Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People with Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry

Background: Approximately one-third of individuals worldwide have not received a COVID-19 vaccine. While studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases, we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern.
Methods: Patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, rheumatic disease activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; sub-analyses stratified patients according to rheumatic disease types.
Results: Among 19,256 unvaccinated people with rheumatic disease and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell depleting therapy were associated with worse outcomes. In those with connective tissue disease or vasculitis, B-cell depleting therapy was associated with worse outcomes.
Conclusions: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with rheumatic disease. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.