Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19

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Hocini, Hakim | Wiedemann, Aurélie | Blengio, Fabiola | Lefebvre, Cécile | Cervantes-Gonzalez, Minerva | Foucat, Emile | Tisserand, Pascaline | Surenaud, Mathieu | Coléon, Séverin | Prague, Mélanie | Guillaumat, Lydia | Krief, Corinne | Fenwick, Craig | Laouénan, Cédric | Bouadma, Lila | Ghosn, Jade | Pantaleo, Giuseppe | Thiébaut, Rodolphe | Abel, Laurent | Abrous, Amal | Andrejak, Claire | Angoulvant, François | Bachelet, Delphine | Bartoli, Marie | Behilill, Sylvie | Beluze, Marine | Bhavsar, Krishna | Chair, Anissa | Charpentier, Charlotte | Chenard, Léo | Chirouze, Catherine | Couffin-Cadiergues, Sandrine | Couffignal, Camille | Castro, Nathalie, De | Debray, Marie-Pierre | Deplanque, Dominique | Descamps, Diane | Diallo, Alpha | Silva, Fernanda, Dias Da | Dorival, Céline | Duval, Xavier | Eloy, Philippine | Enouf, Vincent | Esperou, Hélène | Esposito-Farese, Marina | Etienne, Manuel | Florence, Aline-Marie | Gaymard, Alexandre | Gigante, Tristan | Gilg, Morgane | Goehringer, François | Guedj, Jérémie | Houas, Ikram | Hoffmann, Isabelle | Hulot, Jean-Sébastien | Jaafoura, Salma | Jamard, Simon | Kafif, Ouifiya | Khalil, Antoine | Lafhej, Nadhem | Laribi, Samira | Le, Minh | Hingrat, Quentin, Le | Mestre, Soizic, Le | Letrou, Sophie | Lina, Bruno | Lingas, Guillaume | Malvy, Denis | Mentré, France | Mouquet, Hugo | Neant, Nadège | Paul, Christelle | Papadopoulos, Aurélie | Petrov-Sanchez, Ventzislava | Peytavin, Gilles | Piquard, Valentine | Picone, Olivier | Rosa-Calatrava, Manuel | Rossignol, Bénédicte | Rossignol, Patrick | Roy, Carine | Schneider, Marion | Tardivon, Coralie | Timsit, Jean-François | Tubiana, Sarah | Werf, Sylvie, Van. Der | Visseaux, Benoit | Lévy, Yves

Edité par CCSD ; Springer Verlag -

International audience. 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.

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