Long-term serum spike protein persistence but no correlation with post-COVID syndrome

According to the World Health Organization (WHO) and the Centers for Diseases Control and Prevention (CDC), currently an estimated 3 - 6 % of people suffer from post-COVID condition or syndrome (PCS). A subset meets diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Several studies have reported persistence of SARS-CoV-2 proteins or RNA in serum or tissues of both recovered individuals and PCS patients. In this exploratory study, we investigated whether serum spike protein is associated with PCS and whether it correlates with symptom severity and laboratory biomarkers. We analyzed serum spike protein levels in 121 PCS patients following mild-to-moderate COVID-19, 72 of whom met diagnostic criteria for ME/CFS (post-COVID ME/CFS, pcMECFS). Pre-pandemic seronegative healthy controls (ppHC, n = 32) and post-COVID recovered healthy controls (pcHC, n = 37) after SARS-CoV-2 infection were also included in the study. We found persistent serum SARS-CoV-2 spike protein in a subset of pcHC (11 %), PCS non-ME/CFS patients (2 %), and pcMECFS patients (14 %). There was no significant association with disease severity, symptoms, or laboratory markers. The spike protein concentration was independent of the time since last spike exposure (infection or vaccination). In five spike-positive out of a total of 22 patients who underwent immunoglobulin depletion via immunoadsorption (IA), spike protein was reduced or completely removed after treatment, indicating binding to immunoglobulins. In summary, our study identified serum spike protein in a subset of patients after SARS-CoV-2 infection without evidence for a role in the pathogenesis of PCS.