PB1380 - Circulating Endothelial Cells as Key Predictors of Fatigue in Long COVID Patients

Background: Long COVID is an heterogenous disease enduring different clinical symptoms, notably fatigue and dyspnea.

Aims: Investigating the enduring presence of clinical symptoms, specifically dyspnea and fatigue, in relation with biomarkers levels in individuals’ post-recovery from COVID-19.

Methods: Consecutive patients with long COVID-19 suspicion were enrolled after 3 to 24 months following an episode of acute SARS-CoV-2 infection.

Results: The study included 137 long COVID patients. 89 (64.9%) patients reported experiencing persistent fatigue while dyspnea was observed in 91 (66.4%) of the study participants. Increased CECs levels was identified as a predictive factor for persistent fatigue (CECs>10: OR 2.62, 95% CI 1.46-4.78, p< 0.001) but not persistent dyspnea. Approximately 51.4% of samples exhibited an increase in CECs during the follow-up period. While no significant differences in CECs levels were found in patients displaying dyspnea, impaired DLCO, or abnormal PFT, a noteworthy increase in CEC levels was observed in patients with persistent fatigue (median :14.0 CECs/mL IQR [5.50-24.50]) compared to those without fatigue (median: 6.0 CECs/mL IQR [3.0-15.0], p=0.008). this result has been found in different initial severity group of patients. In a univariate logistic regression model, persistent fatigue and increased CRP levels were significant predictive factor of displaying increased CECs (above 10 cells/mL). In a multivariate analysis, only acute COVID-19 severity and persistent fatigue remained associated with CECs above 10 cells/mL.

Conclusion(s): CECs emerge as a significant predictive factor for fatigue in individuals with long COVID. Our earlier findings indicated that impaired DLCO is linked to dysfunctional angiogenesis, marked by elevated VEGF-A levels. The current study establishes a connection between CECs and fatigue, irrespective of pulmonary function and VEGF-A. This suggests the existence of multiple forms of long COVID, each associated with distinct vascular biology dysfunctions. Further research is imperative to enhance our understanding of the diagnosis and treatment of patients with these varying manifestations.