LAUSR

Several risk factors for severe COVID-19 have been identified1. An important question is whether in addition to these generic risk factors, patients with a potentially altered immune response, either by disease (inflammatory rheumatic diseases (IRDs)) or use of immunomodulatory agents (IA), carry a higher or lower risk of severe COVID-19. In addition, several other potential risk factors for severe COVID-19 have been suggested, such as vitamin D status and specific medication (NSAIDs, ACE-inhibitors)2.To identify risk factors for severe COVID-19, requiring hospitalization, in patients with IRDs.Multicenter, unmatched nested case control study in four rheumatology centers in the Netherlands. Cases are IRD patients requiring hospitalization for COVID-19 between March 1st 2020 and May 31st 2020. Control patients are IRD patients not hospitalized for COVID-19 within this period and were included in a 1:4 ratio. Patient-, disease- and treatment characteristics were extracted (still ongoing) from electronic patient files, and a questionnaire was used to collect additional data (e.g. on behavioral aspects). Potential risk factors for severe COVID-19 were analyzed using unconditional logistic regression, corrected for confounders.77 cases and 198 controls were included. 26 case patients died as a result of COVID-19, 14 were admitted to the ICU. Crude ORs for female sex, age, BMI and presence of one or more comorbidities were 0.46 (95% CI 0.27-0.29), 1.1 (95%CI 1.0-1.1), 1.0 (95%CI 0.98-1.1) and 3.0 (95%CI 1.7-5.2) respectively. Table 1 displays corrected OR, highlighted when OR <0.5/>2.0. Corrected ORs were not significantly increased for any IRD, but a trend for gout was present. Use of hydroxychloroquine (HCQ) shows a protective effect, while use of other csDMARDs than methotrexate or HCQ leads to a higher risk of severe COVID-19. Trends were present for increased risk for rituximab (RTX), glucocorticoids and ACE inhibitors, and protective effect for IL-6R blockers.The outcomes of this study are in agreement with other research regarding risk of severe COVID-19 related to IRDs and use of IA1. The suggested increased risk of severe COVID-19 in RTX use is of concern and should be monitored closely. Strengths of this study include low bias due to behavioral effects as only cases early in the pandemic were included, completeness of the determinants of interest and ultimately, it provides answers to a relevant and urgent question.[1]Williamson, Elizabeth J et al. “Factors associated with COVID-19-related death using OpenSAFELY.” Nature vol. 584,7821 (2020): 430-436.[2]Rizk, John G et al. “Pharmaco-Immunomodulatory Therapy in COVID-19.” Drugs vol. 80,13 (2020): 1267-1292.[3]Rentsch, Christopher T et al. “Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform.” The Lancet Rheumatology vol. 3,1 (2021): e19-e27.Table 1.Corrected ORs for several potential risk factorsPotential risk factorCorrected OR (95% CI)IRDRA*1.38 (0.68 – 2.8)Spondylarthritis0.60 (0.25-1.5)Gout2.8 (0.80-9.8)Polymyalgia0.54 (0.18-1.6)Systemic diseases1.6 (0.49-5.0)DMARDscsDMARDs (any)0.39 (0.17-0.88) Methotrexate0.90 (0.46-1.7)HCQ0.40 (0.16-0.98)Other2.0 (0.99-4.1)bDMARDs (any)0.96 (0.43-2.2) TNF-inhibitors1.0 (0.43-2.6) IL6R-blockers0.43 (0.044 – 4.2)RTX4.5 (0.25-79)tsDMARDs0.89 (0.08-9.8)OtherGlucocorticoids > 10 mg/day2.5 (0.70-9.0)NSAIDs0.82 (0.37-1.8)ACE-inhibitors3.4 (1.6-7.1)Vitamin D sufficient0.77 (0.40-1.5)*incl. unspecified arthritisMerel Opdam Grant/research support from: has received research grants (to the institution) from Gilead, S Benoy: None declared, L.M. Verhoef: None declared, Sandra van Bijnen: None declared, Femke Lamers-Karnebeek: None declared, R.A.M. Traksel: None declared, Petra Vos: None declared, Alfons den Broeder Grant/research support from: has received consultancy honoraria, congress invitations and research grants (to the institution) from Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead. Is coinventor on a rituximab related patent (pending)., Jasper Broen Consultant of: has received consultancy fees from Gilead and Galapagos.