Risk factors for infection, predictors of severe disease and antibody response to COVID-19 in patients with rheumatic diseases in Portugal – a multicentre, nationwide study

In order to identify risk factors for SARS-CoV-2 infection as well as for severe/critical COVID-19 in rheumatic and musculoskeletal diseases (RMDs) patients, we conducted a multicentre observational nationwide study of adult patients prospectively-followed in the Rheumatic Diseases Portuguese Register – Reuma.pt – during the first 6 months of the pandemic. We further evaluated the development of IgG antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in patients with RMDs. We used multivariate logistic regression to compare patients with COVID-19 (COVID-19+) with those who did not develop the disease (COVID-19-) and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. COVID-19+ patients were asked to collect a blood sample for IgG testing ≥ 3 months after infection and results were compared with age-, sex- and sampling date-matched controls. Overall, 179 cases of COVID-19 were registered in Reuma.pt in the period of interest (median age 55 (IQR 20); 76.5% females) in a total of 6404 registered appointments. We found that patients treated with TNF inhibitors had reduced odds of infection (OR=0.16, 95%CI 0.10-0.26, p<0.001), severe disease (OR 0.11, 95%CI 0.01-0.84, p=0.010) and seroconversion rates (OR 0.13, 95%CI 0.02-0.91, p=0.040). Tocilizumab was also associated with a reduced risk of COVID-19 (OR 0.15, 95%CI 0.05-0.41, p<0.001). Older age, major comorbidities (diabetes, hypertension, obesity, cardiovascular disease, chronic pulmonary and kidney disease) and rituximab were associated with an increased risk of infection and worse prognosis, in line with previous reports. Importantly, most patients with inflammatory RMDs (86.2%) were able to develop a robust antibody response after SARS-CoV-2 infection, which was linked with disease severity.