Effect of Age on Innate and Adaptive Immunity in Hospitalized COVID-19 Patients

Cham, Lamin B.; Pahus, Marie Høst; Grønhøj, Kristoffer; Olesen, Rikke; Ngo, Hien; Monrad, Ida; Kjolby, Mads; Tolstrup, Martin; Gunst, Jesper Damsgaard; Søgaard, Ole S.

An effective but balanced cellular and inflammatory immune response may limit the severity of coronavirus disease (COVID-19), whereas uncontrolled inflammation leads to disease progression. Older age is associated with higher risk of COVID-19 and a worse outcome, but the underlying immunological mechanisms for this age-related difference are not clear. We investigated the impact of age on viral replication, inflammation, and innate and adaptive cellular immune responses in 205 hospitalized COVID-19 patients. During the early symptomatic phase of COVID-19, we found that patients above 65 years had significantly higher viral load, higher levels of proinflammatory markers, and inadequate mobilization and activation of monocytes, dendritic cells, natural killer cells, and CD8 T cells compared to those below 65 years. Our study points toward age-related deficiencies in the innate immune cellular response to SARS-CoV-2 as a potential cause of poorly controlled viral replication and inflammation during the early symptom phase and subsequent disease progression.