Determinants of COVID-19 disease severity in patients with underlying rheumatic disease

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 admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (p = 0.003), dyslipidaemia (p = 0.01), cardiovascular disease (p = 0.02) and interstitial lung disease (p = 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (p = 0.05), interstitial lung disease (p = 0.03), cardiovascular disease (p = 0.03) and dyslipidaemia (p = 0.01).

Conclusions: Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19. Key Points • Most patients recover from COVID-19. • The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study. • Rheumatic disease activity might be associated with mortality.

Keywords: Biologic; COVID-19; Disease activity; Hospitalized; Hydroxychloroquine; Immunosuppressive; Inflammation; Mortality; Rheumatology; Spain.