variant has been designated as a variant of concern by the Centers for Disease Control and Prevention and is characterized by high transmissibility, highlighting the importance of vaccination [2]. However, an attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with autoimmune disease (AID) or other causes of immunodepression (ID), and this status has been associated with an increased risk of COVID-19 infection despite vaccination [3,4].

Studies have demonstrated an enhanced humoral response to third-dose SARS-CoV-2 vaccination in immunosuppressed transplant patients [5], and data about the immunogenicity of booster vaccination in other immunosuppressed populations have been published but need to be confirmed and clarified [6]. This is particularly the case for patients receiving anti-CD20 therapy, such as rituximab (RTX), which was a major concern in the context of the coronavirus pandemic. Several studies have investigated the outcomes of COVID-19 in patients with rheumatological diseases. In a large registry study, the risk of severe COVID-19 (i.e. admission to the intensive care unit or death) and length of hospital stay were found to be increased in patients receiving anti-CD20 after adjusting for confounding factors such as age, sex and comorbidities [7]. In addition, the shorter time between the last RTX infusion and COVID-19 infection in patients with severe COVID-19 compared to those with mild or moderate disease suggested that these observed effects were linked to RTX induced B-cell depletion [8]. Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy [9], but few data are available on SARS-CoV-2 vaccines. Furthermore, the isolated evaluation of the humoral response (by serology) incompletely assesses vaccine immunogenicity and data on T-cell immunity are needed. It has been shown that the evolution towards severe forms of COVID-19 is partly dependent on cellular immunity and an evaluation of cellular responses to vaccination is necessary, especially in patients with a poor humoral response [10]. Several validated methods are available to assess the cellular response, but their use in clinical practice remains to be clarified.

The aim of this study was to characterise, in a real-life cohort of ID patients, with or without AID and receiving or not anti-CD20, the humoral and cellular immune responses against specific antigens of SARS-CoV-2 at different times after completion of the vaccination protocol, as well as their correlation and possible associated factors. The report also contains a meta-analysis of data from similar studies in the literature in order to support the results.