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From HHV-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID.
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  • Michael Maes,
  • Abbas F. Almulla,
  • Xiaoou Tang,
  • Kristina Stoyanova,
  • Aristo Vojdani
Michael Maes
Sichuan Academy of Medical Sciences and Sichuan People's Hospital

Corresponding Author:[email protected]

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Abbas F. Almulla
King Chulalongkorn Memorial Hospital Department of Psychiatry
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Xiaoou Tang
Sichuan Academy of Medical Sciences and Sichuan People's Hospital
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Kristina Stoyanova
Medicinski universitet-Plovdiv Farmacevticen fakultet
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Aristo Vojdani
Immunosciences Lab Inc
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Abstract

Background: Inflammation and autoimmune responses contribute to the pathophysiology of Long COVID, and its affective and chronic fatigue syndrome (CFS) symptoms, labeled “the physio-affective phenome.” Objectives: To investigate whether Long COVID and its physio-affective phenome are linked to autoimmunity to the tight junction proteins, zonulin and occludin (ZOOC), and immune reactivity to lipopolysaccharides (LPS), and whether the latter are associated with signs of human herpes virus-6 reactivation (HHV-6), autoimmunity directed against oligodendrocyte and neuronal proteins, including myelin basic protein (MBP). Methods: IgA /IgM/IgG responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), HHV-6, ZOOC, and neuronal proteins, C-reactive protein (CRP) and advanced oxidation protein products (AOPP), were measured in 90 Long COVID patients and 90 healthy controls. The physio-affective phenome was conceptualized as a factor extracted from physical and affective symptom domains. Results: Neural network identified IgA directed to LPS (IgA-LPS), IgG-ZOOC, IgG-LPS, and IgA-ZOOC as the most important variables associated with Long COVID diagnosis with an area under the ROC curve of 0.755. Partial Least Squares analysis showed that 40.9% of the variance in the physio-affective phenome was explained by CRP, IgA-MPB and IgG-MBP. A large part of the variances in both autoimmune responses to MBP (36.3-39.7%) was explained by autoimmunity (IgA and IgG) directed to ZOOC. The latter was strongly associated with indicants of HHV-6 reactivation, which in turn was associated with increased IgM-SARS-CoV-2. Conclusions: Autoimmunity against components of the tight junctions and increased bacterial translocation may be involved in the pathophysiology of Long COVID’s physio-affective phenome.
Submitted to Journal of Medical Virology
Submission Checks Completed
Assigned to Editor
Reviewer(s) Assigned
03 Jul 2024Reviewer(s) Assigned
03 Jul 2024Review(s) Completed, Editorial Evaluation Pending
22 Jul 2024Editorial Decision: Revise Minor
23 Jul 20241st Revision Received
24 Jul 2024Submission Checks Completed
24 Jul 2024Assigned to Editor
24 Jul 2024Review(s) Completed, Editorial Evaluation Pending
26 Jul 2024Reviewer(s) Assigned
06 Aug 2024Editorial Decision: Accept