Mild to severe: immune system leads to virus response

One of the most frightening mysteries of COVID-19 is why some people are mildly ill or have no symptoms and others die rapidly – and scientists are beginning to reveal it.

An international team of researchers found that in some people with severe COVID-19, the body goes rogue and attacks its own key immune immunity rather than fighting coronovirus. Most were men, helping to explain why the virus is killing men more than women.

And separate research suggests that children age better than adults thanks to weak “first reaction” immune cells.

They are the latest in a list of studies highlighting many features of the complex cascade of the immune system that can tip the scales between good or bad results. Next: finding out if all these new clues can present much needed ways to intervene.

“We have the knowledge and ability to really boost many aspects of the immune system. But we don’t need to use a sledge hammer, “said Dr. Einstein College of Medicine, New York. Warned by Betsy Harold, who co-wrote the child’s study.

Adding to the complexity, people’s wildly different reactions also reflect other factors, such as how healthy they were and how many “doses” of the virus they were exposed to.

“Infection and what happens after infection is a very dynamic thing,” said Alessandro Sette, a researcher at the La Jolla Institute for Immunology in San Diego, which is studying another piece of the immune response.


The immune system has two main weapons. Inté immunity is the body’s first line of defense. As soon as the body detects an alien intruder, key molecules, such as interferons and inflammatory cytokines, launch a widespread attack.

Congenital immune cells alert the slow-acting immune system, the “adaptive” arm of germ-specific sharpshooters. B cells begin to produce virus-fighting antibodies, with the protein receiving so much attention in the vaccine hunt.

But antibodies are not the whole story. Many other components of adaptive immunity include “killer” T cells that destroy virus-infected cells – and “memory” T and B cells that miss an infection so that they act on encountering that germ again. Spring in Quicker

A missing pie

Typically when a virus attacks a cell, a protein called type I protects the cell by interfering with viral growth. But new research suggests that those important molecules were essentially absent in a subset of people with severe COVID-19.

An international project uncovered two reasons. In the blood of about 1,000 severe COVID-19 patients, researchers found that 1 in 10 are called auto-antibodies – antibodies that incorrectly attack those virus fighters. Especially surprising, autoimmune disorders are more common in women – but 95% of these COVID-19 patients were men.

Researchers did not find harmful molecules in 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.

Each of those silent vulnerabilities was enough to quickly strike a balance in favor of the virus, Dr. Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University in New York, who co-leads the COVID Human Genetic Effort. He is paid by the Howard Hughes Medical Institute, which also helps fund the Associated Press Health and Science Department.

Some interferons are used as drugs and studied as potential COVID-19 treatments; Auto-antibody adds another factor to consider.


It is unclear why children appear to be at low risk of COVID-19. But sometimes they are ill enough to be hospitalized, allowing Harold’s team to compare 60 adults and 65 children and teens in New York’s Montefor Health System.

Children produced high levels of certain cytokines that are among the first responders of the innate immune system. When the next phase of the immune system kicked off, both adults and children made antibodies targeting coronovirus. Here’s the rub: Adults had more of an adaptive immune response that could trigger an inflammatory overgrowth.

The findings suggest that the children’s initial strong reaction leads to their immune system overtaking the virus, making it less likely to overreact “and that it is protecting them,” Harold said.

Any practicality?

The coronovirus that causes COVID-19 is new to humans. But Sette’s team studied blood samples that were stored in the freezer before the epidemic and found some disturbing memory T cells that identified a small fraction of the new virus in laboratory tests.

“You can really tell that this is an experienced T cell. The match has been seen before. Researchers in Germany, Britain and other countries have drawn similar conclusions.

New coronoviruses have cousins ​​that cause up to 30% of the common cold, so researchers believe those T cells may contain remnants of a previous cold.

But despite the speculation, “we don’t yet know” that it makes a difference to have T cells that become seriously ill with COVID-19, said Rory de Vries, co-author of a study in the Netherlands Such T was also found in old blood cells.

All these findings beg for a deeper understanding of the myriad ways some people may be more sensitive than others.

“We don’t have to look very broadly and draw premature conclusions about a particular aspect of the immune system,” said Stanford University immunologist Bali Pullendran. They have found some sick immune cells “in a state of hibernation”, in critically ill adults and those looking for differences before and after the next sick.

But, “it’s not just about the immune system,” a viral immune specialist at the University of Pittsburgh, Dr. Warned Anita Maclero, who is watching the research closely. A way to tell in advance which is at risk? “We are a long, long way from that.”

The Associated Press Department of Health and Sciences has support from the Science Education Department of Howard Hughes Medical Institute. AP is solely responsible for all content.


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