Post-COVID symptoms and endotypes are associated with the inability to modulate the trajectory of immune and hemostatic pathways

Persistent symptoms after COVID-19 infection can affect almost half of COVID-19 survivors, leading to poor quality of life. Despite its prevalence, the pathophysiology of this phenomenon is poorly understood. We analyzed differences in gene expression between patients with and without post-COVID symptoms in hospital, at follow-up, and longitudinally. As part of the Banque Québécoise de la COVID-19 biobank, 24 adult patients who were hospitalized due to respiratory COVID-19 were enrolled. Whole blood was collected within the first 10 days in hospital and 4-12 weeks after discharge. K-medoids clustering was performed to further separate patients into clusters/endotypes for DE analysis and pathway enrichment. We found that high rates of post-COVID symptoms in hospitalized patients were associated with an inability to mount, and subsequently resolve by 4-12 weeks after discharge, a robust early response involving immune and hemostatic pathways, which was seen in two of three endotypes. Overall design: To identify gene expression changes associated with post-COVID symptoms longitudinally and identify mechanistic endotypes related to symptoms. Samples were sequenced over three sequencing runs. K-medoid clustering resulted in three endotypes: cluster 1 (resolving), cluster 2 (dampened), and cluster 3 (activated).