Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles

While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the sta...

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Main Authors: Martin Tobi, Diptaraj Chaudhari, Elizabeth P. Ryan, Noreen F. Rossi, Orena Koka, Bridget Baxter, Madison Tipton, Taru S. Dutt, Yosef Tobi, Benita McVicker, Mariana Angoa-Perez
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Language:English
Published: MDPI AG 2025-06-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/7/928
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author Martin Tobi
Diptaraj Chaudhari
Elizabeth P. Ryan
Noreen F. Rossi
Orena Koka
Bridget Baxter
Madison Tipton
Taru S. Dutt
Yosef Tobi
Benita McVicker
Mariana Angoa-Perez
author_facet Martin Tobi
Diptaraj Chaudhari
Elizabeth P. Ryan
Noreen F. Rossi
Orena Koka
Bridget Baxter
Madison Tipton
Taru S. Dutt
Yosef Tobi
Benita McVicker
Mariana Angoa-Perez
author_sort Martin Tobi
collection DOAJ
description While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual <i>Bacillota</i> and <i>Bacteroidota</i> species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (<i>p</i> < 0.02); IL10 versus IL-12p70a (<i>p</i> < 0.02); IL-1b versus IL-6 (<i>p</i> < 0.01); MCP1 versus TARC (<i>p</i> < 0.03); IL-8 versus TARC (<i>p</i> < 0.002); and Eotaxin3 versus TARC (<i>p</i> < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (<i>p</i> < 0.01); TNF-α versus IL-1-β (<i>p</i> < 0.06); MCP4 versus TARC (<i>p</i> < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology.
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spelling doaj-art-e86f4750931242e69fc7b6fc5760c2fa2025-08-20T03:32:12ZengMDPI AGBiomolecules2218-273X2025-06-0115792810.3390/biom15070928Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine ProfilesMartin Tobi0Diptaraj Chaudhari1Elizabeth P. Ryan2Noreen F. Rossi3Orena Koka4Bridget Baxter5Madison Tipton6Taru S. Dutt7Yosef Tobi8Benita McVicker9Mariana Angoa-Perez10R&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USADepartment of Physiology, Wayne State University School of Medicine, Detroit, MI 48301, USADepartment of Environmental and Radiological Health Sciences, School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USAR&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USADepartment of Physiology, Wayne State University School of Medicine, Detroit, MI 48301, USADepartment of Environmental and Radiological Health Sciences, School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Environmental and Radiological Health Sciences, School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Environmental and Radiological Health Sciences, School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USAR&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USADepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68005, USAR&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USAWhile there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual <i>Bacillota</i> and <i>Bacteroidota</i> species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (<i>p</i> < 0.02); IL10 versus IL-12p70a (<i>p</i> < 0.02); IL-1b versus IL-6 (<i>p</i> < 0.01); MCP1 versus TARC (<i>p</i> < 0.03); IL-8 versus TARC (<i>p</i> < 0.002); and Eotaxin3 versus TARC (<i>p</i> < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (<i>p</i> < 0.01); TNF-α versus IL-1-β (<i>p</i> < 0.06); MCP4 versus TARC (<i>p</i> < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology.https://www.mdpi.com/2218-273X/15/7/928COVID-19Long COVIDPASC (Post Acute Sequelae of SARS-CoV-2 infection) or post-acute sequelae of COVID-19stool microbiomecytokinesp87
spellingShingle Martin Tobi
Diptaraj Chaudhari
Elizabeth P. Ryan
Noreen F. Rossi
Orena Koka
Bridget Baxter
Madison Tipton
Taru S. Dutt
Yosef Tobi
Benita McVicker
Mariana Angoa-Perez
Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
Biomolecules
COVID-19
Long COVID
PASC (Post Acute Sequelae of SARS-CoV-2 infection) or post-acute sequelae of COVID-19
stool microbiome
cytokines
p87
title Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
title_full Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
title_fullStr Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
title_full_unstemmed Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
title_short Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles
title_sort immune signatures in post acute sequelae of covid 19 pasc and myalgia chronic fatigue syndrome me cfs insights from the fecal microbiome and serum cytokine profiles
topic COVID-19
Long COVID
PASC (Post Acute Sequelae of SARS-CoV-2 infection) or post-acute sequelae of COVID-19
stool microbiome
cytokines
p87
url https://www.mdpi.com/2218-273X/15/7/928
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