AUTHOR=Fionda Cinzia , Ruggeri Silvia , Sciumè Giuseppe , Laffranchi Mattia , Quinti Isabella , Milito Cinzia , Palange Paolo , Menichini Ilaria , Sozzani Silvano , Frati Luigi , Gismondi Angela , Santoni Angela , Stabile Helena 

TITLE=Age-dependent NK cell dysfunctions in severe COVID-19 patients

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1039120

DOI=10.3389/fimmu.2022.1039120

ISSN=1664-3224

ABSTRACT=<p>Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56<sup>low</sup>CD16<sup>high</sup> and CD56<sup>neg</sup> phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β−dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution.</p>