Fig. 1.

Overview of the framework where inflamm-aging is the main phenomenon contributing to the high COVID-19 mortality rate seen in male, elderly, and frail patients. In these individuals, acute SARS-CoV-2 infection compounds their chronic, subclinical, aging-related proinflammatory state (inflamm-aging) which, together with immune senescence and the age- and gender-specific distribution of ACE2 in the airway epithelia, could blunt the antiviral response to inflammation. This model could explain the delayed viral clearance and the high rate of adverse outcomes observed in older patients in the late disease stages. The assessment of selected biological and immunological aging markers could be a valuable strategy for COVID-19 patient risk stratification in the earliest disease stage irrespective of their chronological age. Figure based on the classification of COVID-19 disease states proposed by Siddiqi and Mehra and adapted from the accompanying paper [78]. ACE2, angiotensin converting enzyme 2; cfDNA, cell-free DNA; IFN, interferon.