Post-COVID-19 arthritis: is it hyperinflammation or autoimmunity?

Various musculoskeletal and autoimmune manifestations have been described in patients with coronavirus disease 2019 (COVID-19). Objectives: This study aims to investigate the prevalence and etiology of arthritis in post-COVID Egyptian patients. Methods: We included 100 post-COVID Egyptian patients who recovered 6 months ago and assessed several inflammatory and autoimmune markers. Results: The prevalence of post-COVID arthritis was 37%. Ankle, knee, and wrist were the most commonly affected joints. Old age (P = 0.010), smoking (P = 0.001), and arthralgia (P = 0.049) were all linked with post-COVID arthritis. Levels of pretreatment (baseline) interleukin (IL)-6 (46.41 ± 3.67 vs. 24.03 ± 2.46; P = 0.001), as well as 6-month post-COVID C-reactive protein (CRP; 98.49 ± 67.55 vs. 54.32 ± 65.73; P = 0.002), and erythrocyte sedimentation rate (ESR; 109.08 ± 174.91 vs. 58.35 ± 37.87; P = 0.029) were significantly higher in patients with arthritis compared to those without. On the other hand, complement C3 (P = 0.558) and C4 (P = 0.192), anti-nuclear antibodies (P = 0.709), and anti-cyclic citrullinated peptides (anti-CCP; P = 0.855) did not show significant differences. Only pretreatment IL-6 level was the significant single predictor of post-COVID arthritis with an odds ratio (95% confidence interval) of 3.988 (1.460-10.892) and a P-value of 0.007.

The strong association observed with inflammatory markers (ESR and CRP) and the insignificant association with serologic markers of autoimmunity (ANA and anti-CCP) in our study support the notion that the underlying mechanism of post-COVID-19 arthritis is primarily due to the hyperinflammatory process associated with COVID-19 infection, and not the result of an autoimmune reaction. IL-6 levels before therapy can predict post-COVID arthritis allowing for early management.