Tag: long Covid

Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome

Abstract:

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs).

Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC.

While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations.

Source: Bizjak DA, Ohmayer B, Buhl JL, Schneider EM, Walther P, Calzia E, Jerg A, Matits L, Steinacker JM. Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome. Int J Mol Sci. 2024 Jan 30;25(3):1675. doi: 10.3390/ijms25031675. PMID: 38338957; PMCID: PMC10855807. https://pmc.ncbi.nlm.nih.gov/articles/PMC10855807/ (Full text)

Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning. Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection.

Expression of the toxic human endogenous retrovirus (HERV)-W ENV protein can be induced by viral infection and HERV-W detection was correlated with acute COVID-19 severity and found significantly expressed in post-COVID-19 condition. This study shows that HERV-W ENV may also be present in prepandemic cases of ME/CFS, FM or co-diagnosed with both clinical criteria, suggesting viral participation in these chronic diseases.

To learn whether associated antiviral mechanisms may also show differing patterns of immunological responses, we measured IgM, IgG, IgA and IgE antibody isotypes against SARS-CoV-2 spike and nucleocapsid antigens, the levels of IL-6, IL-8, IL-10, IFNγ and TNFα cytokines, the level of NfL, a neural damage biomarker, as well as some blood cell markers potentially related with fatigue.

Importantly, some of the measured variables showed a capacity to discriminate post-COVID-19 condition cases from all other participants, with 100 % sensitivity and up to 71.9 % specificity providing a new tool for a differential diagnosis between diseases or syndromes with so many overlapping clinical symptoms. Interestingly, the detected markers showed moderate-to-strong correlations with patient symptoms pointing at novel therapeutic opportunities.

Source: Giménez-Orenga K, Pierquin J, Brunel J, Charvet B, Martín-Martínez E, Lemarinier M, Fried S, Lucas A, Perron H, Oltra E. Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia. Brain Behav Immun Health. 2025 Jul 4;48:101058. doi: 10.1016/j.bbih.2025.101058. PMID: 40726775; PMCID: PMC12302357. https://pmc.ncbi.nlm.nih.gov/articles/PMC12302357/ (Full text)

Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients

Abstract:

Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC).

Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation.

A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort.

Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.

Source: Peppercorn K, Sharma S, Edgar CD, Stockwell PA, Rodger EJ, Chatterjee A, Tate WP. Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients. Int J Mol Sci. 2025 Jul 10;26(14):6631. doi: 10.3390/ijms26146631. PMID: 40724879. https://www.mdpi.com/1422-0067/26/14/6631 (Full text)

Growing recognition of post-acute infection syndromes

Commentary:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID affect large numbers of people, and constitute a substantial burden to the U.S. and global economies. The article by Eckey et al., in this issue of PNAS (1), adds to the growing evidence that the two illnesses have much in common. Moreover, the illnesses may represent just two examples of an even larger, recently recognized class of illness: post-acute infection syndromes (PAIS) (2).
ME/CFS
This illness first attracted attention in the 1980s. Typically, people suffering from ME/CFS previously have been healthy, and then develop a flu-like illness. While that illness appears initially not unlike previous transient illnesses, and while the respiratory symptoms and fever usually improve, people are left with a severe, persisting fatigue, cognitive problems, worsened symptoms following physical or mental exertion or upright posture, as well as unrefreshing sleep, an illness that can last for years (3, 4). The symptoms are not relieved by rest, and greatly impair a person’s ability to function at work and at home. Some individuals are homebound, some largely bedbound. People with ME/CFS often say, in so many words, “I am no longer the person I was.”
In the 1980s, some scientists suspected that a novel human pathogen was causing the illness. Such speculation seemed reasonable, since a novel virus recently had been discovered to cause the AIDS. However, no single, novel pathogen has emerged as the cause of ME/CFS.
Moreover, the standard laboratory tests that were performed in the 1980s generally came back “normal,” leading some to believe there were no underlying biological abnormalities to explain the symptoms. However, over the past 40 y, thousands of studies have identified many underlying abnormalities involving the brain, immune system, energy metabolism, redox imbalance, vascular injury, and gut microbiota (4–9). The symptoms of the illness are, indeed, accompanied by objective abnormalities.
Despite the fact that—in the United States, alone—the illness is estimated to affect up to 3.1 million people, and to generate direct and indirect expenses of approximately $36 to 51 billion annually (3, 10), relatively few investigators have sought to study the illness: the initial skepticism about whether the illness had a biological basis may have created a lingering stigma. That skepticism faded, to some degree, following publication in 2015 of a report from the U.S. National Academies of Science, Engineering and Medicine highlighting the importance of the problem (3).
Long COVID
Then, along came the COVID-19 pandemic. It was predicted that the pandemic would greatly increase the number of people with an ME/CFS-like illness (11), and that has proved to be the case. Many who have “recovered” from acute COVID-19, even from mild cases, have developed a persisting illness (called “long COVID”) with symptoms much like ME/CFS. The cumulative global incidence of long COVID may be as high as 400 million individuals (5, 8), and the costs to the U.S. and global economy (not including the direct costs of healthcare) may be several trillion dollars in the next 5 to 10 y (8, 12).
Comparing ME/CFS and Long COVID
The similarity of the symptoms seen in ME/CFS and long COVID is underscored by the report from Eckey et al. (1). The study involved a survey of nearly 4,000 people with these illnesses. Participants recorded the prevalence and severity of a large number of symptoms, comorbid illnesses, and responses to different treatments.
The authors recognize that such a survey has important limitations. The diagnoses of ME/CFS, long COVID, and comorbid illnesses were self-reported, and not determined by protocol-directed objective testing—although such testing often had been performed by their doctors. Likewise, the responses to different treatments were self-reported, not the results of randomized, placebo-controlled trials. Nevertheless, the large number of study subjects, and the consistency of their responses, suggests that their responses are valid.
Symptoms.
As seen in figure 1 of the report by Eckey et al. (1), the frequency of each of the symptoms is very similar in both illnesses. At the same time, there may be subgroups of people with both ME/CFS and long COVID in whom different symptoms are predominant: it is possible that these subgroups have different underlying pathophysiology, responses to treatments, and prognosis.
Underlying Pathophysiology.
Of course, the fact that the symptoms and symptom frequency are similar does not necessarily mean the two illnesses share an underlying pathophysiology. Nevertheless, it appears that they do. A detailed analysis of the underlying biological abnormalities seen in both illnesses reveals a striking similarity (6).
Comorbid Diseases.
The survey conducted by Eckey et al., addressed two other dimensions by which to compare the two illnesses. First, the survey found that people with the two illnesses frequently had the same comorbid conditions, particularly postural orthostatic tachycardia syndrome (POTS), migraine, dysautonomia, anxiety and depression, mast cell activation syndrome (MCAS), Ehlers–Danlos syndrome (EDS)/joint hypermobility, and attention deficit disorder (ADD) (1).

Response to Therapies.

Patients with the two illnesses also responded similarly to specific treatments. Remarkably, even at the level of specific symptoms, responses were similar in people with the two illnesses, and the drugs most effective against particular symptoms would be expected to improve those symptoms, adding credibility to the self-reported improvement (1). Thus, the study is consistent with others in finding similar symptoms in people with the two illnesses and, additionally, finds similar comorbidities and responses to treatment.

PAIS

ME/CFS and long COVID are not the only two illnesses that share very similar symptoms. Over the past century, there have been many reports of an illness with very similar symptoms following multiple different acute bacterial, viral, fungal, and protozoal infections; hence, the proposal to call all of these illnesses PAIS (2). Long COVID surely is a PAIS (since the inciting infectious agent is known), and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) likely often is (even though the inciting agents often have not been pursued by physicians).

IACIs
PAIS, in turn, are one example of an even larger umbrella category, a group of disorders called IACIs (9, 13). As shown in Fig. 1, we distinguish three categories of IACIs: new organ injury from an infectious agent, such as the development of multiple sclerosis following primary infection with Epstein–Barr virus or duodenal ulcers caused by Helicobacter pylori; accelerated incidence of disease processes that had not yet become apparent before the time of an acute infection (including accelerated atherosclerosis and neurodegeneration post-COVID) (8, 14); and PAIS. Some observers use the term long COVID to include all three categories of illness following acute infection with SARS-CoV-2. We restrict the use of the term long COVID to just the PAIS that can follow SARS-CoV-2 infection.
Read the rest of this article here: https://www.pnas.org/doi/10.1073/pnas.2513877122
Source: A.L. Komaroff, Growing recognition of post-acute infection syndromes, Proc. Natl. Acad. Sci. U.S.A. 122 (29) e2513877122, https://doi.org/10.1073/pnas.2513877122 (2025). https://www.pnas.org/doi/10.1073/pnas.2513877122 (Full text)

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

Abstract:

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis.

In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

Source: Paroli M, Gioia C, Accapezzato D, Caccavale R. Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review. Int J Mol Sci. 2024 May 29;25(11):5922. doi: 10.3390/ijms25115922. PMID: 38892110; PMCID: PMC11172859. https://pmc.ncbi.nlm.nih.gov/articles/PMC11172859/ (Full text)

Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19

Abstract:

Background/aims: Post-acute sequelae of COVID-19 (PASC) are highly heterogeneous; therefore, the pathophysiological mechanisms for PASC remain unclear. In this study, we aimed to examine the immunologic aspects of various PASC symptoms.

Methods: We prospectively enrolled adults aged ≥ 18 years who were diagnosed with COVID-19 between August 2022 and September 2023. Blood samples were collected from all participants, who were interviewed using a questionnaire for PASC symptoms at least once between 1 and 6 months after the COVID-19 diagnosis. For immunological evaluation, plasma concentrations of SARS-CoV-2 spike subunit 1-specific IgG and 33 cytokines were measured using enzyme-linked immunosorbent assays and multiplex-based immunoassay, respectively.

Results: In total, 156 pairs of blood samples and symptom reports from 79 participants were eligible for analysis. The most frequent symptom was fatigue, followed by post exertional malaise, chronic cough, thirst, and brain fog. Gastrointestinal symptoms, chest pain, post exertional malaise, smell/taste change, fatigue, brain fog, abnormal movement, and palpitation were accompanied by significant increases in IL-10, VEGF, and inflammatory cytokines like MIP-1α, IL-1β, IL-6, IL-8, MIG, granzyme A, and CX3CL1 levels, while chronic cough, dizziness, dyspnea, and hair loss were not accompanied by significant differences in cytokine levels.

Conclusion: Symptoms classified into different categories based on the dysfunctional organs may share a common pathophysiology regarding elevation of certain cytokines. Although PASC symptoms are heterogeneous, our findings suggest that T-cell recruitment, thrombosis, and increased vascular permeability might contribute to various symptom clusters sharing common pathophysiological mechanisms.

Source: Kwon JS, Chang E, Jang HM, Kim JY, Kim W, Son JY, Cha J, Jang CY, Bae S, Jung J, Kim MJ, Chong YP, Lee SO, Choi SH, Kim YS, Kim SH. Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19. Korean J Intern Med. 2025 Jul;40(4):667-675. doi: 10.3904/kjim.2024.217. Epub 2025 Jul 1. PMID: 40635493. https://kjim.org/journal/view.php?doi=10.3904/kjim.2024.217 (Full text)

Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study

Abstract:

Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other poorly understood post-acute infection syndromes (PAIS) can present with unexplained symptoms or conditions that may be misunderstood by healthcare providers, causing delays in diagnosis and care. To address these issues, the Centers for Disease Control and Prevention (CDC) funded the Long COVID and Fatiguing Illness Recovery Program (LC&FIRP), initiated as a pilot project to assess whether providing tele-mentoring and other online education for primary care providers could help them improve the quality of life and support the recovery of their patients with these conditions.

The LC&FIRP multi-disciplinary team-based care approach is built on the Extension for Community Healthcare Outcomes (ECHO) learning model, which is an evidence-based virtual learning framework developed by the University of New Mexico and designed to disseminate and implement best practices, especially in under-resourced areas. A distinctive feature of LC&FIRP was the inclusion of lived-experience experts. To explore the influence of lived-experience experts on the care patients received, we collected the educational recommendations provided by the lived-experience experts during webinar sessions (January 2022-March 2024) and grouped these by themes.

The major themes that emerged included validation of patients’ illness experience; attitudes and beliefs about Long COVID, ME/CFS, and PAIS; understanding patients’ challenges and communicating with empathy; navigating referrals; recognizing and supporting disability; and supporting self-care. Investigators also interviewed patients of the Family Health Centers of San Diego (FHCSD) about their experiences receiving care from participating primary care providers and employed content analysis methods to code interview transcripts to identify themes among patients’ perspectives. Positive comments from the patients about topics emphasized by the lived-experience experts provided evidence of providers’ uptake and application of the experts’ recommendations and support the value of involving lived-experience experts in medical education to improve health services.

Source: Weaver SS, Carry M, Bertolli J, Godino J, Struminger B, Taren D, Scott JD, Sharp SP, Samaniego J, Bean DR, Issa A, Lin JS, Unger ER, Ramers CB. Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study. Front Health Serv. 2025 Jun 27;5:1562651. doi: 10.3389/frhs.2025.1562651. PMID: 40656206; PMCID: PMC12245761. https://pmc.ncbi.nlm.nih.gov/articles/PMC12245761/ (Full text)

Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health

Abstract:

Background: Long-COVID refers to ongoing, relapsing, or new symptoms present 30 or more days after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study examined the prevalence and severity of neurologic symptoms at greater than 1 month following acute SARS-CoV-2 infection and the influence of pre-existing neurologic and psychiatric conditions, current depression and anxiety status, and hospitalization on the presence and severity of these symptoms.

Methods: This prospective cohort study recruited primarily self-referred Long-COVID participants with confirmed SARS-CoV-2 infection. Online questionnaires inquiring about pre-existing conditions, neurologic symptoms and their severity pre, during and post COVID-19, and current anxiety and depression screening were completed by 213 participants at a median time of 8 months after infection. Descriptive analyses and prevalence modeling were performed.

Results: The most frequent neurologic symptoms post COVID-19 were fatigue, concentration/memory difficulties, unrefreshed sleep, and dysarthria/word finding difficulties (73.2–86.4%). Neurologic symptoms were highly prevalent with significantly greater odds post COVID-19 compared to pre for all symptoms and higher prevalence at time periods farther from infection, including those implicit in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Several severe neurologic symptoms were significantly more prevalent post COVID-19. Moderate to severe anxiety (34%) and depression (27%) were observed post COVID-19. Preexisting neurologic or psychiatric conditions did not demonstrate any significant difference in neurologic symptom prevalence post COVID-19. Those who met criteria for moderate or severe anxiety post COVID-19 had a significant difference in prevalence of fatigue, sensitivity to touch and unrefreshed sleep. Similarly, fatigue, concentration/memory difficulty and unrefreshed sleep were more prevalent in moderate to severe depression. There were no significant differences in neurologic symptom prevalence in a hospitalized group when compared to non- hospitalized.

Conclusion: Long-COVID has a high burden of long lasting and severe neurological sequelae. These sequelae are independent of pre-existing self-reported neurologic and psychiatric conditions, as well as previous hospitalization. Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19. Focus on the biological impact of SARS-CoV-2 on the nervous system will be essential in ameliorating the tremendous symptom burden left in the wake of the COVID-19 pandemic.

Source: Huff Hanalise V. , Roberts Henry , Bartrum Elizabeth , Norato Gina , Grayson Nicholas , Fleig Katherine , Wilkerson Miciah J. , Stussman Barbara J. , Nath Avindra , Walitt Brian. Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health. Frontiers in Neurology, Volume 16 – 2025 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1562084 10.3389/fneur.2025.1562084 ISSN:1664-2295 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1562084/full (Full text)

Two Neurocognitive Domains Identified for Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of COVID-19

Abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of COVID-19 (PASC) often have neurocognitive complaints that involve memory and concentration problems and difficulties paying attention. Other neurocognitive domains such as hypersensitivity to noise and light have rarely been included as aspects of neurocognitive impairment for these post-viral conditions.

The current study evaluated a more extensive list of neurocognitive items for a group of 2,313 patients with ME/CFS and 299 patients with PASC. Exploratory factor analyses found two factors for each patient group, one involving classic memory and concentration symptoms and the other involving sensory overload phenomena. The findings suggest that researchers might consider expanding the types of self-report neurocognitive symptoms among patients with these post-viral illnesses.

Source: Ariadna E Sandoval, Mingqi Li, Leonard A. Jason. Two Neurocognitive Domains Identified for Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of COVID-19. Front. Neurol., Sec. Cognitive and Behavioral Neurology, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1612548 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1612548/abstract

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

Abstract:

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 Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p < 0.02); IL10 versus IL-12p70a (p < 0.02); IL-1b versus IL-6 (p < 0.01); MCP1 versus TARC (p < 0.03); IL-8 versus TARC (p < 0.002); and Eotaxin3 versus TARC (p < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (p < 0.01); TNF-α versus IL-1-β (p < 0.06); MCP4 versus TARC (p < 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.
Source: Tobi, M., Chaudhari, D., Ryan, E. P., Rossi, N. F., Koka, O., Baxter, B., Tipton, M., Dutt, T. S., Tobi, Y., McVicker, B., & Angoa-Perez, M. (2025). 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, 15(7), 928. https://doi.org/10.3390/biom15070928 https://www.mdpi.com/2218-273X/15/7/928 (Full text)