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Correspondence on “SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response”by Bonelli et al
  1. Maurizio Benucci1,
  2. Arianna Damiani2,
  3. Maria Infantino3,
  4. Mariangela Manfredi3,
  5. Valentina Grossi3,
  6. Barbara Lari3,
  7. Francesca Li Gobbi4,
  8. Piercarlo Sarzi Puttini5
  1. 1 Rheumatology Unit, San Giovanni di Dio Hospital, Azienda USL Toscana Centro, Firenze, Italy
  2. 2 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy
  3. 3 Immunology and Allergology Laboratory, San Giovanni di Dio Hospital, Florence, Italy
  4. 4 Rheumatology Unit, San Giovanni di Dio Hospital, Firenze, Italy
  5. 5 Rheumatology Unit, ASST-Fatebenefratelli L. Sacco University Hospital, University of Milan, Milan, Italy
  1. Correspondence to Dr Maurizio Benucci, Rheumatology Unit S.Giovanni di Dio Hospital, Azienda USL Toscana centro, Firenze, Toscana, Italy; maubenucci{at}

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We have read the interesting research by Bonelli et al on the role of rituximab in vaccination for SARS-CoV-2. In the data on five patients, two had repopulated B cells and had antibodies to SARS-CoV-2 RBD after vaccination.1 In our experience, we evaluated a group of patients with rheumatoid arthritis who had received the last infusion of rituximab 6 months earlier (group A, four patients), a group of patients who had received the last dose of rituximab 9 months earlier (group B, five patients) and finally a group of patients who had received rituximab 12 months earlier (group C, five patients). All patients received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine 21 days apart. Patients underwent evaluation of the lymphocyte subpopulations with determinations of the B-lymphocyte population (CD27-naive, CD27+ memory, CD38+, CD20+ and CD19+) evaluated by flow cytometry (FACS CANTO II, BD Biosciences), before the vaccination and 3 weeks after the second dose of vaccine. The value of anti-SARS-CoV-2 Spike RBD IgG antibodies (IgG antibodies against S1-protein quantified by FEIA ThermoFisher, Uppsala, Sweden) was determined 3 weeks after the second vaccine dose. All patients were in clinical remission at the time of vaccination and discontinued methotrexate in the week of the first and second vaccine administrations according to published recommendations.2 3 Table 1 shows the characteristics of the sample of the 14 patients. The median levels (min–max) of anti-SARS-CoV-2 Spike RBD IgG antibodies levels (binding antibody units (BAU)/mL) were in the different groups as followings: group A 294 (0.70–569), group B 764 (164–1632), group C 638 (0.70–16320). Differences between the three groups were not statistically significative (p=0.536). Statistical analysis performed with Pearson’s correlation coefficient highlighted the following correlations between antibody quantitative levels and lymphocyte subpopulations: IgG anti-SARS-CoV-2 RBD/CD19 cells/mcl=0.7126, p=0.0039; IgG anti-SARS-CoV-2 RBD/CD20 cells/mcl=0.599, p=0.0236; IgG anti-SARS-CoV-2 RBD/CD27-naive cells/mcl=0.557, p=0.386. In the multiple linear regression model, only CD19 cells’ mcl levels maintained a significance as a predictor of IgG anti-SARS-CoV RBD levels with an estimated beta coefficient of 4.105 (p=0.004). A previous study in 126 patients focused on the role of rituximab in vaccination for SARS-CoV-2.4 Another recent study published in the Annals of the Rheumatic Diseases shows that only patients who had repopulated for B lymphocytes exhibited an immune response to the SARS-CoV-2 vaccine. In the study, 11 patients repopulated but only 7 responded.5 The data from our study show that the time of 9 months since the last infusion of rituximab is sufficient to achieve an immune response, and this can be assessed by the reappearance of circulating CD27-naive CD20+CD19+B lymphocytes. Another aspect to evaluate is the number of treatment exposure cycles in our series 6.07±2.27, which can limit the repopulation of B lymphocytes over time. In conclusion, careful evaluation of peripheral B cell maturation may help the clinician to determine the right time to vaccinate patients treated with rituximab for rheumatic diseases.

Table 1

Demographic, clinical and laboratory charateristics of patients under RTX treatment

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  • 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.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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