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ONE of the scariest mysteries of Covid-19 is why some people are mildly ill or have no symptoms and others die quickly, and scientists are beginning to figure out why.
An international team of researchers found that in some people with severe Covid-19, the body becomes dishonest, attacking one of its own key immune defenses rather than fighting the coronavirus. The majority were men, which helps explain why the virus affects men more than women.
And separate research suggests that children do better than adults because of robust “first responder” immune cells that decline with age.
They are the latest in a list of studies uncovering multiple features of the immune system’s intricate cascade that can tip the balance between a good or a bad outcome. Next: find out if all these new leads could offer much-needed ways to intervene.
“We have the knowledge and the ability to really boost many aspects of the immune system. But we shouldn’t use the mallet, ”warned Dr. Betsy Herold of the Albert Einstein School of Medicine in New York, a co-author of the children’s study.
In addition to complexity, people’s wildly variable reactions also reflect other factors, such as how healthy they were at first and how much of the virus, the “dose,” they were exposed to.
“Infection and what happens after infection is very dynamic,” said Alessandro Sette, a researcher at the La Jolla Institute for Immunology in San Diego, who is studying another part of the immune response.
Immune primer
There are two main arms of the immune system. Innate immunity is the body’s first line of defense. As soon as the body detects a foreign intruder, key molecules like interferons and cytokines that cause inflammation launch a wide-ranging attack.
Innate immune cells also alert the slower-acting “adaptive” arm of the immune system, the germ-specific snipers, to prepare. B cells begin to produce antibodies that fight viruses, proteins get so much attention in the search for vaccines.
But antibodies are not the whole story. The many other ingredients of adaptive immunity include “killer” T cells that destroy virus-infected cells, and “memory” T and B cells that recall an infection so they can kick in faster if they encounter that germ again.
A missing piece
Generally, when a virus invades a cell, proteins called type I interferons go into action and defend the cell by interfering with viral growth. But new research shows that those crucial molecules were essentially absent in a subset of people with severe Covid-19.
An international project discovered two reasons. In the blood of nearly 1,000 seriously ill Covid-19 patients, researchers found that 1 in 10 had what are called autoantibodies – antibodies that mistakenly target necessary virus fighters. Especially surprising, autoimmune disorders tend to be more common in women, but 95 percent of these Covid-19 patients were men.
The researchers did not find the harmful molecules in patients with mild or asymptomatic Covid-19.
In another 660 seriously ill patients, the same team found that 3.5 percent had genetic mutations that did not produce type I interferons.
Each of those silent vulnerabilities was enough to tip the scales in favor of the virus early on, said Dr. Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University in New York, who co-leads the Covid Human Genetic Endeavor. He is paid by the Howard Hughes Medical Institute, which also helps fund The Associated Press Department of Health and Science.
Certain interferons are used as drugs and are being studied as a possible treatment with Covid-19; the discovery of autoantibodies adds another factor to consider.
Children’s immunity accelerates rapidly
It is not clear why children appear to be at less risk from Covid-19. But occasionally they are sick enough to be hospitalized, giving Herold’s team the opportunity to compare 60 adults and 65 children and adolescents in New York’s Montefiore Health System.
Children produced much higher levels of certain cytokines that are among the first responders of the innate immune system. When the next stage of the immune system began, both adults and children produced antibodies directed against the coronavirus. Here’s the catch: The adult adaptive immune response was more of the type that can trigger an exaggerated inflammatory reaction.
The findings suggest that children’s early and robust reaction allows their immune systems to get ahead of the virus, making an overreaction less likely “and that protects them,” Herold said.
Any pre-existing immunity?
The coronavirus that causes Covid-19 is new to humans. But Sette’s team studied blood samples that were stored in freezers before the pandemic and found some housed memory T cells that recognized a small portion of the new virus in laboratory tests.
“In fact, it can be said that it is an experienced T cell. This has been the subject of combat before, ”Sette said. Researchers in Germany, Great Britain, and other countries have made similar findings.
The new coronavirus has cousins that cause up to 30 percent of common colds, so researchers believe those T cells could be remnants of past colds.
But despite speculation, “we still don’t know” that having those T cells makes any difference to who gets seriously ill with Covid-19, said Rory de Vries, a co-author of a study in the Netherlands that also found such T cells in old blood.
All of these findings call for a deeper understanding of the myriad ways that some people may be more susceptible than others.
“We need to look quite broadly and not draw premature conclusions about any particular facet of the immune system,” said Bali Pulendran, an immunologist at Stanford University. He’s also found some “hibernating” innate immune cells in seriously ill adults, and then he’s looking for differences before and after people get sick.
But, “it’s not just about the immune system,” said Dr. Anita McElroy, a viral immunity expert at the University of Pittsburgh who is closely following the research. A way to know in advance who is most at risk? “We are very, very far from that.” (AP)
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