By Denise Baez
Increased levels of circulating endothelial cells appear to be associated with severe forms of coronavirus disease 2019 (COVID-19), according to a study published in The Journal of Infectious Diseases.
In a study of 99 patients with COVID-19, those who required admission to the intensive care unit (ICU) had significantly higher circulating endothelial cells than patients who did not require treatment in the ICU. In addition, the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines.
“Any endothelial injury, including infections, impairs regulatory functions of the endothelium with subsequent vasoconstriction, ischemia, inflammation and activation of the coagulation cascade, ultimately leading to vessels denudation and exposure of the thrombogenic subendothelium,” explained Christophe Guervilly, MD, North Hospital, APHM, Chemin des Bourrely, Marseille, France, and colleagues. “Circulating endothelial cells are stressed cells detached from injured vessels…[and] are detectable at very low levels in healthy conditions. Increased circulating endothelial cell counts have been reported in various diseases of inflammatory, infectious or ischemic origin, where they evidence a profound vascular insult and are indicative of disease severity.”
All patients in the study presented with viral pneumonia and tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swab, sputum or bronchoalveolar lavage. Of the hospitalised patients, 19 required admission to the intensive care unit (ICU) due to the severity of oxygen requirements. Blood samples were collected within 48 hours of patient admission.
Patients requiring ICU care were younger than patients hospitalised in non-ICU departments (median age, 55.3 vs 68.2 years), and had a higher percentage of patients that were obese (47% vs 19%). None of the patients in ICU had chronic kidney disease (CKD) compared with 28 (35%) patients in the non-ICU group. The non-ICU group also had more patients with hypertension (54% vs 21%) and cardiovascular disease (30% vs 0%). All patients in the ICU group required invasive mechanical ventilation.
Overall, 55% of hospitalised patients had circulating endothelial cell counts >20 cells/mL; however, levels were significantly higher in ICU patients than in non-ICU patients (49 [24-103] vs 18 [6-70] cells/mL; P = .03). Circulating endothelial cell counts were negatively correlated with platelet (r = -0.334; P = .0008) and lymphocyte counts (r = -0.336; P = .0007). There was also a positive correlation between the circulating endothelial cell counts and the length of hospital stay (r =0 .261; P = .02).
The plasma concentrations of IL-6, IP-10, E-Selectin, and sVCAM-1 were also significantly higher in ICU patients than non-ICU patients, but only sVCAM-1 (r = 0.374; P = .0002) and IP-10 concentrations (r = 0.487; P < .0001) correlated with circulating endothelial cell counts.
Multivariate analysis integrating age, obesity, hypertension, CKD, cardiovascular disease, and ICU hospitalisation showed that only CKD could be identified as independently associated with CEC counts (P = .011). Admission in ICU was also associated with high CEC levels independently of all comorbidities that differ between ICU and non ICU patients ( P = .046). Consequently, after the exclusion of patients with CKD, the difference between CEC levels in ICU patients compared to nonICU patients was even more pronounced (P = .002).
“This is the first observation of increased circulating endothelial cell counts in the blood of patients with COVID-19,” the authors wrote. “Circulating endothelial cell counts were significantly higher in patients admitted to the ICU, positively correlated with the length of hospital stay, and were inversely correlated with platelet and lymphocyte counts. Increased CEC levels were also associated with increased concentrations of the cytokine IP10 and sVCAM-1. These results provide in vivo evidence that a marked and widespread endothelial injury occurred in the course of proinflammatory vessel activation in the more severe forms of COVID-19.”