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

2023; Springer Science+Business Media; Volume: 43; Issue: 5 Linguagem: Inglês

10.1007/s10875-023-01459-x

1573-2592

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

Inflammasome and immune disorders

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.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.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.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.