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J Med Virol . High-Dimensional Immunophenotyping of Post-COVID-19 and Post-Influenza Patients Reveals Persistent and Specific Immune Signatures Aft

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Jun;97(6):e70435.
doi: 10.1002/jmv.70435. High-Dimensional Immunophenotyping of Post-COVID-19 and Post-Influenza Patients Reveals Persistent and Specific Immune Signatures After Acute Respiratory Infection

Francisco Pérez-Cózar[SUP] 1 [/SUP], Paloma Cal-Sabater[SUP] 2 [/SUP], Paulina Rybakowska[SUP] 1 [/SUP], Elisa Arribas-Rodríguez[SUP] 2 [/SUP], Aida Fiz-López[SUP] 2 [/SUP], Antonio García-Blesa[SUP] 2 [/SUP], Juan Hernández[SUP] 2 [/SUP], Sara Gutiérrez[SUP] 3 [/SUP], Pablo Tellería[SUP] 3 [/SUP], Cristina Novoa[SUP] 3 [/SUP], Silvia Rojo Rello[SUP] 4 [/SUP], Ángel De Prado[SUP] 2 [/SUP], Cándido Pérez[SUP] 2 [/SUP], Rosa Sedano[SUP] 3 [/SUP], Marta Domínguez-Gil[SUP] 5 [/SUP], María Jesús Peñarrubia[SUP] 6 [/SUP], Daan K J Pieren[SUP] 7 [/SUP], José A Garrote[SUP] 2 [/SUP], Eduardo Arranz[SUP] 2 [/SUP], José María Eiros[SUP] 4 [/SUP], Eduardo Tamayo[SUP] 8 [/SUP], Antonio Orduña[SUP] 5 [/SUP], Cécile A C M van Els[SUP] 7 [/SUP], Carlos Dueñas[SUP] 3 [/SUP], Concepción Marañón[SUP] 1 [/SUP], David Bernardo[SUP] 9 [/SUP], Sara Cuesta-Sancho[SUP] 9 [/SUP]



Affiliations
Abstract

Long-term consequences of SARS-CoV-2 infection are unknown since recovered individuals can experience symptoms and latent viral reactivation for months. Indeed, acute post-infection sequelae have also been observed in other respiratory viral infections, including influenza. To characterize post-COVID-19 and post-influenza induced alterations to the cellular immunome, peripheral blood mononuclear cells (PBMCs) were obtained from patients 3 months after recovery from COVID-19 (n = 93) or influenza (n = 25), and from pre-pandemic healthy controls (n = 25). PBMCs were characterized using a 40-plex mass cytometry panel. Principal component analysis (PCA), classification models, and K-means clustering were subsequently applied. PCA identified distinct immune profiles between cohorts, with both post-COVID and post-flu patients displaying an altered chemokine receptor expression compared to pre-pandemic healthy controls. These alterations were more prominent in post-COVID patients since they exhibited highly increased expression of chemokine receptors CXCR3 and CCR6 by various lymphoid populations, while post-influenza patients mainly showed a decrease in CCR4 expression by naïve T cells, monocytes, and conventional dendritic cells. Classification models using immunophenotyping data confirm the three groups, while K-means clustering revealed two subgroups among post-COVID patients, with younger patients showing more pronounced immune alterations in the chemokine receptor profile, independently of long COVID symptoms. In conclusion, post-COVID and post-influenza patients exhibit distinct and unique persistent immune alterations. Understanding these altered immune profiles can guide targeted therapies for post-COVID syndrome and highlight differences in immune recovery from various respiratory infections.

Keywords: immune signature; immunome; post‐COVID‐19; post‐influenza.

 
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