From HHV-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID. DOI
Michaël Maes, Abbas F. Almulla,

Xiaoou Tang

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 30, 2024

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

Language: Английский

Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 103 studies comprising 58 cytokines/chemokines/growth factors DOI
Abbas F. Almulla,

Yanin Thipakorn,

Bo Zhou

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 122, P. 75 - 94

Published: Aug. 9, 2024

Language: Английский

Citations

4
Autoimmune responses to myelin-associated proteins as diagnostic and prognostic biomarkers of relapsing-remitting multiple sclerosis: Associations with human herpesvirus-6 and Epstein-Barr virus reactivation DOI Creative Commons
Aristo Vojdani, Abbas F. Almulla, Elroy Vojdani

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

The pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is linked to autoimmune attacks against myelin proteins, and reactivation Epstein-Barr virus (EBV) human herpesvirus 6 (HHV-6). However, the connection between viral biomarkers has remained unclear. To investigate immunoglobulin (Ig)G/IgA/IgM responses targeting myelin-related proteins in association with EBV HHV-6 replication markers RRMS. We recruited 55 patients RRMS 63 healthy controls assessed IgG/IgA/IgM seven components, as well nuclear antigen 1 (EBNA-1) deoxyuridine-triphosphate nucleotidohydrolase (dUTPases). Disability was evaluated using Expanded Status Scale (EDSS) disease progression Multiple Sclerosis Severity Score (MSSS). levels were significantly higher than controls. IgG basic protein (MBP) (IgG-MBP), IgM-myelin-associated glycoprotein (IgM-MAG)-37-60, IgA-MBP, IgA-myelin-oligodendrocyte-glycoprotein (IgA-MOG-31-55) distinguished from a predictive accuracy 96.6 % (sensitivity = 95.7 %, specificity 95.2 %) an area under ROC curve 0.991. A large part variance EDSS (around 75 MSSS score (62.8 explained by IgG-MBP, IgM-MBP, IgA-MOG-31-55, IgM-MAG. Part (47.4 immune EBNA dUTPases HHV-6. Autoimmune reactivities are valuable severity Reactivation may trigger or maintain these thereby impacting progression.

Language: Английский

Citations

0
From human herpes virus‐6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID DOI Creative Commons
Michael Maes, Abbas F. Almulla,

Xiaoou Tang

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(8)

Published: Aug. 1, 2024

Inflammation and autoimmune responses contribute to the pathophysiology of Long COVID, its affective chronic fatigue syndrome symptoms, labeled "the physio-affective phenome." To investigate whether COVID phenome are linked autoimmunity tight junction proteins, zonulin occludin (ZOOC), immune reactivity lipopolysaccharides (LPS), latter associated with signs human herpes virus-6 (HHV-6) reactivation, directed against oligodendrocyte neuronal including myelin basic protein. IgA/IgM/IgG severe acute respiratory coronavirus 2 (SARS-CoV-2), HHV-6, ZOOC, C-reactive protein (CRP), advanced oxidation products (AOPPs), were measured in 90 patients healthy controls. The was conceptualized as a factor extracted from physical symptom domains. Neural network identified IgA LPS (IgA-LPS), IgG-ZOOC, IgG-LPS, IgA-ZOOC important variables diagnosis an area under ROC curve 0.755. Partial Least Squares analysis showed that 40.9% variance explained by CRP, IgA-myelin (MBP), IgG-MBP. A large part variances both MBP (36.3%-39.7%) (IgA IgG) ZOOC. strongly indicants HHV-6 which turn increased IgM-SARS-CoV-2. Autoimmunity components junctions bacterial translocation may be involved COVID's phenome.

Language: Английский

Citations

3
Reactivation of Human Herpesvirus 6 and Epstein-Barr Virus in relapsing remitting multiple sclerosis: association with disabilities, disease progression, and inflammatory processes. DOI Creative Commons
Abbas F. Almulla, Aristo Vojdani, Yingqian Zhang

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS). Reactivation of Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) observed in MS. Objectives This study investigates immunoglobulins (Ig)G, IgM, IgA directed against EBV nuclear antigen EBNA-366-406, HHV-6 deoxyuridine-triphosphatase (dUTPase), different immune profiles 58 patients with relapsing remitting MS (RRMS) compared to 60 healthy controls. Methods We employed enzyme-linked immunosorbent assays (ELISA) measure viral antigens. Multiplex immunoassays were used cytokines, chemokines growth factor levels that compute profiles, including M1 macrophage, T helper (Th)-1, Th-17, overall activation. assessed disabilities using Expanded Disability Status Scale (EDSS) disease progression Sclerosis Severity Score (MSSS). Results IgG/IgA/IgM three antigens significantly higher RRMS than was discriminated from controls by IgG IgM dUTPase, yielding an accuracy 91.5% (sensitivity=87.3% specificity=95.2%). Neural network analysis showed EBV-dUTPase, yielded area under ROC curve 1 predictive 97.1%. There strong associations between IgG/IgM responses EBV-dUTPases EDSS/MSSS scores aberrations M1, Conclusions reactivation play key role these effects are mediated activation cytokine profiles.

Language: Английский

Citations

3
Long COVID outcomes following omicron wave in non-hospital population DOI Creative Commons

Wang Ruiyin,

Qi Jia, Tingting Wang

et al.

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: March 15, 2024

Background The persistence of symptoms or the development new following a diagnosis SARS-CoV-2 has given rise to multifaceted clinical condition referred as “long COVID” (LC). understanding LC among China’s non-hospitalized population continues be insufficient. This investigation was designed evaluate protracted consequences amongst this demographic, well identify associated risk factors. Methods research constitutes prospective cohort study focusing on individuals, aged between 18 and 59, who have been positively diagnosed with COVID-19. Each participant subjected sequence questionnaire-based surveys, status depression anxiety. A logistic regression model, adjusted for multiple variables, employed scrutinize correlation demographic elements, lifestyle attributes, health-related factors in relation conditions post COVID-19 infection. Results total 706 individuals participated 3 months follow-up, 620 continuing 6 follow-up. median age 35 (28, 43) years, 597 (85%) are female. Upon Compared patients without LC, higher proportion females (420 (87%) vs. 177 (79%); p = 0.010), were older (35 (29, 44) years 33 (27, 41) years; 0.010) more comorbidities. Out all participants, 483 (68.4%) reported experiencing at least one symptom mark, while 49.7% persisting mark. At most prevalent persistent cough (46%), fatigue (38%), shortness breath (34%). By (25%), (22%), sleep disorders (16%) commonly symptoms. Anxiety consistently throughout follow-up period. Most patient fade over time, quickest decreases observed (from 46 9%), expectoration 26 6.3%), smell disorder 16 3.9%), taste 3.5%). Male those possessing advanced educational qualifications exhibit decreased susceptibility sustained incidence coughing. Conversely, presence comorbidities identified breath. Conclusion In after COVID-19, it that majority tend decrease time. primary residual noticed month fatigue, dyspnea, disturbances. However, it’s noteworthy these subtle variations. Furthermore, psychological sequelae, namely anxiety, frequently survivors.

Language: Английский

Citations

2
Chronic fatigue syndrome, depression, and anxiety symptoms due to relapsing-remitting multiple sclerosis are associated with reactivation of Epstein-Barr virus and Human Herpesvirus 6. DOI Creative Commons
Michaël Maes, Abbas F. Almulla, Elroy Vojdani

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Relapsing-remitting multiple sclerosis (RRMS) is defined by elevated IgG/IgA/IgM responses targeting Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA) and deoxyuridine-triphosphatases (dUTPases) of Human herpsesvirus-6 (HHV-6) EBV. These suggest that the viruses are being replicated reactivated. An increased prevalence chronic fatigue syndrome, depression, anxiety associated with signs immune activation in RRMS. Nevertheless, there a lack data regarding association between viral reactivation neuropsychiatric symptoms This study investigated to EBNA, EBV HHV-6-dUTPases, 58 remitted RRMS patients 63 normal controls. The McDonald criteria were employed establish diagnosis MS. Expanded Disability Status Scale (EDSS) Multiple Sclerosis Severity Score evaluate disabilities caused We evaluated scores Hamilton Depression (HAMD) Anxiety (HAMA) Rating Scales, Fibro-Fatigue (FF) scale. One latent construct was extracted from EDSS, MSSS, FF, HAMD, HAMA scores. discovered combined effects IgG IgM-HHV-6-dUTPAses accounted for 63.7% variance this construct. Furthermore, total HAMA, HAMD substantially IgM-HHV-6-dUTPAses, accounting approximately 38.7% 51.0% variance. three rating scale also significantly correlated IgA reactivity directed both dUTPases EBNA. In conclusion, replication HHV-6 contributes as well depression due

Language: Английский

Citations

2
The tryptophan catabolite or kynurenine pathway in Long COVID disease: A systematic review and meta-analysis DOI
Abbas F. Almulla,

Yanin Thipakorn,

Bo Zhou

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

2
Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 82 studies comprising 58 cytokines/chemokines/growth factors DOI Creative Commons
Abbas F. Almulla,

Yanin Thipakorn,

Bo Zhou

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Background Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there no comprehensive meta-analysis focusing on activation the response system (IRS) and compensatory immunoregulatory (CIRS) along other phenotypes in LC patients. Objectives This designed to explore IRS CIRS profiles patients, individual cytokines, chemokines, growth factors, C-reactive protein (CRP) immune-associated neurotoxicity. Methods To gather relevant for our research, we conducted a thorough search using databases such PubMed, Google Scholar, SciFinder, covering all available literature up December 20th, 2023. Results The current encompassed 82 examined multiple profiles, protein, 58 cytokines/chemokines/growth factors 3836 patients versus 4537 normal controls (NC). showed significant increases IRS/CIRS ratio (standardized mean difference (SMD:0.156, confidence interval (CI): 0.051;0.261), (SMD: 0.345, CI: 0.222;0.468), M1 macrophage 0.421, 0.290;0.551), T helper (Th)1 0.353, 0.189;0.517), Th17 0.492, 0.332;0.651) neurotoxicity 0.327 0.205;0.448). In addition, CRP 19 different cytokines displayed significantly compared NC. Conclusion characterized increased

Language: Английский

Citations

1
Editorial: Neuropsychiatric and neurodegenerative aspects of acute and long COVID DOI Creative Commons
Abbas F. Almulla, Hussein Kadhem Al‐Hakeim

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Dec. 12, 2023

EDITORIAL article Front. Mol. Neurosci., 12 December 2023Sec. Brain Disease Mechanisms Volume 16 - 2023 | https://doi.org/10.3389/fnmol.2023.1343930

Language: Английский

Citations

2
The tryptophan catabolite or kynurenine pathway in Long COVID disease: A systematic review and meta-analysis DOI
Abbas F. Almulla,

Yanin Thipakorn,

Bo Zhou

et al.

Published: May 1, 2024

Abstract Background Recent studies confirm the involvement of activated immune-inflammatory responses and increased oxidative nitrosative stress in Long COVID (LC) disease. However, influence these pathways on metabolism tryptophan (TRP) through TRP catabolite (TRYCAT) pathway their mediating effects LC pathophysiology, has not been fully explored. Objective This meta-analysis investigates peripheral TRYCAT levels patients with Method review utilized systematic searches PubMed, Google Scholar, SciFinder, including 14 full-text articles 1,167 participants, consisting 480 687 normal controls. Results The results indicated a significant increase kynurenine (KYN)/TRP ratio, large effect size (standardized mean difference, SMD = 0.755; confidence intervals, CI: 0.119;1.392), compared to Additionally, exhibited decrease (SMD -0.520, -0.793; -0.246) an KYN after imputing missing 1.176, 0.474; 1.877), suggesting activation Indoleamine 2,3-dioxygenase (IDO) enzyme upregulation pathway. No elevation TRYCAT-related neurotoxicity, kynurenic acid (KA)/KYN 3-hydroxykynurenine (3-HK)/KYN ratios were observed Conclusion current findings indicate that pathway, characterized by decreased maybe elevated levels, plays role pathophysiology LC.

Language: Английский

Citations

0