AUTHOR=Sotzny Franziska , Filgueiras Igor Salerno , Kedor Claudia , Freitag Helma , Wittke Kirsten , Bauer Sandra , Sepúlveda Nuno , Mathias da Fonseca Dennyson Leandro , Baiocchi Gabriela Crispim , Marques Alexandre H. C. , Kim Myungjin , Lange Tanja , Plaça Desirée Rodrigues , Luebber Finn , Paulus Frieder M. , De Vito Roberta , Jurisica Igor , Schulze-Forster Kai , Paul Friedemann , Bellmann-Strobl Judith , Rust Rebekka , Hoppmann Uta , Shoenfeld Yehuda , Riemekasten Gabriela , Heidecke Harald , Cabral-Marques Otavio , Scheibenbogen Carmen TITLE=Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.981532 DOI=10.3389/fimmu.2022.981532 ISSN=1664-3224 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.