LAUSR

We read with great interest the recent article by Fiedman and Winthrop reporting a patient with granulomatosis with polyangiitis (GPA) being treated with rituximab (RTX), recurrent SARSCoV-2 disease 2019 (COVID-19) and no detectable SARSCoV-2 seroresponse after recovery. AntiCD20 therapy impairs humoral response, theoretically increasing the risk of prolonged SARSCoV-2 infection and shedding as well as subsequent reinfection. We have recently reported a patient with GPA under maintenance therapy with RTX and SARSCoV-2 infection. Here, we report further details on antiCD20 therapy with RTX, serological response to SARSCoV-2 infection, virus elimination and corresponding B cell numbers. This case highlights that B cell numbers in patients with rheumatic diseases treated with RTX could associate with serological response to SARSCoV-2 infection, which is particularly relevant as RTX may also impair the immunogenicity of SARSCoV-2 vaccines. An 80yearold man had received a diagnosis of GPA in 2014 with biopsyconfirmed renal vasculitis and no history of pulmonary manifestation. After remission induction therapy, he received RTX at a dose of 500 mg every 6 months as maintenance therapy. The last infusion was in March 2019 with persistent B cell depletion: 0% CD19 B cells in September 2019, 0,13% CD19 B cells in December 2019, 2,7% CD19 B cells in February 2020 (normal range 6%–19%). In March 2020, the patient presented to the emergency department with a 2week history of productive cough and his oxygenation was 85% on room air (figure 1A). An initial nasopharyngeal swab was negative for SARSCoV-2 RNA but positive for influenza A RNA. Because of worsening respiratory failure, the patient required mechanical ventilation. A tracheal aspirate was tested positive for SARSCoV-2 RNA. Subsequently, the patient expired due to multiorgan failure. Serological response to SARSCoV-2 infection was confirmed at day 29 after admission revealing serum levels of 2.16 for IgA and 8.21 for IgG (reference ratios <0.8, EUROIMMUN, Lübeck, Germany), associated with tracheal aspirate tested negative for SARSCoV-2 RNA (figure 1A). Urinary measurements of SARSCoV-2 nucleocapsid protein (SARSCoV-2 N, KIT40588, Sino Biological, Beijing, China) confirmed systemic viral infection with decreasing levels during course of disease (figure 1B). Serological response to confirmed SARSCoV-2 infection and attenuated systemic viral spread correlated with B cell reconstitution (17.73% CD19 B cells, figure 1C). These observations indicate that B cell numbers in patients with rheumatic diseases treated with RTX could associate with SARSCoV-2 serological response and virus elimination. To our knowledge, this is the first report of a relationship between B cell numbers, SARSCoV-2 serological response and virus elimination in a patient with GPA on antiCD20 therapy with RTX. It remains unclear why initial nasopharyngeal swabs for SARSCoV-2 RNA were negative in our case, possibly attributed to the patient’s immunocompromised state. However, COVID-19 was confirmed in the tracheal aspirate. AntiCD20 therapies prevent the formation of protective antibodies, leading to an increased risk of prolonged SARSCoV-2 infection or even reinfection. 2 This has implications for SARSCoV-2 vaccination, which may not be effective in RTXtreated patients. Therefore, clinicians using RTX may consider delaying RTX application or testing for reconstitution of B cells to allow for vaccination, although both may not always be feasible. Finally, further studies are necessary to determine the exact effect of antiCD20 therapy on SARSCoV-2 vaccines and whether delayed dosing improves vaccine immunogenicity. Our observation that seroresponse to SARSCoV-2 infection correlated with the reconstitution of B cells is of importance and implicates that assessment of B cell numbers in patients with rheumatic diseases treated with RTX could further improve the timing of SARSCoV-2 vaccination. This underscores the need for further studies to investigate the effects of specific rheumatic diseases and antiCD20 therapy on the efficacy and durability of the antibody response to SARSCoV-2.