Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity.

Abstract

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic  criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom  severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels  targeting several G-protein coupled receptors (GPCR). In this exploratory study,  we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly  GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them  fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and  asymptomatic post COVID-19 controls (n=40) were also included in the study as  control groups. We found lower levels for various AABs in PCS compared to at  least one control group, accompanied by alterations in the correlations among  AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1,  and ADRA2A as the strongest classifiers (AABs stratifying patients according to  disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom  severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms  were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study  identified dysregulation of AAB against various receptors involved in the  autonomous nervous system (ANS), vaso-, and immunoregulation and their  correlation with symptom severity, pointing to their role in the pathogenesis of  PCS.