E3 PreliminaryPreliminaryPEM ?MechanisticPeer-reviewedMachine draft
Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro.
Flaskamp, Lavinia, Roubal, Constanze, Uddin, Steven et al. · Cells · 2022 · DOI
Quick Summary
This study examined blood samples from people with long COVID and those who developed ME/CFS after COVID-19, comparing them to healthy controls. Researchers tested whether certain proteins in these blood samples could harm the cells that line blood vessels. They found that the blood of ME/CFS patients contained more of these harmful proteins, and the blood samples from both patient groups affected blood vessel cells in different ways that could contribute to the fatigue and other symptoms these patients experience.
Why It Matters
This research provides mechanistic insight into how blood factors from ME/CFS patients might directly damage blood vessel function, a potential explanation for symptoms like fatigue and exercise intolerance. Identifying distinct differences between PCS and PCS/CFS patients at the molecular level could eventually help develop targeted treatments and improve patient stratification.
Observed Findings
- Anti-endothelial cell autoantibodies (AECAs) were significantly more abundant in PCS/CFS patient serum compared to PCS and healthy controls.
- Both PCS and PCS/CFS sera reduced surface expression of several endothelial cell activation markers unexpectedly.
- PCS sera significantly promoted angiogenesis (new blood vessel formation) in vitro, while PCS/CFS sera did not show this enhancement.
- Both patient groups' sera induced release of molecules that inhibit nitric oxide-mediated endothelial relaxation, a key mechanism in blood vessel function.
- Cytokine profiles in serum showed only marginal differences between PCS, PCS/CFS, and healthy control groups.
Inferred Conclusions
- PCS sera may trigger compensatory pro-angiogenic mechanisms to counteract endothelial dysfunction, whereas PCS/CFS patients lack this adaptive response.
- AECA-mediated endothelial damage may represent a distinguishing pathophysiological mechanism in PCS/CFS compared to broader PCS.
- Both patient groups exhibit impaired nitric oxide-dependent endothelial relaxation, contributing to vascular dysfunction and potentially symptom generation.
- The differential functional effects between PCS and PCS/CFS suggest distinct immunopathological mechanisms despite both conditions following COVID-19.
Remaining Questions
What This Study Does Not Prove
This study does not establish that AECAs or the observed blood changes are the primary cause of ME/CFS—only that they are associated with it. The findings are from laboratory experiments with isolated cells and cannot directly prove these mechanisms occur or cause symptoms in living patients. Additionally, correlation between these blood factors and symptom severity was not established.
Tags
Symptom:Fatigue
Biomarker:CytokinesAutoantibodiesBlood Biomarker
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:PEM Not DefinedSmall SampleExploratory OnlyMixed Cohort
Metadata
- DOI
- 10.3390/cells11152376
- PMID
- 35954219
- Review status
- Machine draft
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 8 April 2026