Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study

Abstract Background Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association wit...

Full description

Bibliographic Details
Main Authors: Joan Carles Domingo, Federica Battistini, Begoña Cordobilla, Maria Cleofé Zaragozá, Ramón Sanmartin-Sentañes, Jose Alegre-Martin, Trinitat Cambras, Jesus Castro-Marrero
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-024-05148-0
_version_ 1827284103101153280
author Joan Carles Domingo
Federica Battistini
Begoña Cordobilla
Maria Cleofé Zaragozá
Ramón Sanmartin-Sentañes
Jose Alegre-Martin
Trinitat Cambras
Jesus Castro-Marrero
author_facet Joan Carles Domingo
Federica Battistini
Begoña Cordobilla
Maria Cleofé Zaragozá
Ramón Sanmartin-Sentañes
Jose Alegre-Martin
Trinitat Cambras
Jesus Castro-Marrero
author_sort Joan Carles Domingo
collection DOAJ
description Abstract Background Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. Methods This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. Results Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2 - + NO3 -) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1β (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. Conclusions Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.
first_indexed 2024-04-24T09:48:44Z
format Article
id doaj.art-74b49f3d59be4ab481aedd0488faca50
institution Directory Open Access Journal
issn 1479-5876
language English
last_indexed 2024-04-24T09:48:44Z
publishDate 2024-04-01
publisher BMC
record_format Article
series Journal of Translational Medicine
spelling doaj.art-74b49f3d59be4ab481aedd0488faca502024-04-14T11:27:47ZengBMCJournal of Translational Medicine1479-58762024-04-0122111910.1186/s12967-024-05148-0Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort studyJoan Carles Domingo0Federica Battistini1Begoña Cordobilla2Maria Cleofé Zaragozá3Ramón Sanmartin-Sentañes4Jose Alegre-Martin5Trinitat Cambras6Jesus Castro-Marrero7Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of BarcelonaMolecular Modelling and Bioinformatics Group, Institute for Research in Biomedicine, Barcelona Institute of Science and TechnologyDepartment of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of BarcelonaClinical Research Department, Laboratorios ViñasDivision of Rheumatology, Clinical Unit in ME/CFS and Long COVID, Vall d’Hebron University Hospital, Universitat Autònoma de BarcelonaDivision of Rheumatology, Clinical Unit in ME/CFS and Long COVID, Vall d’Hebron University Hospital, Universitat Autònoma de BarcelonaDepartment of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of BarcelonaDivision of Rheumatology, Research Unit in ME/CFS and Long COVID, Vall d’Hebron Research Institute, Universitat Autònoma de BarcelonaAbstract Background Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. Methods This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. Results Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2 - + NO3 -) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1β (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. Conclusions Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.https://doi.org/10.1186/s12967-024-05148-0BiomarkersChronic fatigue syndromeEndothelial dysfunctionInflammationLong COVIDMyalgic encephalomyelitis
spellingShingle Joan Carles Domingo
Federica Battistini
Begoña Cordobilla
Maria Cleofé Zaragozá
Ramón Sanmartin-Sentañes
Jose Alegre-Martin
Trinitat Cambras
Jesus Castro-Marrero
Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
Journal of Translational Medicine
Biomarkers
Chronic fatigue syndrome
Endothelial dysfunction
Inflammation
Long COVID
Myalgic encephalomyelitis
title Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
title_full Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
title_fullStr Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
title_full_unstemmed Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
title_short Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study
title_sort association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis chronic fatigue syndrome and post covid 19 condition a prospective pilot cohort study
topic Biomarkers
Chronic fatigue syndrome
Endothelial dysfunction
Inflammation
Long COVID
Myalgic encephalomyelitis
url https://doi.org/10.1186/s12967-024-05148-0
work_keys_str_mv AT joancarlesdomingo associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT federicabattistini associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT begonacordobilla associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT mariacleofezaragoza associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT ramonsanmartinsentanes associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT josealegremartin associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT trinitatcambras associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy
AT jesuscastromarrero associationofcirculatingbiomarkerswithillnessseveritymeasuresdifferentiatesmyalgicencephalomyelitischronicfatiguesyndromeandpostcovid19conditionaprospectivepilotcohortstudy