Aging, Male Sex, Obesity, and Metabolic Inflammation Create the Perfect Storm for COVID-19.

Coronavirus disease 2019 (COVID-19) is a novel threat that seems to result from the collusion between a new pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and an existing pandemic of metabolic disease driven by obesity. This Perspective explores the evolving epidemiological, clinical, biological, and molecular evidence to propose an unfolding paradigm in which old age, chronic metabolic disease (such as obesity, type 2 diabetes, and metabolic syndrome), and male biological sex produce a deadly symbiosis of dysregulated immunometabolism and chronic systemic inflammation that intensifies virally induced hyperinflammation associated with SARS-CoV-2 infection. It is intended to inspire new research directions and stimulate funding in this field.