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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.”

  • I am 78 years old. I have vasculitus. I take methotrexate followed by folic acid two days later. will Coronavirus kill me?

  • My bet is lethality of Covid19 among the elderly is due to the same thing here as it is in Italy. Socialized medicine. Here in the U.S. folks on Medicare may wait two weeks for an appointment with their doctor, just like those on socialized medicine in Italy. By then all the doctor has to say is “you came in too late.”

    • Absolutely ridiculous. You will see in the coming months how far more people will be infected and die in the US than even Italy.

    • You lose, The U S is suffering far more because we have too many people like you in charge. Bent on mining human health like a gold mine while staring at an existential threat to entire human race. Are you incapable of insight?

    • Socialized medicine sounds pretty good then. The last time I tried to make an appointment with my doctor, the earliest appointment was 4 weeks out.

    • You are wrong. It is the lack of health insurance that keep patients from seeking out medical help. It is the lack of hospital and proper equipment that make it more difficult for physicians to help.
      And it is the lack of discipline of social distancing and confinement combined with the arrogance of thinking one is immune to contracting the disease that drives up the mortality rate.

  • Bedrest alone could increase vulnerability to the virus and raise the chances of pneumonia. All the adverse effects of bed rest are more severe in the elderly. Among them are metabolic dysfunction and diabetes, notably.

    It would be difficult for hospital staff to provide elderly patients opportunities to arise from bed and move around, or even to perform some exercises in bed, when working with multiple patients who are frail, sick and elderly. Elderly patients, being more susceptible than younger ones to the effects of painkillers, sedatives and hypnotics (which staff might administer for various reasons) might not be capable of arising in any event. In fact, the use of such drugs, and especially the use of tranquilizers knowns as “antipsychotics,” could be the real cause of death in any number of those over age 85. It is unfortunate that the easy transmissibility Covid-19 probably means that family members who could help prevent and diminish the bed-rest-induced and drug-induced problems that we know can worsen outcomes won’t be allowed to participate in the hospital care of their loved ones. That might change when there is an antibody test to identify family members who had already contracted and cleared the virus, knowingly or not.)

    I guess what I mean to say is that the death rate in elderly patients could probably be lower than it is. Shortcomings and errors in the care the elderly receive in hospitals, of the kind I have described here, can go on all day and night across the entire USA because they not regarded as instances of gross negligence or medical malpractice. Any doctor or nurse worth her or his salt should know or does know that bed rest and certain drugs are potentially lethal to the frail elderly.

    References
    The physiological consequences of bed rest. Journal of Exercise Physiology. Volume 10 Number 3 June 2007
    https://cupola.gettysburg.edu/cgi/viewcontent.cgi?article=1029&context=healthfac

    Strax, T.E, et al. (2009). Physical modalities, therapeutic exercise, extended bedrest, and aging effects In S. Cuccurullo (Ed.), Physical Medicine and Rehabilitation Board Review (pp. 621-629). New York, New York: Springer Publishing Company.

  • This study takes into account only the population of patients, who are the people with the most severe symptoms, when epidemiologists say that most cases are with no or slight symptoms. Therefore all the death rates described here are grossly inflated.

    • Another thing, I hear people claim the great majority of people do not have any symptoms. That seems to be based on the CDC and public health people saying most people do not need hospital care.
      Well, those are not at all the same thing.
      I have not seen any numbers for how many people get infected and never know it, but it may be very small – the accounts of people who were sick vary a great deal – one guy said he had a high fever for about half a day then moderate. Other people say they were flat on their backs for days, and if they got up to go to the bathroom they were exhausted afterwards.
      I think the numbers of people who do not even know they are sick could be very low. Some may never get tested or even go to see a doctor, (Thank you for staying home) but that does not mean they are hidden from the public health system

  • What can be done by the elderly to strengthen their immune system. A friend sells something called Juice Plus. Could this help me? What about supplements and vitamins?

  • I read that some medical professionals were testing a thoery that using the vaccine for TB (Bacillus Calmette-Guérin) would help the immune system ramp up immunity production of (T & B cells?) to fight acute respiratory distress syndrome. As I was the first generation in the U.S. to not be given the small pox vaccine (1972) nor have I had the TB vaccine (Bacillus Calmette-Guérin). Is there any resulting evidence regarding the bodies defense to COVID-19 with a recent TB vaccine? As immunizations of these vaccines are clearly delineated based upon certain country recommendations ( I understand Mexico still gives Bacillus Calmette-Guérin for TB ) and age is there any possible links?

  • It appears the reason that kids don’t become seriously ill with coronavirus is because it is primarily an enteric disease in children (link below). Like the oral vaccine for polio, a subclinical intestinal infection stimulates production of antibodies that in turn protect against a devastating systemic disease.

    That’s a theory, not a fact, but it seems worthwhile to explore the possibility of an oral vaccine for coronavirus in conjunction with development an injectable vaccine. The latter will take at least 18 months and possibly longer. We can test the efficacy of an oral vaccine right now by encapsulating the virulent virus and administering it orally to selected brave young volunteers, e.g. soldiers.

    Title: Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nature Medicine (2020)

    Abstract: We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal–oral transmission.

    https://www.nature.com/articles/s41591-020-0817-4

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