A distinct association of inflammatory molecules with outcomes of COVID-19 in younger versus older adults

Shin, Junghee J.; Jeon, Sangchoon; Unlu, Serhan; Par-Young, Jennefer; Shin, Min Sun; Kuster, John K.; Afinogenova, Yuliya; Kang, Yumi; Simonov, Michael; Buller, Gregory; Bucala, Richard; Kang, Insoo

Aging can alter immunity affecting host defense. COVID-19 has the most devastating clinical outcomes in older adults, raising the implication of immune aging in determining its severity and mortality. We investigated biological predictors for clinical outcomes in a dataset of 13,642 ambulatory and hospitalized adult COVID-19 patients, including younger (age < 65, n = 566) and older (age ≥ 65, n = 717) subjects, with in-depth analyses of inflammatory molecules, cytokines and comorbidities. Disease severity and mortality in younger and older adults were associated with discrete immune mechanisms, including predominant T cell activation in younger adults, as measured by increased soluble IL-2 receptor alpha, and increased IL-10 in older adults although both groups also had shared inflammatory processes, including acute phase reactants, contributing to clinical outcomes. These observations suggest that progression to severe disease and death in COVID-19 may proceed by different immunologic mechanisms in younger versus older subjects and introduce the possibility of age-based immune directed therapies.