COVID-19 in the Context of Aging

It is widely appreciated that old people have a poor time of it when it comes to infectious disease. Seasonal influenza kills tens of thousands of older people every year in the US alone. The aged immune system functions poorly, and vaccinations for many conditions have low success rates in older people. Thus the vast majority of COVID-19 deaths are old people exhibiting immunosenescence. Given that the world at large seems to be entirely accepting of the yearly toll of influenza, while COVID-19 is classed as an apocalypse of some sort, one has to wonder how much of the hysteria surrounding COVID-19 stems from the rare - but highly publicized - deaths of younger individuals. Or perhaps if the rising toll of every influenza season was reported in the same way as deaths from COVID-19, more might be done? Human psychology is a strange thing.

An enormous amount of government and other funding will be directed towards fundamental infectious disease research in the years ahead, once things have settled down somewhat and COVID-19 has faded into the backdrop. That is one consequence of a pandemic that captures the attention of the world to the degree that this one has, deservedly or otherwise. This was perhaps the perfect storm, as ominous rumblings and awareness initiatives have been ongoing for some time regarding the threat of SARS-like viruses making the leap from animals to humans. A critical mass was finally reached. That COVID-19 has so far turned out to be less terrible than suspected at the outset is beside the point. The organizations of the world were primed to react in the way they are now to the first SARS-like virus that appeared remotely threatening.

The prospect of a large increase in funding for infectious disease and immunology research means that scientists in every relevant field of study are racing to position themselves to try to capture a portion of those funds. We outsiders don't see the ferocious pace of grant writing, but published papers are a visible sign of this energetic process. A few recent examples are noted below. Researchers involved in immunology and aging are taking this moment in history to remind the world that, yes, the immune system decays with age, old people bear the brunt of infectious disease as a result, and perhaps we should do something about this, now that we can target the mechanisms of aging - the cause of immunosenescence.

Covid-19 and Immunity in Aging Populations - A New Research Agenda

As we age, health conditions associated with aging, particularly noncommunicable diseases such as heart disease, cancers, and metabolic and autoimmune diseases, combined with treatments for these diseases and with immune senescence, substantially affect responses to vaccines and infectious diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as the receptor for SARS-CoV-2, the virus that causes Covid-19, and it has been suggested that differential levels of ACE2 in the cardiac and pulmonary tissues of younger versus older adults may be at least partially responsible for the spectrum of disease virulence observed among patients with Covid-19.

Even as the brunt of severe illness from Covid-19 is being borne by aging adults, we are navigating partially blind in efforts to develop vaccines and therapies to stop this and future pandemics, since we lack knowledge of the mechanisms of immunity to protect this population. If we can delineate principles of effective immunity in the elderly, we might also be able to develop new strategies for broader disease prevention and control in older populations.

COVID-19 is an emergent disease of aging

Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

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 some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: (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 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and (iv) accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state.

Comments

This COVID fuss was the drop that filled the glass for me and now I'm 100% sure: the bussiness of all media is not to inform the public, but to alarm the public. There are no exceptions for any media nor any field, be it medicine, politics, crime, nutrition, the internet, or what our children do, be it right-wing media or left-wing media, TV or paper.

I don't think this will benefit antiaging research. All the extra funds will go to infectious diseases research.

Posted by: Antonio at April 28th, 2020 6:11 PM

An easy way to advance the use of anti-aging science against Covid-19 is to petition WHO to release data concerning the biological characteristics of susceptible older people. Aubrey de Grey is one of the authors of the petition and it only takes a few minutes to sign and lend support:

https://www.change.org/p/dr-tedros-adhanom-ghebreyesus-we-call-for-open-anonymized-medical-data-on-covid-19-and-aging-related-risk-factors-dadcacdc-2e0d-47e1-a4fc-f2bdfdf3f1f7

A universal antiviral therapy DRACO has languished from a lack of support and also has a petition at change.org. DRACO was presented at the SENS6 conference. This would help protect against future emerging viruses:

https://www.change.org/p/world-health-organization-bring-back-draco-antiviral-against-coronavirus-disease-covid-19

Posted by: Morpheus at April 29th, 2020 1:00 AM

@Morpheus: I never sign change.org petitions. Anybody can create multiple accounts there and sign several times.

@Florin: I wonder what happened to DRACO too and why it never got funding from Kizoo, Juvenescence or any other investor in our community.

Posted by: Antonio at April 29th, 2020 6:18 AM

"That COVID-19 has so far turned out to be less terrible than suspected at the outset is beside the point."
That's because of the lockdown. Just look at the curve to see where it would have gone had the virus been treated like the flu. You can't argue with excess mortality. And frankly I can't understand why anti-aging advocates don't seem to care about a disease that affects disproportionally the old.
Having said that I think that - in spite of the inevitable recession - the world's "hysteric" response to Covid is a blessing in disguise as it shows that people do care about the elderly.
And it will result in greater focus on biotech, with research on the immune system eventually branching off into even more useful fields.
Perhaps more importantly this experience will shake up the regulatory process, which is the greatest obstacle to translational efforts and thus therapies arriving before everyone on this forum has turned into fertiliser.
In other words, the crisis has a huge silver lining.
https://www.statnews.com/2020/04/27/biotech-century-begins-with-covid-19-pandemic/

Posted by: Barbara T. at April 29th, 2020 9:13 AM

Actually, the high mortality starts *after* the lockdown and it seems to be very country-specific (and even region-specific, in the case of the UK): https://www.euromomo.eu/graphs-and-maps/

Posted by: Antonio at April 29th, 2020 4:40 PM

While millions of people could die if there were no lockdowns, what might not be so obvious is that if SENS research is significantly slowed down by the lockdowns, millions of people will die by missing out on LEV. To avoid at least some of the effects of the lockdowns, medical research should be declared an essential service everywhere.

Posted by: Florin at April 29th, 2020 5:53 PM

"Actually, the high mortality starts *after*".
Obviously, given the following:
1. 2-4 weeks between first reported death and start of the lockdown in the face of 2-10 weeks between first symptoms and death.
2. The transmission rate is exponential.
***
"It seems to be very country-specific"
Obviously again since:
1. Belgium reports even *suspected* Covid deaths while other countries don't test and without a positive result they won't put Covid on the death certificate - even if the patient died of bilateral interstitial pneumonia as per radiographic evidence.
***
"even region-specific, in the case of the UK"
And again given that:
1. Different regions within the same country had different points of entry for the virus (e.g. very many in Lombardy, very few in Sicily), which led to different prevalence throughout the territory.
2. Different demographics led to different transmission rates (e.g. sitting on the tube in London during rush hour is not the same as biking in Cambridge or driving through the Scottish highlands), which resulted in different prevalence throughout the territory.
Which means that:
3. Since prevalence isn't the same everywhere, in areas where cases overwhelm hospital capacity mortality is higher.
4. And since you mention the UK, until today only Scotland and Wales reported nursing home deaths while England didn't. The addition of 4240 cases changes the meaning of whatever data you were looking at.

WHY IS THIS STILL A TOPIC?
***
"medical research should be declared an essential service everywhere."
Hopefully. Check the link I pasted: I don't seem to be the only one to think that this could lead to a positive paradigm shift.

Posted by: Barbara T. at April 29th, 2020 7:05 PM

I don't see what less regs have to do with the lockdowns. While there might be silver linings to this pandemic, it's likely to be net negative for SENS and medical research in general, excluding communicable disease research.

Besides physically slowing research, another problem with the lockdowns is their potential to significantly reduce funding for SENS research and investor interest in SENS-focused startups by destroying economic activity and thus wealth. Perhaps most economies with bounce back quickly like nothing happened due to massive government financial support but that outcome is uncertain and kind of unlikely. And the longer that the lockdowns drag on, the longer SENS research will suffer. Would millions more dead as a result of no lockdowns generate the same level of economic damage? Maybe, but I'm skeptical.

Near-lockdown in the Bay Area 'ratchets up' challenges for local biotechs and labs
https://www.statnews.com/2020/03/17/coronavirus-near-lockdown-bay-area-challenges-biotech-labs/

Posted by: Florin at April 29th, 2020 8:37 PM

Neither I nor the article I linked to say anything about the lockdowns helping the regulatory system.
I was simply responding to someone who doubts that they are slowing the virus.
But the pandemic and the panicked response of the world at the prospect of OLD people dying will - that's the silver lining I was talking about.
As for funding, there's always money around for what people (i.e. billionaires, governments) want.
It never used to go towards medical research but maybe after this it will since strenghtening the elderly (so for all intents and purposes rejuvenating them) should be seen as a good investment.
My point is, I'd rather stop stressing about the immediate-term fallout and start thinking about the greater positive impact of the pandemic if a paradigm shift does come to pass.

Posted by: Barbara T. at April 29th, 2020 9:20 PM

Sweden isn't doing too badly, and in fact, its death rate has peaked and is going down. It doesn't have a lockdown on everything; nursing homes are locked down, but the rest is just semi-voluntary social distancing (business are shut down only if they violate the rules) and even masks aren't officially recommended.

https://www.euromomo.eu/graphs-and-maps/

Posted by: Florin at April 29th, 2020 10:16 PM

I highly doubt that attitudes will change for several reasons.

1) The panic seemed to come from the fear that the healthcare system would collapse and the number of people that could die regardless of their age.
2) Old people already die in droves and there's no massive push to rejuvenate them.
3) A future pandemic may kill more younger people than the old like the Spanish Flu did. That undercuts the argument that rejuvenating the immune system could help.

As for funding always being available, the problem will be that it will probably be less available.

Posted by: Florin at April 30th, 2020 12:15 PM

This high resolution model (only a model but quite unique in its granularity) suggests the positive impact of tough measures in one of the most impacted countries (Italy) during the emergency. They look having been necessary and effective in avoiding at least 200'000 hospitalizations. The model would also show ~8x more total infections than reported last march which should be confirmed and possibly guide policies (and lower CFR). To me it is quite obvious either you strategically and immediately implement the gold standard of epidemiology (test, isolate, track) in parallel working on a treatment or the measures which all countries, to a more or less extent compatible with many local factors took, need to be taken in a corresponding less idealistic situation. Also, many electronic tracking system are being deployed in many countries post more/less confinement measures as I write according to local regulations and privacy preserving approaches. I wish for a country protecting the elderly population and a serious anti-aging approach strengthening the host. I hope SENS will emerge reinforced from this crisis.
https://actu.epfl.ch/news/containment-measures-avoid-200000-hospitalizations/
https://www.pnas.org/content/early/2020/04/22/2004978117

Posted by: albedo at May 3rd, 2020 2:58 PM

It looks like the excess mortality data for Sweden might not be complete, but all of it should be available in a few weeks and enough to determine whether the drop in deaths is real.

Requiring everyone to wear masks and face shields might make it possible to reopen almost everything, but it might be too late for contract tracing by itself to work well.

https://jamanetwork.com/journals/jama/fullarticle/2765525

Posted by: Florin at May 4th, 2020 1:51 AM

A highly recommended read: enjoyable and playable with many scenarios possible. Much worth the time for understanding. Also, accordingly, tracking very much in scope as "lockdown isn't a cure, it's just a restart" and we might face more possibly lighter that the one we had.
What Happens Next?
COVID-19 Futures, Explained With Playable Simulations
https://ncase.me/covid-19/

Posted by: albedo at May 4th, 2020 4:28 PM

Covid is a terrible disease, but besides covid there are at least 6 other species of corona viruses, many species of flu and common cold viruses. We live in the dark age of frequent pandemics. The solution to this awful predicament is to decrease the global population -voluntarily. In Antarctica, continent where human population is small, there were no cases of covid 19. With drastically smaller population social and physical distancing will be much easier and pandemics will be prevented. Choose to have fewer children or no children at all.
Pandemics are man-made disasters. As a side-effect benefit with smaller population there will be less pollution and much less humanly-caused climate change.

Posted by: Nicholas d. at May 25th, 2020 9:22 PM

@Nicholas d
You cure is worse than the disease

Posted by: Cuberat at May 26th, 2020 2:18 PM

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