Abstract: Clinical Rheumatology (2020) 39:2789–2796 https://doi.org/10.1007/s10067-020-05301-2 ORIGINAL ARTICLE Determinants of COVID-19 disease severity in patients with underlying rheumatic disease C. Sieiro Santos 1 & C. Moriano Morales 1 & E. Díez Álvarez 1 & C. Álvarez Castro 1 & A. López Robles 1 & T. Perez Sandoval 1 Received: 4 June 2020 / Revised: 14 July 2020 / Accepted: 17 July 2020 / Published online: 27 July 2020 # International League of Associations for Rheumatology (ILAR) 2020 Abstract Background Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease. Objectives To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain. Methods We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed. Results During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68–83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5–83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3–75.8) and more likely to have arterial hypertension (9 [90%] vs 14 [50%] patients; OR 9 (95% CI 1.0–80.8), p 0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33–108), p 0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33, p 0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16–26), p 0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10–34.7, p 0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23–405.23), p 0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120–220) vs 107.4 (IQR 30–150; p 0.05); lactate dehydrogenase (641.8 (IQR 465.75–853.5) vs 361 (IQR 250–450), p 0.03); serum ferritin (1026 (IQR 228.3– 1536.3) vs 861.3 (IQR 389–1490.5), p 0.04); D-dimer (12,019.8 (IQR 843.5–25,790.5) vs 1544.3 (IQR 619–1622), p 0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before..