Frontiers in Immunology (Sep 2022)

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

  • Franziska Sotzny,
  • Igor Salerno Filgueiras,
  • Claudia Kedor,
  • Helma Freitag,
  • Kirsten Wittke,
  • Sandra Bauer,
  • Nuno Sepúlveda,
  • Nuno Sepúlveda,
  • Dennyson Leandro Mathias da Fonseca,
  • Gabriela Crispim Baiocchi,
  • Alexandre H. C. Marques,
  • Myungjin Kim,
  • Tanja Lange,
  • Desirée Rodrigues Plaça,
  • Finn Luebber,
  • Finn Luebber,
  • Frieder M. Paulus,
  • Roberta De Vito,
  • Igor Jurisica,
  • Igor Jurisica,
  • Igor Jurisica,
  • Igor Jurisica,
  • Igor Jurisica,
  • Kai Schulze-Forster,
  • Friedemann Paul,
  • Friedemann Paul,
  • Friedemann Paul,
  • Friedemann Paul,
  • Judith Bellmann-Strobl,
  • Judith Bellmann-Strobl,
  • Judith Bellmann-Strobl,
  • Judith Bellmann-Strobl,
  • Rebekka Rust,
  • Rebekka Rust,
  • Rebekka Rust,
  • Rebekka Rust,
  • Uta Hoppmann,
  • Uta Hoppmann,
  • Uta Hoppmann,
  • Uta Hoppmann,
  • Yehuda Shoenfeld,
  • Yehuda Shoenfeld,
  • Gabriela Riemekasten,
  • Harald Heidecke,
  • Otavio Cabral-Marques,
  • Otavio Cabral-Marques,
  • Otavio Cabral-Marques,
  • Otavio Cabral-Marques,
  • Otavio Cabral-Marques,
  • Carmen Scheibenbogen

DOI
https://doi.org/10.3389/fimmu.2022.981532
Journal volume & issue
Vol. 13

Abstract

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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.

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