Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity

Abstract

Human coronaviruses (hCoVs) cause severe respiratory illness in the elderly. Age-related impairments in innate immunity and suboptimal virus-specific T cell and antibody responses are believed to cause severe disease upon respiratory virus infections. This phenomenon has recently received increased attention, as elderly patients are at substantially elevated risk for severe COVID-19 disease and experience increased rates of mortality following SARS-CoV-2 infection compared with younger populations. However, the basis for age-related fatal pneumonia following pathogenic hCoVs is not well understood. In this Review, we provide an overview of our current understanding of hCoV-induced fatal pneumonia in the elderly. We describe host immune response to hCoV infections derived from studies of young and aged animal models and discuss the potential role of age-associated increases in sterile inflammation (inflammaging) and virus-induced dysregulated inflammation in causing age-related severe disease. We also highlight the existing gaps in our knowledge about virus replication and host immune responses to hCoV infection in young and aged individuals.

Figure 1. Immune response to respiratory hCoV infection in young and aged individuals.

In young hosts, hCoV infection induces an early elevation of IFN-I and IL-12 responses and controlled proinflammatory cytokine/chemokine production, leading to effective adaptive immunity and enhanced virus clearance. In contrast, aged hosts mount reduced and delayed IFN-I and IL-12 responses and excessive proinflammatory cytokine/chemokine responses, leading to excessive inflammation, impaired adaptive immune response, delayed virus clearance, and fatal pneumonia.