COVID-19 and Incident Systemic Rheumatic Disease – Is There a Link?

Study authors determined the potential association between COVID-19 and subsequent diagnosis with a systemic rheumatic disease, in a correspondence paper published in Lancet Rheumatology. Using a case series study, the authors noted that a small number of patients developed incident rheumatic disease following infection with SARS-CoV-2, suggesting that COVID-19 may accelerate or trigger progression to clinical autoimmunity.

Study authors queried the electronic medical records of patients at a major healthcare system in Massachusetts between January 30 and November 10, 2020. Patients with a positive SARS-CoV-2 test result were matched with control participants with a negative test result by SARS-CoV-2 test timing (±5 days), age (±5 years), and sex. The primary outcome was incident systemic rheumatic disease, defined as a diagnosis occurring after the initial SARS-CoV-2 test. Patients with a prevalent rheumatic disease diagnosis were excluded from the analysis. Two rheumatologists independently assessed patient medical records to verify rheumatic disease diagnosis and onset. Descriptive statistics were used to summarize findings, and the clinical characteristics of each rheumatic disease case were explored.

The study cohort included 15,284 patients (mean age, 47±20 years) with a positive SARS-CoV-2 test result and 15,284 matched participants (mean age, 46±20 years) with a negative test result. A total of 54% of the total cohort were women. A total of 6 and 5 cases of incident rheumatic disease were identified among patients and control participants, respectively. Among patients with SARS-CoV-2, 3 developed a rheumatic disease within 1 week of receiving their positive COVID-19 test result. All 3 patients were admitted to the hospital for symptoms related to the systemic rheumatic disease. The other 3 patients developed the systemic rheumatic disease more than 2 months following the initial positive test result. The diagnoses for these patients included inflammatory arthritis, giant cell arteritis, inflammatory myopathy, antiphospholipid syndrome, and Sjögren syndrome. Among the matched participants, 4 were diagnosed with polymyalgia rheumatica between 30 and 129 days after SARS-CoV-2 testing. The other patient developed seronegative rheumatoid arthritis 100 days after testing.

Regarding the potential causal relationship between SARS-CoV-2 infection and incident rheumatic disease, the study authors  hypothesized that COVID-19 may “trigger de novo rheumatic disease by inducing type I interferonopathy…[or] accelerate the progression of preexisting subclinical autoimmunity into clinical disease.”

However, the similar rate of incident rheumatic disease among participants without COVID-19 may indicate that the cases of systemic rheumatic diagnoses may have been a matter of chance. Study authors also noted that some patients may have sought SARS-CoV-2 testing due to symptoms from an undiagnosed rheumatic condition, thus introducing bias.

However, the study authors concluded, “Despite these limitations, ours is the first study to our knowledge to systematically identify incident systemic rheumatic diseases within a large health-care system that included a comparator group. Further research is needed to delineate potential links between COVID-19 and autoimmunity.”

Disclosure: Two study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Hsu TY-T, D’Silva KM, Patel NJ, Fu X, Wallace ZS, Sparks JA. Incident systemic rheumatic disease following COVID-19. Lancet Rheumatol. Published online April 6, 2021. doi:10.1016/S2665-9913(21)00106-5