A longstanding question has nagged the COVID battle for more than four years: Why does the infection cause severe disease in older people? The question has remained despite a global cadre of medical investigators having produced some of the reasons—but not the entire story.

Ever since the beginning of the pandemic in 2020, it has been abundantly clear that older adults are at substantial risk of severe, even fatal COVID. Yet, the underlying mechanisms for their susceptibility were not always clear despite studies that took co-morbidities into account, like diabetes, heart and lung disorders, and other chronic vagaries of age that can worsen a bout with an infectious disease.

To date, scientists have blamed a dysregulated immune system, an age-related affinity toward excessive blood clotting, and an overall decline in the key soldiers of the adaptive immune system, T and B cells, to explain increased risks for severe COVID in the aging population. And while all of those factors may play a role, an inevitable question looms large: Why?