The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients’ survival and long COVID
Maddalena Noviello, Rebecca De Lorenzo, Raniero Chimienti, Norma Maugeri, Claudia de Lalla, Gabriel Siracusano, Nicola Ivan Lorè, Paola M. V. Rancoita, Federica Cugnata, Elena Tassi, Stefania Dispinseri, Danilo Abbati, Valeria Beretta, Eliana Ruggiero, Francesco Manfredi, Aurora Merolla, Elisa Cantarelli, Cristina Tresoldi, Claudia Pastori, Roberta Caccia, Francesca Sironi, Ilaria Marzinotto, Fabio Saliu, Silvia Ghezzi, Vito Lampasona, Elisa Vicenzi, Paola Cinque, Angelo A. Manfredi, Gabriella Scarlatti, Paolo Dellabona, Lucia Lopalco, Clelia Di Serio, Mauro Malnati, Fabio Ciceri, Patrizia Rovere‐Querini, Chiara Bonini
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: 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.