AUTHOR=Noviello Maddalena , De Lorenzo Rebecca , Chimienti Raniero , Maugeri Norma , De Lalla Claudia , Siracusano Gabriel , Lorè Nicola Ivan , Rancoita Paola Maria Vittoria , Cugnata Federica , Tassi Elena , Dispinseri Stefania , Abbati Danilo , Beretta Valeria , Ruggiero Eliana , Manfredi Francesco , Merolla Aurora , Cantarelli Elisa , Tresoldi Cristina , Pastori Claudia , Caccia Roberta , Sironi Francesca , Marzinotto Ilaria , Saliu Fabio , Ghezzi Silvia , Lampasona Vito , Vicenzi Elisa , Cinque Paola , Manfredi Angelo Andrea , Scarlatti Gabriella , Dellabona Paolo , Lopalco Lucia , Di Serio Clelia , Malnati Mauro , Ciceri Fabio , Rovere-Querini Patrizia , Bonini Chiara TITLE=The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients’ survival and long COVID JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1381091 DOI=10.3389/fimmu.2024.1381091 ISSN=1664-3224 ABSTRACT=Introduction

SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

Methods

We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.

Results

More than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14+CD91+ monocytes, and high CD8+ Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.

Discussion

These results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.