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Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion. HLAB27 HLAB HLA B HLA-B2 infections clearance HIV However SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- (SpA COVID19 COVID 19 COVID-1 ReumaCoVBrasil ReumaCoV Brasil multicenter observational Brazil 2009, 2009 , (2009) status ReumaCovBrasils ReumaCov s subanalysis cases (cases control group diagnosis transplantation excluded diagnosis, (diagnosis treatment outcomes ventilation death, death death) comorbidities medication REDCap (REDCap database models program 20 5 5% 24th th 202 2021 15 8 55.5% 555 55 (55.5% 6 44.4% 444 44 4 (44.4% COVID19. 19. N 92 60.1% 601 60 1 440 0 44. 111 11 11. longterm long term 11.7 117 7 (11. 99 9 9. years. . years) 73.2% 732 73 (73.2% distancing smoking body index, index index) 71.8% 718 71 (71.8% 9.15% 915 (9.15% IL17 IL 17 IL-1 antagonists COVID19, 19, 64 753 75 3 75.3 vs 48 48% respectively 0.514. 0514 0.514 514 0.514) addition infection Interestingly arthritis extramusculoskeletal extra musculoskeletal 7. 34 3. B2 5.7 57 (5. 411 4.1 135 13 13. 148 14. 0.594. 0594 0.594 594 0.594) died medications CONEP, CONEP (CONEP) 30186820210018807 30186820 1001 8807 30186820.2.1001.8807 REBEC RBR33YTQC. RBR33YTQC RBRYTQC RBR 33YTQC. 33YTQC YTQC RBR-33YTQC inclusion HLAB2 HLA-B SARS-CoV COVID1 COVID- 200 (2009 55.5 (55.5 44.4 (44.4 60.1 (11 73.2 (73.2 71.8 (71.8 9.15 91 (9.15 IL1 IL- 75. 051 0.51 51 5. (5 41 4. 059 0.59 59 (CONEP 3018682021001880 3018682 100 880 30186820.2.1001.880 (200 55. (55. (44. 60. (1 73. (73. 71. (71. 9.1 (9.1 05 0.5 ( 301868202100188 301868 10 88 30186820.2.1001.88 (20 (55 (44 (73 (71 (9. 0. 30186820210018 30186 30186820.2.1001.8 (2 (4 (7 (9 3018682021001 3018 30186820.2.1001. 301868202100 301 30186820.2.1001 30186820210 30 30186820.2.100 3018682021 30186820.2.10 301868202 30186820.2.1 30186820.2. 30186820.2 30186820.