The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets

Drugs Aging. 2020 Nov;37(11):779-785. doi: 10.1007/s40266-020-00808-4. Epub 2020 Oct 21.

Abstract

This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / pharmacology*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Betacoronavirus* / drug effects
  • Betacoronavirus* / physiology
  • COVID-19
  • Coronavirus Infections* / drug therapy
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / metabolism
  • Coronavirus Infections* / virology
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / immunology
  • Humans
  • Hypertension / drug therapy*
  • Immunologic Factors / pharmacology
  • Inflammation* / drug therapy
  • Inflammation* / immunology
  • Neprilysin / antagonists & inhibitors
  • Pandemics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral* / drug therapy
  • Pneumonia, Viral* / immunology
  • Pneumonia, Viral* / metabolism
  • Pneumonia, Viral* / virology
  • Renin-Angiotensin System / drug effects
  • SARS-CoV-2

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Immunologic Factors
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Neprilysin