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https://www.researchsquare.com/article/rs-3736031/v1
Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective cohort study
Joan Carles Domingo1
Federica Battistini2
Begoña Cordobilla1
Maria Cleofé Zaragozá3
Ramón Sanmartin-Sentañes4
Jose Alegre-Martin5
Trinitat Cambras6
Jesus Castro-Marrero7
ORCID
Email
1 University of Barcelona Faculty of Biology: Universitat de Barcelona Facultat de Biologia,
2 Institute for Research in Biomedicine: Institut de Recerca Biomedica,
3 Vall d'Hebron Research Institute: Vall d'Hebron Institut de Recerca,
4 Vall d’Hebron Hospital Universitari: Vall d'Hebron Hospital Universitari,
5 Vall d’Hebron Hospital Universitari: Hospital Universitari Vall d'Hebron,
6 Universitat de Barcelona Facultat de Farmacia i Ciencies de l'Alimentacio,
7 Vall d'Hebron Institut de Recerca
https://doi.org/10.21203/rs.3.rs-3736031/v1
This work is licensed under a CC BY 4.0 License
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 status.
Methods
This prospective, cross-sectional, case-control cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers to assess endothelial function and systemic inflammation. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched healthy subjects were included. Regression analysis was used to examine associations between self-reported outcome measures and circulating biomarkers in 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) with the 10-min NASA lean test. Compared with 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 control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did 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 endothelial and inflammatory biomarkers.
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.
Biomarkers
Chronic fatigue syndrome
Endothelial dysfunction
Inflammation
Long COVID
Myalgic encephalomyelitis
Post-acute sequelae of COVID-19
Post-exertional malaise
Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective cohort study
Joan Carles Domingo1
Federica Battistini2
Begoña Cordobilla1
Maria Cleofé Zaragozá3
Ramón Sanmartin-Sentañes4
Jose Alegre-Martin5
Trinitat Cambras6
Jesus Castro-Marrero7
ORCID
1 University of Barcelona Faculty of Biology: Universitat de Barcelona Facultat de Biologia,
2 Institute for Research in Biomedicine: Institut de Recerca Biomedica,
3 Vall d'Hebron Research Institute: Vall d'Hebron Institut de Recerca,
4 Vall d’Hebron Hospital Universitari: Vall d'Hebron Hospital Universitari,
5 Vall d’Hebron Hospital Universitari: Hospital Universitari Vall d'Hebron,
6 Universitat de Barcelona Facultat de Farmacia i Ciencies de l'Alimentacio,
7 Vall d'Hebron Institut de Recerca
https://doi.org/10.21203/rs.3.rs-3736031/v1
This work is licensed under a CC BY 4.0 License
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 status.
Methods
This prospective, cross-sectional, case-control cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers to assess endothelial function and systemic inflammation. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched healthy subjects were included. Regression analysis was used to examine associations between self-reported outcome measures and circulating biomarkers in 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) with the 10-min NASA lean test. Compared with 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 control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did 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 endothelial and inflammatory biomarkers.
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.
Biomarkers
Chronic fatigue syndrome
Endothelial dysfunction
Inflammation
Long COVID
Myalgic encephalomyelitis
Post-acute sequelae of COVID-19
Post-exertional malaise
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