Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19
2 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 SISTM - Statistics In System biology and Translational Medicine
5 BPH - Bordeaux population health
6 VRI - Vaccine Research Institute [Créteil, France]
7 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
8 Services de Maladies Infectieuses et Tropicales [CHU Bichat]
9 French COVID cohort study group
10 LilNCog - Lille Neurosciences & Cognition - U 1172
11 CIC 1418 - CIC - HEGP
12 Groupe Henri Mondor-Albert Chenevier
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Résumé
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; and (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 6 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.
Domaines
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