Mild to Severe: The immune system retains clues to the viral response

Another study suggests that children are better than adults because of the powerful “first responder” immune cells that decline with age.

They are the latest in a list of studies that characterize multiple features of the complex cascade of the immune system and can tilt the scale between good and bad results. Next Step: Consider whether all these new clues provide a highly needed intervention method.

“We have the knowledge and ability to really support many aspects of the immune system, but we don’t have to use a sledgehammer,” said Betsy of Albert Einstein Medical College in New York, who co-authored the study of children. Dr. Herold warned.

In addition to complexity, people’s changing reactions also reflect other factors such as how healthy they were initially and the amount of virus they were exposed to (“dose”).

“It’s very dynamic to be infected and what happens after infection,” said Alessandro Sette, a researcher at the Lahora Institute of Immunology in San Diego, who is studying yet another part of the immune response.

The immune system has two main arms. Innate immunity is the body’s first line of defense. As soon as the body detects a foreign invader, important molecules such as interferon and inflammatory cytokines launch a widespread attack.

Innate immune cells also warn bacterial-specific snipers, the slow-acting “adaptive” arm of the immune system, to be ready. B cells have begun to produce antibodies that fight the virus, and proteins have received a lot of attention in vaccine hunting.

But antibodies are not everything. Many other elements of adaptive immunity include “killer” T cells, which destroy virus-infected cells, and “memory” T cells and B cells, which remember the infection.

Normally, when a virus invades a cell, a protein called type I interferon acts to protect the cell by blocking the growth of the virus. However, new studies show that these important molecules were essentially absent in a subset of people with severe COVID-19.

The international project has revealed two reasons. In the blood of about 1,000 patients with severe COVID-19, researchers found that 1 in 10 had what was called an autoantibody. This is an antibody that accidentally attacks the required virus fighter. Especially surprisingly, autoimmune diseases tend to be more common in women, but 95% of these COVID-19 patients were men.

The researchers found no molecules harmful to patients with mild or asymptomatic COVID-19.

In another 660 critically ill patients, the same team found that 3.5% had a gene mutation that did not produce type I interferon.

Dr. Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University in New York, co-leader of COVID Human Genetic Effort, said that each of these silent vulnerabilities was sufficient to quickly balance the virus. Said that.

Certain interferons are used as pharmaceuticals and are being studied as a potential treatment for COVID-19. The discovery of autoantibodies adds another factor to consider.

Kids’ immunity is fast

It is not clear why children appear to be at low risk for COVID-19. But sometimes they are ill enough to be hospitalized, giving the Herold team the opportunity to compare 60 adults, 65 children and teens at the Montefiore Health System in New York.

Children produced much higher levels of certain cytokines, one of the first responders to the innate immune system. When the next stage of the immune system began, both adults and children made antibodies that targeted the coronavirus. Here’s the rubbing: The adaptive immune response in adults was the type that could cause an inflammatory hyperreactivity.

Findings suggest that a strong early reaction in children puts their immune system ahead of the virus, reducing the likelihood of overreaction and “it protects them,” Herold said. Said.

Do you have existing immunity?

The coronavirus that causes COVID-19 is new to humans. However, Sette’s team studied blood samples stored in the freezer prior to the pandemic and found some hidden memory T cells that recognized a small portion of the new virus in laboratory tests. ..

“It really turns out that this is an experienced T cell. I’ve seen it in combat before,” Sette said. Researchers in Germany, the United Kingdom and other countries have made similar discoveries.

Researchers believe that these T cells may be the remnants of past colds, as the new coronavirus contains cousins ​​that cause 30% of the common colds.

However, despite speculation, “I don’t know yet” that having these T cells makes a difference to those who get seriously ill with COVID-19, says Rory, co-author of a study in the Netherlands. deVries says. Old blood cells.

The results of all these findings call for a deeper understanding of the myriad of ways that some people are more susceptible than others.

Stanford University immunologist Bali Plendran said: “We look very broadly at certain aspects of the immune system and do not dive into premature conclusions. He also discovered some innate immune cells in a” hibernating state “in a seriously ill adult, and then: Looking for differences before and after people get sick.

But “it’s not just the immune system,” warned Dr. Anita McElroy, a viral immune expert at the University of Pittsburgh Medical Center, who is closely watching the study. How to know in advance who is most at risk? “We have a long way to go.”

The Associated Press’s Department of Health Sciences is supported by the Department of Science Education at Howard Hughes Medical Institute. AP is solely responsible for all content.

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