The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging"

Inflamm Res. 2020 Sep;69(9):825-839. doi: 10.1007/s00011-020-01372-8. Epub 2020 Jun 11.


Purpose: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection.

Methods: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed.

Results: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.

Keywords: ACE2 receptor; Autophagy; COVID-19; Cytokine storm; Senescent cell; Vitamin D.

Publication types

  • Review

MeSH terms

  • Adipocytes / cytology
  • Age Factors
  • Aged
  • Aging*
  • Angiotensin II Type 2 Receptor Blockers / pharmacology
  • Autophagy
  • Betacoronavirus
  • COVID-19
  • Cellular Senescence
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / physiopathology*
  • Cytokine Release Syndrome / virology*
  • Cytokines / immunology
  • Humans
  • Immune System
  • Inflammation / immunology*
  • Inflammation / physiopathology
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / physiopathology*
  • Reactive Oxygen Species / metabolism
  • Receptor, Angiotensin, Type 2 / metabolism
  • SARS-CoV-2
  • Vitamin D / metabolism
  • Vitamin D Deficiency


  • Angiotensin II Type 2 Receptor Blockers
  • Cytokines
  • Reactive Oxygen Species
  • Receptor, Angiotensin, Type 2
  • Vitamin D