Age-Related Differences in Immunological Responses to SARS-CoV-2

Abstract

There is a striking age-related disparity in the prevalence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 infections, which might be explained by age-dependent immunological mechanisms. These include age-related physiological differences in immunological responses, cross-neutralizing antibodies, and differences in levels and binding affinity of angiotensin-converting enzyme 2, the SARS-CoV-2 target receptor; antibody-dependent enhancement in adults manifesting with an overexuberant systemic inflammation in response to infection; and the increased likelihood of comorbidities in adults and the elderly. Emerging immunological phenomena such as Pediatric Multi-System Inflammatory Disorder Temporally associated with SARS-CoV-2 or Multisystem Inflammatory Syndrome in Children are now being observed, though the underlying mechanisms are still unclear. Understanding the mechanisms through which pediatric patients are protected from severe novel coronaviruses infections will provide critical clues to the pathophysiology of coronavirus disease 2019 infection and inform future therapeutic and prophylactic interventions. Asymptomatic carriage in children may have major public health implications, which will have an impact on social and health care policies on screening and isolation practices, school reopening, and safe distancing requirements in the community.

The immune response to SARS-CoV-2 and COVID-19 immunopathology – Current perspectives

“…The interplay between immunosenescence and inflammaging has been hypothesized to contribute to the cytokine storm in elderly patients with COVID-19. 79 Excessive activation of the immune system has also been observed in several autoimmune, infectious, and neoplastic disorders. The term “cytokine storm syndrome” could therefore apply to a group of diseases other than COVID-19 and probably also some clinical stages of COVID-19.…”

Single Cell Transcriptomic Re-analysis of Immune Cells in Bronchoalveolar Lavage Fluids Reveals the Correlation of B Cell Characteristics and Disease Severity of Patients with SARS-CoV-2 Infection

“…Although aging is known to be associated with reduced production of Abs against viral infections, the proportion of Ab-secreting cells among PBMCs collected from elderly COVID-19 patients (i.e., those >70 years of age) is reportedly higher than that of younger COVID-19 patients (i.e., those between 30 and 50 years of age) ( 32 ). In addition, older adults might have larger afucosylation of IgG which strengthen the affinity for Fc receptor ( 33 ), and the responses with afucolsylated IgG are increased in severe COVID-19 patients ( 34 ). Therefore, there is a possibility that aging influences B cell responses and the ADE phenomenon.…”

Environmental Determinants of Coronavirus Disease 2019 (COVID-19)

“…Indeed, the fatality rate among people over 70 years of age diagnosed with COVID-19 was well above 10% but was 0.1% for children and young adults [6]. While rare, cases of severe or fatal COVID-19 do occur in adolescents and young individuals in their twenties [7,8], suggesting either an undiagnosed underlying health condition and/or potential genetic and gene-environment interactions. A growing list of potential gene polymorphisms conferring increased susceptibility to severe COVID-19 is being reported [9].…”

“…Elevated ACE2 expression on epithelial cells, combined with the high affinity of the SARS-CoV-2 spike protein for ACE2 promotes viral infection in vitro [99,100]. The fact that ACE2 expression levels in the airway increase with age is only one potential reason young children have milder COVID-19 symptoms [8]. The hypothesis that severe COVID-19 cases might result from higher tissue levels of ACE2, increased infection and ultimately greater viral load is being actively investigated.…”