Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes

Cytokine Growth Factor Rev. 2020 Jun:53:33-37. doi: 10.1016/j.cytogfr.2020.04.005. Epub 2020 May 3.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that four well-recognized features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (i.e. the SARS-CoV-2 receptor); and iv. accelerated biological aging. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

Keywords: COVID-19; Cardiovascular diseases; Host-directed therapies; Inflamm-aging; SARS-CoV-2; interleukin-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Angiotensin-Converting Enzyme 2
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Betacoronavirus / immunology
  • COVID-19
  • Comorbidity
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / pathology*
  • Female
  • Humans
  • Inflammation / pathology
  • Interferon Type I / blood
  • Interferon Type I / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology*
  • Male
  • Pandemics
  • Peptidyl-Dipeptidase A / biosynthesis
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / pathology*
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / mortality
  • Severe Acute Respiratory Syndrome / pathology


  • Antibodies, Monoclonal, Humanized
  • IL6 protein, human
  • Interferon Type I
  • Interleukin-6
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • tocilizumab