A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases

Abstract

Background: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs).

Methods: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome.

Results: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region.

Conclusions: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Keywords: Autoimmune rheumatic diseases; Glucocorticoid; Hydroxychloroquine; Immunosuppressants; Outcome; Risk factors; SARS-CoV-2 infection.

Fig. 1

Results of bivariate analysis to assess the factors associated with the risk of COVID-19 infection. Significant values in Multivariate analysis; Gender (p = 0.001), DM (p = 0.001), Lung disease (p < 0.001), Glucocorticoid (7.5-20 mg) (p = 0.04), CYC (p < 0.001), Rituximab (p = 0.003). Abbreviations RA rheumatoid arthritis, SLE systemic lupus erythematosus, DM diabetes mellitus, HTN hypertension, CYC cyclophosphamide, TNFi tumor necrosis factor alpha inhibitor, HCQ hydroxychloroquine, ACEi angiotensin converting enzyme inhibitor, ARB angiotensin receptor blocker