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

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Sotzny, Franziska ; Filgueiras, Igor Salerno ; Kedor, Claudia ; Freitag, Helma ; Wittke, Kirsten ; Bauer, Sandra ; Sepulveda, Nuno ; Mathias da Fonseca, Dennyson Leandro ; Baiocchi, Gabriela Crispim ; Marques, Alexandre H. C. ; Kim, Myungjin ; Lange, Tanja ; Placa, Desiree 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

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 13, p. 17-pg., 2022-09-27.

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. (AU)

• FAPESP's process: 20/16246-2 - Holistic characterization of T cell exhaustion in patients with Zika
• Grantee: Dennyson Leandro Mathias da Fonseca
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Otávio Cabral Marques
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/11710-2 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with Dengue
• Grantee: Desirée Rodrigues Plaça
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/07972-1 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Gabriela Crispim Baiocchi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)