By: Alex Zhavoronkov

In: Aging

Date: 31 March, 2020

Summary

• COVID-19 disproportionately harms the elderly.
  • Infection rates, severity, and lethality all increase with age.
  • Mostly because of higher levels of comorbidity among elderly.
• May also be due to decreased immune function.
  • Immune system deteriorates with age.
• Decreased immune function may make vaccines and treatments less effective for elderly.
• Strategies to boost immunity may help decrease infection rates.
  • Rapamycin, NAD boosters, and others.
  • Need more research.
• Highlights the need to understand biological aging to better protect elderly population.
  • To help assess the need for geroprotective interventions.

COVID-19 is a gerolavic, disproportionately affecting the elderly.

• Gerophilic versus gerolavic:
  • Gerophilic: pathogens that are more infectious and prevalent in the elderly.
  • Gerolavic: infections that are more widespread but disproportionately affect the elderly.
• COVID-19 = gerolavic.
  • Statistics indicate that infectivity, severity and lethatility of COVID-19 are age-related.
  • Increase in age -> increase is infections, severity and fatalities.
• COVID-19 accelerates and compresses fatalities.
  • May not be the only cause of fatality.
  • Difficult to disentangle from comorbidity, lifestyle, etc.

Immune system deteriorates with age, driving higher infections, severity and outcomes.

• Immunosenescence:
  • Gradual deterioration of immune system with age.
• Driven by thymic involution.
  • The thymus is a specialized lymphoid organ of the immune system.
    • Positioned in front of the heart, behind the sternum.
  • Within the thymus, T cells mature.
    • T cells are critical to the adaptive immune system (adapt to foreign invaders).
  • Most active in fetal and neonatal life.
    • Continues to grow after birth reaching the relative maximum size by puberty.
    • By early teens, thymus begins to decrease in size and activity (involution).
  • Thymus is gradually replaced by adipose tissue (fat).
    • Atrophy of thymus is due to the increased circulating level of sex hormones.
  • T cells exiting the thymus decrease significantly with age.
• Because of this, elderly have reduced ability to resist infection.
  • Infection produces biological damage and loss of homeostasis.
  • Accelerated aging and the development of age-related diseases.
  • Increase in multi-morbidity.

Classic treatments for infectious diseases: vaccines and anti-virals.

• Vaccines.
  • May be the best preventative strategy.
  • Reduce infection rates, severity, and lethality of COVID-19.
  • Success of a vaccine partly depends on similarity of vaccine strain with viral pathogenic strain.
  • For example, influenza, vaccination based on predictions of strain variants.
• Antivirals.
  • Prophylactic treatment prior to symptom onset in high-risk groups or after exposure to virus.
  • Alternative preventative strategy against viral disease.
  • For example, for influenza, the neuraminidase inhibitors oseltamivir and zanamivir.
  • Reduce symptom duration, and reduce complications and transmission risk.
  • Greatest benefit when drugs are administered 24-30 hours prior to symptom onset.

Success of vaccines may be lower in elderly.

• Individual’s immune response must be sufficiently strong.
  • First, mount a reaction to the vaccine.
  • Later, confer protection against the pathogen, should exposure occur.
• Vaccines do not provide complete protection in older populations.
  • Due to age-related declines in immune function and accumulation of multi-morbidities.
  • Outbreaks can occur in elderly nursing homes even with vaccination rates at 80-98%.

Need to improve immune system to reduce infection risk, symptom severity, or improve vaccine efficacy.

• Even with successful vaccine for SARS-CoV-2, will need something to boost immune response.
• Strategies to improve immune system in the elderly.
  • Rapamycin and rapalogs.
    • Immunosuppressant, but may boosts T cell responses in reaction to pathogen infection and vaccination.
    • Also, morbidity from coronavirus infections may occur from secondary overactive immune responses.
  • Metformin.
    • Lowers blood sugar.
  • NAD boosters.
    • May enhance DNA repair.
  • Others.
    • Senolytics, stem cell treatment.
• To be used in isolation or combination with other therapies.
• Lack of clinical evidence to support their immediate use.

Biological age is more important than chronological age.

• A person’s chronological age is not as important as their biological age.
  • Need to develop accurate aging biomarkers.