Tag: IL-10

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)

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)

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment

Abstract:

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.

To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment.

Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected).

Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNg, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.

We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

Source: Bianca Besteher, Tonia Rocktaeschel, Alejandra Patricia Garza, Marlene Machnik, Johanna Ballez, Dario Lucas Helbing, Katrhin Finke, Philipp Reuken, Daniel Guellmar, Christian Gaser, Martin Walter, Nils Opel, Ildiko Rita Dunay. Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment. medRxiv 2023.07.21.23292988; doi: https://doi.org/10.1101/2023.07.21.23292988 https://www.medrxiv.org/content/10.1101/2023.07.21.23292988v1v (Full text available as PDF file)

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn’t alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic.

Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging.

It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed.

With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected.

In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered.

The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Source: Li BB, Feng CW, Qu YY, Sun ZR, Chen T, Wang YL, Wang QY, Lu J, Shao YY, Yang TS. Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome. World J Acupunct Moxibustion.  doi: 10.1016/j.wjam.2023.03.002 [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061266/ (Full text)

Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Elevation of FABP2, a marker of intestinal cell damage in ME/CFS.
  • Absence of optimal acute-phase LBP and sCD14 anti-microbial responses in ME/CFS.
  • Compensatory but inadequate B cell response to microbial translocation in ME/CFS.
  • Enhanced IL-10 regulatory response may drive the observed immunosuppression.
  • Glucose and citrate metabolic dysfunction in ME/CFS may link the IL-10 activation and suppressed anti-microbial responses.

Abstract:

The etiology and mechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are poorly understood and no biomarkers have been established. Specifically, the relationship between the immunologic, metabolic, and gastrointestinal abnormalities associated with ME/CFS and their relevance to established symptoms of the condition remain unclear.

Relying on data from two independent cohorts of ME/CFS and control study participants, one at rest and one undergoing an exercise challenge, we identify a state of suppressed acute-phase innate immune response to microbial translocation in conjunction with a compromised gut epithelium. This immunosuppression, along with observed enhancement of compensatory antibody responses to counter the microbial translocation, was associated with and may be mediated by alterations in glucose and citrate metabolism and an IL-10 immunoregulatory response. Our findings provide novel insights into mechanistic pathways, biomarkers, and potential therapeutic targets in ME/CFS, including in the context of exertion, with relevance to both intestinal and extra-intestinal symptoms.

Source: Melanie Uhde, Alyssa C. Indart, Peter H.R. Green, Robert H. Yolken, Dane B. Cook, Sanjay K. Shukla, Suzanne D. Vernon, Armin Alaedini.
Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome. Brain, Behavior, & Immunity – Health, 2023, 100627. ISSN 2666-3546, https://doi.org/10.1016/j.bbih.2023.100627.
https://www.sciencedirect.com/science/article/pii/S2666354623000418 (Full text)

High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients

Abstract:

Background: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19.

Methods: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis.

Results: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)–categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation.

Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals.

Conclusion: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.

Source: Gomes SMR, Brito ACdS, Manfro WFP, Ribeiro-Alves M, Ribeiro RSdA, da Cal MS, et al. (2023) High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients. PLoS ONE 18(4): e0283983. https://doi.org/10.1371/journal.pone.0283983 (Full text)

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

Abstract:

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease.
Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease’s poor prognosis.
Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs’ phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta.
Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.
Source: Dhawan M, Rabaan AA, Alwarthan S, Alhajri M, Halwani MA, Alshengeti A, Najim MA, Alwashmi ASS, Alshehri AA, Alshamrani SA, AlShehail BM, Garout M, Al-Abdulhadi S, Al-Ahmed SH, Thakur N, Verma G. Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID. Vaccines. 2023; 11(3):699. https://doi.org/10.3390/vaccines11030699 https://www.mdpi.com/2076-393X/11/3/699 (Full text)

The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS.

Methods: 200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines.

Results: HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients. Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active-45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively. ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS.

Conclusions: Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity.

Source: Rasa-Dzelzkaleja S, Krumina A, Capenko S, Nora-Krukle Z, Gravelsina S, Vilmane A, Ievina L, Shoenfeld Y, Murovska M; VirA project. The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2023 Jan 18;21(1):33. doi: 10.1186/s12967-023-03887-0. PMID: 36653846. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03887-0 (Full text)

Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome

Abstract:

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort.

A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome).

In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05).

Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Source: Queiroz MAF, Neves PFMD, Lima SS, Lopes JDC, Torres MKDS, Vallinoto IMVC, Bichara CDA, Dos Santos EF, de Brito MTFM, da Silva ALS, Leite MM, da Costa FP, Viana MNDSA, Rodrigues FBB, de Sarges KML, Cantanhede MHD, da Silva R, Bichara CNC, van den Berg AVS, Veríssimo AOL, Carvalho MDS, Henriques DF, Dos Santos CP, Nunes JAL, Costa IB, Viana GMR, Carneiro FRO, Palacios VRDCM, Quaresma JAS, Brasil-Costa I, Dos Santos EJM, Falcão LFM, Vallinoto ACR. Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome. Front Cell Infect Microbiol. 2022 Jun 30;12:922422. doi: 10.3389/fcimb.2022.922422. PMID: 35846757; PMCID: PMC9279918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279918/ (Full text)

Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls

Abstract:

PURPOSE: The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms.

MATERIALS AND METHODS: Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study. Plasma was analysed by ELISA for levels of the cytokines TNF-α, IL-4, IL-6 and IL-10. Participants also answered questionnaires regarding health in general, and psychiatric symptoms in detail.

RESULTS: Increased plasma levels of TNF-α in CFS/ME patients almost reached significance compared to healthy controls (p = .056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-α and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-α and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together).

CONCLUSIONS: These findings indicate that immune activity in CFS/ME patients deviates from that of healthy controls, which implies potential pathogenic mechanisms and possible therapeutic approaches to CFS/ME. More comprehensive studies should be carried out on defined CFS/ME subgroups.

Source: Groven N, Fors EA, Iversen VC, White LR, Reitan SK. Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls. Nord J Psychiatry. 2018 Jul 31:1-5. doi: 10.1080/08039488.2018.1493747. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30063870