key: cord-0912709-dfq455h6 authors: Evangelatos, Gerasimos; Kouna, Konstantina; Fragoulis, George E; Moschopoulou, Melina; Triantafylli, Maria; Lekka, Antigoni; Iliopoulos, Alexios title: Low levels of anti‐SARS‐CoV‐2 antibodies after vaccination in rituximab‐ treated patients: Comment on article of Simon et al date: 2021-11-01 journal: Arthritis Rheumatol DOI: 10.1002/art.42011 sha: b39b7ed08e6256dbe4a7561592b1c8679f9c628e doc_id: 912709 cord_uid: dfq455h6 nan We read with great interest the study of Simon et al, in which impaired humoral, but not T-cellular response, was observed after vaccination for SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) treated with rituximab (RTX) (1) . The authors report that none of the 8 vaccinated RTX-treated patients developed IgG antibodies against the spike S1 protein and the nucleocapsid of SARS-CoV-2. Moreover, Boyarski et al recently reported increased rates of undetectable titres of anti-SARS-CoV-2 antibodies in patients treated with RTX (p=0.04) (2) . In patients with hematological malignancies treated with RTX, only 0-14% developed serological response to mRNA BNT162b2 vaccine, when RTX was used within 12 months before vaccination (3). On this basis, we examined the antibody response after two doses of SARS-CoV-2 in 11 patients treated with RTX. Seven (63.6%) were female, 9 had diagnosis of rheumatoid arthritis, one of dermatomyositis and one of cryoglobulinemic vasculitis. Patients with past SARS-CoV-2 infection or low IgG were excluded. Patients had received a mean±SD 5.5±3.9 number of RTX cycles before SARS-CoV-2 vaccination and 1 st dose of the vaccine was administered in mean±SD 20.4±13.4 weeks after the last RTX cycle. All, but one, were vaccinated with the SARS-CoV-2 mRNA vaccine BNT162b2. We used Abbott's quantitative chemiluminescent microparticle immunoassay to detect IgG antibodies against SARS-CoV-2 spike protein. In line with the aforementioned studies, only 2 of 11 (18.2%) patients had antibody levels over the cut-off value of 50 AU/mL; the median (IQR) anti-SARS-CoV-2 level was 21.3 (4-28) AU/mL. Our results confirm those from earlier studies showing reduced antibody response after COVID-19 vaccination in patients with IMIDs under RTX (1, 2, 4). RTX treatment has been associated with worse COVID-19 outcomes, such as more severe disease incidence and increased duration of hospitalization (5) . Given that vaccination against SARS-CoV-2 has been highly effective in preventing COVID-19 pneumonia development (6) , it is considered essential for RTX-treated patients to be vaccinated. Nevertheless, RTX treatment has been associated with reduced antibody response after flu and pneumococcal vaccination (7) . Based on these data, ACR suggests that patients under RTX should be better vaccinated for COVID-19 four weeks before the next scheduled cycle and RTX administration should be withheld for 2-4 weeks after the second vaccine dose (8) . However, we observed low levels of anti-SARS-CoV-2 antibodies, despite the first vaccine dose was administered a mean time of 5 months after the last RTX cycle. Mrak et al reported inadequate antibody development also when the first vaccine dose was administered about 6.9 months after the last RTX cycle (4). Indeed, time from last RTX cycle correlates with peripheral B cells count and anti-SARS-CoV-2 antibody levels and the percentage of peripheral B cells is associated with antibody development in vaccinated patients (4) . These data imply that the time interval Accepted Article between last RTX administration and first vaccine dose should be possibly reconsidered. As RTX-treated patients seem to exhibit T-cellular immune responses to SARS-CoV-2 vaccination (1, 4) , the clinical significance of impaired humoral response after vaccination in these patients remains to be elucidated. Brief Report: Humoral and cellular immune responses to SARS-CoV-2 infection and vaccination in B cell depleted autoimmune patients. Arthritis Rheumatol Antibody response to a single dose of SARS-CoV-2 mRNA vaccine in patients with rheumatic and musculoskeletal diseases Between a rock and a hard place: COVID-19 vaccination and patients on rituximab therapy SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 2. Arthritis Rheumatol This article is protected by copyright. All rights reserved.