A NEW study has identified inflammatory biomarkers linked to long COVID in patients with systemic autoimmune rheumatic diseases (SARD), suggesting that lower levels of the cytokine IL-18 may contribute to the condition.
Conducted as part of the RheumCARD study, the research analysed 201 patients with SARDs who had recovered from COVID-19 and 47 SARD patients without COVID-19, focusing on cytokine levels and their association with long COVID.
Of the SARD patients with prior COVID-19, 39% reported symptoms lasting 28 days or more, meeting the U.S. Centers for Disease Control and Prevention’s definition of long COVID, while 22% experienced symptoms for over 90 days. The study cohort had a mean age of 56 years, and 81% were female. The majority (60%) had inflammatory arthritis, followed by connective tissue diseases (22%). Treatment profiles revealed that 31% were on conventional synthetic disease-modifying antirheumatic drugs, and 26% used TNF inhibitors.
In terms of immune biomarkers, long COVID patients had significantly lower median levels of IL-18 (199 pg/mL) compared to those without long COVID (221 pg/mL, p=0.001). These findings persisted even after adjusting for age, sex, vaccination status, and viral variant in multivariable regression (β -55 pg/mL, SE 17, p=0.0011). Additionally, reduced levels of CSF2 and CCL7 and elevated IL-2 levels were associated with long COVID.
Subgroup analyses confirmed the robustness of the findings, with consistently lower IL-18 levels observed in patients with inflammatory arthritis (P=0.021), those in remission or low disease activity (P=0.02), and across pre-Omicron (P=0.004) and Omicron variants (P=0.06). Lower IL-18 levels were also observed in cases of long COVID persisting over 90 days and compared to SARD patients without prior COVID-19 (P=0.011).
The results suggest a possible mechanism for long COVID in patients with SARDs, pointing to a blunted immune response rather than hyperinflammation. As IL-18 is linked to inflammasome activation and cell-mediated immunity, these insights could inform the development of targeted treatments and diagnostic tests for long COVID.
Reference
Sparks JA et al. Associations of circulating inflammatory cytokines with long COVID among patients with systemic autoimmune rheumatic diseases. Abstract 2616. ACR Convergence 2024, 14–19 November, 2024.
