Age-related differences in the immune response could contribute to determine the spectrum of severity of COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), can present with a wide spectrum of severity. Elderly patients with cardiac, pulmonary and metabolic comorbidities are more likely to develop the severe manifestations of COVID-19, which are observed in less than 5% of the pediatric patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators, strongly contributing to the pulmonary and systemic manifestations in COVID-19. In children, the immune dysregulation following SARS-CoV-2 can also be responsible of a severe disease phenotype defined as multisystem inflammatory syndrome in children. As the immune system undergoes a complex process of maturation from birth to adult age, differences in the immune and inflammatory response could have a significant impact in determining the spectrum of severity of COVID-19. Indeed, children show a higher ability to respond to viral infections and a reduced baseline pro-inflammatory state compared with elderly patients. Age and comorbidities contribute to disease severity through immune-mediated mechanisms, since they are associated with a chronic increase of pro-inflammatory mediators, and cause an enhanced susceptibility to develop an immune dysregulation following SARS-CoV-2 infection. Also the expression of ACE2, the receptor of SARS-CoV-2, varies with age, and is linked to the immune and inflammatory response through a complex, and not completely elucidated, network. This paper reviews the peculiar immunopathogenic aspects of COVID-19, with a focus on the differences between adult and pediatric patients.

Keywords: ACE2; children; coronavirus; cytokine storm; immune dysregulation; multisystem inflammatory syndrome in children (MIS-C).

Figure 1

Pathogenic model of severe COVID‐19. The left side of the figure shows the activation of innate and adaptive immune response following viral infection. The right side analyzes how impaired immunity, immune dysregulation, and uncontrolled inflammation led to massive tissue damage, thus enhancing the inflammatory response, finally leading to ARDS, septic shock and MOF. ARDS, acute respiratory distress syndrome; MOF, multiorgan failure