Evidence map›Paper›PMID 39522688›Full record

ArticleJournal of advanced research2025

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.

Abbas F Almulla, Michael Maes, Bo Zhou, Hussein K Al-Hakeim, Aristo Vojdani

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Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  6. Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Abbas F AlmullaSichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand; Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
Michael MaesSichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand; Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; Research Center, Medical University of Plovdiv, Plovdiv, Bulgaria; Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. Electronic address: dr.michaelmaes@hotmail.com.
Bo ZhouDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand; Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
Hussein K Al-HakeimDepartment of Chemistry, College of Science, University of Kufa, Kufa, Iraq.
Aristo VojdaniImmunosciences Lab, Inc., Los Angeles, CA 90035, USA; Cyrex Laboratories, LLC, Phoenix, AZ 85034, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAutoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

objectivesTo examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α + β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B.

methodsIgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof.

resultsLong COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7 % of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r = 0.801.

conclusionBrain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.

Indexed as

Affective SymptomsAutoimmunityBrainCOVID-19Fatigue Syndrome, ChronicAdultAutoantibodiesFemaleHumansImmunoglobulin AImmunoglobulin GMaleMiddle AgedSARS-CoV-2AutoantibodiesImmunoglobulin AImmunoglobulin GAffective disordersChronic fatigue syndromeDepressionLong COVIDNeuroimmuneOxidative stress

Identifiers

PMID39522688
PMCPMC12789828

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.