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.
