Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients

Abstract Introduction Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical sympto...

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Main Authors: Chafik Tilikete, Imen Zamali, Zeineb Meddeb, Ghassen Kharroubi, Soumaya Marzouki, Tarak Dhaouadi, Ahlem Ben Hmid, Samar Samoud, Yousr Galai, Selma Charfeddine, Leila Abid, Salem Abdessalem, Jihène Bettaieb, Saloua Hamzaoui, Kamel Bouslama, Mélika Ben Ahmed
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-024-10222-5
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author Chafik Tilikete
Imen Zamali
Zeineb Meddeb
Ghassen Kharroubi
Soumaya Marzouki
Tarak Dhaouadi
Ahlem Ben Hmid
Samar Samoud
Yousr Galai
Selma Charfeddine
Leila Abid
Salem Abdessalem
Jihène Bettaieb
Saloua Hamzaoui
Kamel Bouslama
Mélika Ben Ahmed
author_facet Chafik Tilikete
Imen Zamali
Zeineb Meddeb
Ghassen Kharroubi
Soumaya Marzouki
Tarak Dhaouadi
Ahlem Ben Hmid
Samar Samoud
Yousr Galai
Selma Charfeddine
Leila Abid
Salem Abdessalem
Jihène Bettaieb
Saloua Hamzaoui
Kamel Bouslama
Mélika Ben Ahmed
author_sort Chafik Tilikete
collection DOAJ
description Abstract Introduction Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Methods Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. Results The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. Conclusion Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.
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spelling doaj-art-5635ab66ea3e4334872c4ec3ad9c68172025-08-20T02:32:55ZengBMCBMC Infectious Diseases1471-23342024-11-0124111310.1186/s12879-024-10222-5Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patientsChafik Tilikete0Imen Zamali1Zeineb Meddeb2Ghassen Kharroubi3Soumaya Marzouki4Tarak Dhaouadi5Ahlem Ben Hmid6Samar Samoud7Yousr Galai8Selma Charfeddine9Leila Abid10Salem Abdessalem11Jihène Bettaieb12Saloua Hamzaoui13Kamel Bouslama14Mélika Ben Ahmed15Faculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarDepartment of Clinical Immunology, Institut Pasteur de TunisFaculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarDepartment of Clinical Immunology, Institut Pasteur de TunisDepartment of Clinical Immunology, Institut Pasteur de TunisDepartment of Cardiology, Hedi Chaker University Hospital SfaxDepartment of Cardiology, Hedi Chaker University Hospital SfaxPasteur ClinicDepartment of Clinical Immunology, Institut Pasteur de TunisFaculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarFaculté de Médecine de Tunis, University Tunis El ManarAbstract Introduction Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Methods Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. Results The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. Conclusion Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.https://doi.org/10.1186/s12879-024-10222-5CytokinesEndothelial dysfunctionFlow cytometryPost-COVID-19 syndromeSARS-CoV-2
spellingShingle Chafik Tilikete
Imen Zamali
Zeineb Meddeb
Ghassen Kharroubi
Soumaya Marzouki
Tarak Dhaouadi
Ahlem Ben Hmid
Samar Samoud
Yousr Galai
Selma Charfeddine
Leila Abid
Salem Abdessalem
Jihène Bettaieb
Saloua Hamzaoui
Kamel Bouslama
Mélika Ben Ahmed
Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
BMC Infectious Diseases
Cytokines
Endothelial dysfunction
Flow cytometry
Post-COVID-19 syndrome
SARS-CoV-2
title Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
title_full Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
title_fullStr Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
title_full_unstemmed Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
title_short Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
title_sort exploring the landscape of symptom specific inflammatory cytokines in post covid syndrome patients
topic Cytokines
Endothelial dysfunction
Flow cytometry
Post-COVID-19 syndrome
SARS-CoV-2
url https://doi.org/10.1186/s12879-024-10222-5
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