Autoimmune Markers Persist Two Years After COVID-19

A study published in an international medical research journal examined autoantibody expression in patients with Long Covid two years after hospital discharge from Covid-19 infection. Long Covid may partly result from immune alterations caused by SARS-CoV-2, including hyperinflammation, loss of immune tolerance, excessive NET (neutrophil extracellular trap) production, molecular mimicry, and immune dysregulation. According to the authors, an estimated 10% of those infected with Covid-19 develop Long Covid; in hospitalized patients, the incidence is 50–70%. Viral particles have been found to persist for up to 4 months after initial infection, leading to prolonged immune activation. 

The study included 55 participants aged 21–85 years who had tested positive for SARS-CoV-2. Blood samples were collected 2 years post-discharge and analyzed for inflammatory and autoimmune markers, then compared with a control group of 21 individuals with no prior history of COVID-19. Forty-four patients also completed a health questionnaire; the most frequently reported symptoms two years after infection included headache, muscle weakness in the arms or legs, confusion or lack of concentration, a “pins and needles” sensation, shortness of breath, and persistent muscle pain (in that order). Less frequent symptoms included skin rashes and joint swelling. 

Among the 55 Covid-19 patients, 47.3% had reactive ANA, 3.6% had reactive rheumatoid factor (RF), and 20% had elevated CRP levels (not 120%). Anti-CCP antibodies were negative in all patients. 

ANA autoantibodies have distinct fluorescence patterns with clinical associations. The most common pattern in this study was the nuclear fine-speckled pattern (27%), which can be associated with systemic lupus erythematosus (SLE), systemic sclerosis, and autoimmune myositis overlap syndromes. The authors note that ANA testing is not sufficient to diagnose autoimmune diseases, but is a valuable screening tool. “Among the seven reactive samples, three patients exhibited symptoms consistent with SLE, including joint pain or swelling and a tingling sensation.” Additional biomarkers recorded in serum, such as CRP and RF, have been associated with rheumatoid arthritis and other autoimmune conditions. 

Only five participants had received a COVID-19 vaccine, and autoantibody positivity showed minimal overlap with vaccination status. The authors conclude that “it is plausible that the observed autoimmune markers are associated with the infection itself rather than an immunization response.”

Citation

Bianchi, C.C.R., Gritte, R.B., Klauss, P.H.A., & Leal, N.F.S.M. (2025). Detection of autoantibodies in severe COVID-19 patients two years after hospital discharge. Brazilian Journal of Medical and Biological Research, 58, e14927.