Persistent endotheliopathy may underpin symptoms seen in long COVID

Researchers who have identified sustained endotheliopathy in patients recovering from COVID-19 infection say it raises the ‘intriguing possibility’ that it may underpin the persistent symptoms seen in long COVID.

Their small study of 50 patients reviewed an average 68 days after SARS- CoV-2 infection found significant differences in several pro-thrombotic markers compared with healthy controls.

Writing in the Journal of Thrombosis and Haemostasis, they said they had shown for the first time that sustained endothelial cell activation is common up to 10 weeks after acute COVID infection.

Thrombin generation assays showed significantly shorter lag times, increased endogenous thrombin potential and peak thrombin in those recovering from COVID compared with healthy controls.

And endothelial cell biomarkers including plasma VWF:Ag, VWF propeptide and Factor VIII:C were significantly elevated in the COVID cohort.

These were all also significantly higher in patients who had required hospital admission during their acute COVID illness, in patients over 50 and in those with two or more comorbidities.

The persistent endotheliopathy was independent of ongoing acute phase response or active NETosis, they reported.

Research in a larger group of patients plus comparisons of endothelial cell activation and dysfunction in recovering COVID-19 patients and those who have had other types of severe viral illness are now needed to better understand what is happening, they said.

Study author Dr Helen Fogarty from the Irish Centre for Vascular Biology said while coagulation activation and endothelial dysfunction are hallmarks of acute COVID-19 infection, very little is known about the duration of these pathogenic processes during recovery and whether they may play a role in long COVID syndrome.

‘This research therefore provides novel insights by identifying persistent coagulation potential and endotheliopathy in patients up to 10 weeks following acute infection.

‘Importantly, ongoing coagulation activation directly correlated with reduced exercise tolerance and fatigue, key components of long COVID syndrome,’ she said.

‘Larger studies are required to validate our findings and to explore whether this sustained coagulation activation has a role in stratifying patients at increased risk of thrombotic events after resolution of acute COVID-19 who may benefit from extended duration thromboprophylaxis and in the pathogenesis of long COVID syndrome,’ she added.

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