Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes: Cytokine and Growth Factor Reviews

M. Bonafè, F. Prattichizzo, A. Giuliani, G. Storci, J. Sabbatinelli, F. Olivieri

Research output: Contribution to journalArticlepeer-review


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. © 2020 Elsevier Ltd
Original languageEnglish
Pages (from-to)33-37
Number of pages5
JournalCytokine Growth Factor Rev.
Publication statusPublished - 2020


  • Cardiovascular diseases
  • COVID-19
  • Host-directed therapies
  • Inflamm-aging
  • interleukin-6
  • SARS-CoV-2
  • angiotensin converting enzyme 2
  • antivirus agent
  • interferon
  • dipeptidyl carboxypeptidase
  • IL6 protein, human
  • interleukin 6
  • monoclonal antibody
  • tocilizumab
  • adverse outcome
  • Article
  • biological phenomena and functions concerning the entire organism
  • cardiovascular disease
  • chronic disease
  • chronic inflammation
  • comorbidity
  • coronavirus disease 2019
  • cytokine release syndrome
  • disease severity
  • down regulation
  • enzyme activity
  • enzyme defect
  • enzyme regulation
  • geriatric disorder
  • high risk population
  • human
  • immune response
  • immunopathology
  • immunosenescence
  • inflammation
  • male
  • mortality
  • mortality rate
  • nonhuman
  • priority journal
  • Severe acute respiratory syndrome coronavirus 2
  • systemic disease
  • virus cell interaction
  • aged
  • aging
  • Betacoronavirus
  • biosynthesis
  • blood
  • Coronavirus infection
  • female
  • immunology
  • metabolism
  • pandemic
  • pathology
  • severe acute respiratory syndrome
  • very elderly
  • virus pneumonia
  • Aged
  • Aged, 80 and over
  • Aging
  • Antibodies, Monoclonal, Humanized
  • Comorbidity
  • Coronavirus Infections
  • Female
  • Humans
  • Inflammation
  • Interferon Type I
  • Interleukin-6
  • Male
  • Pandemics
  • Peptidyl-Dipeptidase A
  • Pneumonia, Viral
  • Severe Acute Respiratory Syndrome


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