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Researchers on Monday announced the most comprehensive estimates to date of elderly people’s elevated risk of serious illness and death from the new coronavirus: Covid-19 kills an estimated 13.4% of patients 80 and older, compared to 1.25% of those in their 50s and 0.3% of those in their 40s.

The sharpest divide came at age 70. Although 4% of patients in their 60s died, more than twice that, or 8.6%, of those in their 70s did, Neil Ferguson of Imperial College London and his colleagues estimated in their paper, published in Lancet Infectious Diseases.

The new estimates come as scientists have been scrambling to figure out the underlying reasons for older people’s greater susceptibility to the virus — and, in particular, why some mount a stronger immune response than others.

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It starts with preexisting conditions: Data from China show that such comorbidities dramatically raise the risk of dying from Covid-19. But chronic illnesses may be not only a contributor to Covid-19 deaths but also a mark of biological aging and declining immunity.

“It is not chronological age alone that determines how one does in the face of a life-threatening infection such as Covid-19,” cautioned geriatrician and gerontologist George Kuchel of the University of Connecticut. “Having multiple chronic diseases and frailty is in many ways as or more important than chronological age. An 80-year-old who is otherwise healthy and not frail might be more resilient in fighting off infection than a 60-year-old with many chronic conditions.” Reason: She may have a younger immune system.

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The new calculations, based on 70,117 laboratory-confirmed and clinically-diagnosed cases in mainland China and 689 cases among people evacuated from Wuhan on repatriation flights, allowed the Imperial College researchers to estimate the overall death rate from the disease. In the outbreak’s early weeks that was thought to be as high as 3% to 8%. Instead, the fatality rate among people with confirmed disease is 1.38%, they concluded.

That supports an estimate by researchers at the Harvard T.H. Chan School of Public Health earlier this month of a 1.4% fatality rate in confirmed cases.

The British group said the fatality rate among all of those infected with the new coronavirus — including those who don’t have symptoms — is 0.66%. By comparison, that is more than 30 times greater than the death rate for the H1N1 influenza, the cause of a 2009 pandemic, which was 0.02%.

The chance that a Covid-19 patient would develop symptoms severe enough to require hospitalization, especially for respiratory support, also rose sharply with age, Ferguson and his colleagues reported. In patients 80 and older, 18.4% did. While 12% of people in their 60s required hospitalization, 3.4% of 30-somethings and 1.1% of 20-somethings did. The sharpest difference came in late middle age: 4.3% of people 40 to 49 with Covid-19 required hospitalization, while 8.2% of 50-somethings did.

That is partly why the situation in Italy is so disastrous, with many hospitals overwhelmed by Covid-19 cases: The country’s median age (47) is the highest in Europe, and 23% of its people are 65 or older. Last week, doctors in Italy reported in the Journal of the American Medical Association that as of mid-March, 7.2% of Covid-19 patients had died. That might be partly explained by the high rates of infection among the elderly: 38% of Italy’s Covid-19 cases are in people 70 and older, compared to 12% in China.

The explanation for the generally heightened risk to the elderly, but also for the fact that Covid-19 kills many younger people even as some seniors survive, lies in a growing understanding of “immunosenescence.” Immunologists have identified some of the specific ways the immune system changes with age, allowing them to go beyond the simple assertion that it weakens.

“Older people are not as good at reacting to microorganisms they haven’t encountered before,” said physician and immunobiologist Janko Nikolich-Zugich of the University of Arizona College of Medicine. He calls it “the twilight of immunity.”

Our immune systems have two sets of defenses against viruses and other pathogens: a first-line army of cells, called leukocytes, that attack invading microbes within minutes to hours, and a second-line force of precisely targeted antibodies and T cells that surge to the battle front as late as several days after.

With advancing age, the body has fewer T cells, which produce virus-fighting chemicals. By puberty, the thymus is producing tenfold fewer T cells than it did in childhood, Nikolich-Zugich said; by age 40 or 50, there is another tenfold drop.

That leaves the body depleted of T cells that have not yet been programmed to defend against a specific microbe. Fewer such “naïve T cells” means fewer able to be deployed against a never-before-seen microbe.

“We just have fewer soldiers dealing with attackers we’ve never experienced before, like the new coronavirus,” Nikolich-Zugich said. (The body does retain the “memory T cells” that learned to fight attackers in youth, which is why immunization against smallpox and many other viral disease lasts decades.)

Another age-related change keeps T cells away from battle. Even before T cells enter the fray, other cells recognize invaders and dispatch natural killer cells and other soldiers to destroy as many as possible in the first few hours after infection. Then these same front-line cells literally show the virus to T cells, saying in essence, this is the enemy; produce virus-killing compounds.

“But this communication doesn’t work as well as we get older,” Nikolich-Zugich said. The instructor cells grow scarce and start to do the biological equivalent of mumbling. T cells therefore respond too late and too little.

Antibodies are made by B cells, and their decline is less precipitous than the fall-off in T cells. But old B cells, like old factories, can’t produce as much of their product — antibodies — as when they were new. Specifically, they have lower levels of the molecule that rearranges their genome so as to produce never-before-seen antibodies to a never-before-seen virus.

As if old age weren’t cruel enough, it brings one more change to the immune system: It slows down how quickly natural killer cells and other first responders hand off the defense to activated T cells and B cells. “This initial response remains in overdrive,” Nikolich-Zugich said. The core of that response is a fusillade of inflammatory molecules called cytokines.

That fusillade attacks the lungs and causes acute respiratory distress syndrome (ARDS), a common cause of Covid-19 deaths.

The cytokine barrage varies somewhat by sex, however. In a study published last month, Kuchel and colleagues showed that older men had, on average, more cytokine-producing cells than older women, who had more and better B cells and T cells.

That might explain the apparent, but still tentative, sex-based differences in the Covid-19 epidemic, with elderly men generally faring worse than elderly women. Hobbled B and T cells leave the body with fewer anti-coronavirus defenses.

Immunosenescence spells bad news if the new coronavirus continues to circulate, even at sub-pandemic rates, because it suggests that older people who have survived Covid-19 may not have robust immunity should they be exposed to the virus again.

With the flu, younger people have a stronger “immune memory” than older people — their T cells and B cells primed to attack if a flu virus they contracted decades ago returns. If immune memory for coronavirus resembles that for flu, Kuchel said, then “young people will be much more protected when it comes back.”

  • Has any link been established between Covid-19 and EVALI, other than the possible adverse effects of vaping in general?

  • A terrible thought keeps popping into my mind, based on what I have been reading about the various health systems around the world, and even the way attitudes have changed toward certain types of patients here in the US.
    My horrible question about the Covid death rate is, “Are all these people who are elderly or infirm dying DESPITE the best efforts of their local health system, or are they dying because that health system’s leaders just decided they weren’t worth saving?”

    • It is not a matter of writing them off, it’s not having the equipment we need, according to all accounts.

  • Most articles I have seen specifically about Covid-19 mention comorbidities. Older people, and particularly males in many countries, are more likely to have been smokers.

    How do the numbers change among lifelong never smoked?

  • Could that mean that those who have gotten flu shots (which takes up “naive” T-cells) over the years also more at risk to this virus?

    And to the person blaming “Boomers” for everything: thanks for showing how ignorant, petty and lacking thought those of your generation are. You’re a testament to the leftist/liberal Union guided education system in this country that fails to actually educate people to think an deduce and to our general failure to inspire morals and ethical thought and compassion to the children of the next generations.

    I’d say that’s our real failure we’ve raised people who can’t stand up and be strong just a bunch of whining adolescents.

  • So once again we sacrifice our future for baby boomers. This time as they attempt to live forever.

    • No, there is a lot of debt from the stimulus package but that benefits, primarily, people younger than boomers, who are already retired. I know it benefits business, maybe far too much, but businesses employ people who are not retired, either. The expenses for medical treatment of the sick are not the big part of this. The boomers are not ripping you off (in this case anyway)

  • In the data I have reviewed (and I believe also in the stats referenced above), the denominator used for calculating percentages is the number of cases in the population. During an outbreak this is a flawed method and tends to under-estimate the morbidity of the disease. The denominator should be the number of cases at some point in the past, based on the average number of days between infection and recovery (or death).

    • What you say sounds very logical, but the numbers of deaths/confirmed cases seems to be holding pretty steady at 2%. I did not expect that, but so far that is what I see, after several weeks of the epidemic. It’s very encouraging as I did not trust the Chinese numbers at all and thought they could be huge understatements, though 2% is actually very high if you think about it.

  • Is there any connection between having had a Spirochete infection (Lyme Disease etc.) and Covid19 resistance?

  • Unfortunately, there’s no mechanism suggested in this article that would not seem to apply equally well to the Spanish Flu, which killed predominantly people in their prime.

    • I have not kept up but the main theory ten years back was it was likely to provoke a cytokine storm. Use Wikipedia.

    • There are many, many factors that may explain the unusual age-specific morbidity and mortality that occurred during the 1918 influenza virus pandemic. Two come to mind:
      A.) The time span between the Russian Flu (1890) and the Spanish Flu 1918. The 20-somethings that succumbed to the Spanish Flu, had no/little exposure to influenza previously, thus their immune system did not recognize the new strain quickly enough (The Spanish flu was a very-very fast reproducing virus). Older people of the time had been exposed to influenza previously, and thus had the “pre-programming” immune defense to recognize the virus in time..

      B.) Among the bevy of vaccines that almost all children have been receiving for the past 40 years, is of course, an influenza vaccine. This exposes the immune system to generic influenza virus, helping to create the mentioned memory defense, and was not available during the 1918 outbreak.

  • There is no question that innate immunity to viruses and bacteria generally declines with age, and that this trend goes far to explain the greater mortality rate of older people after exposure to the COVID-19 virus. However, there is a fairly simple, yet very effective measure that can be taken to reverse or at least significantly ameliorate this age-related problem, including vulnerability to coronavirus infections. See this landmark study published by the American Journal of Clinical Nutrition in 2007: https://academic.oup.com/ajcn/article/85/3/837/4633003 (Zinc supplementation decreases incidence of infections in the elderly). Those especially interested in this approach to maintaining immunological health in during the COVID-19 pandemic can learn about the biological mechanisms concerned with regard to this particular virus in these two additional articles: https://www.vox.com/2020/3/26/21195347/coronavirus-covid-19-symptoms-reset-podcast (How the coronavirus works inside your body) and https://www.ncbi.nlm.nih.gov/pubmed/15140896 (Furin inhibition by compounds of copper and zinc). By the way, note that the HIV and anti-malarial drugs currently being considered or used speculatively as possible inhibitors of COVID-19 infection are suspected to all work by — one way or the other — inhibiting COVID-19 replication activity inside human cells. Zinc (and copper) supplements, however, can be obtained without prescription and are not (currently) in short supply.

  • Good article. Scary if you’re 62 and already missing a kidney, as I am, but there is also hope in the numbers. If millions have it or have had it, then it’s not as deadly as people have been saying. Nowhere near. Testing in Iceland shows that an order of magnitude more people may have been infected or currently have it, thereby driving overall mortality down even more–I’ve read as low as .06%. I’m hoping that study is correct.

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