Gene expression profiles of 65 blood samples recovered from 46 COVID-19 convalescent patients and 10 healthy donors were analyzed by RNA-Sequencing.

Purpose: Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19. Methods: We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge. Results: We observed persistent abnormalities until month 6 marked by i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines, ii) a high frequency of central memory CD4+ and effector CD8+ T cells; iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies, iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation. Conclusion: The lack of restoration of gene expression to a normal profile after up to six months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures. Gene expression profiles of 65 blood samples recovered from 46 COVID-19 convalescent patients and 10 healthy donors were analyzed by RNA-Sequencing