Mild to severe: Immune system holds clues to virus reaction
(AP) — One of COVID-19’s scariest mysteries is why some people are mildly ill or have no symptoms and others rapidly die — and scientists are starting to unravel why.
An international team of researchers found that in some people with severe COVID-19, the body goes rogue and attacks one of its own key immune defenses instead of fighting the coronavirus. Most were men, helping to explain why the virus is hitting men harder than women.
And separate research suggests that children fare better than adults thanks to robust “first responder” immune cells that wane with age.
They’re the latest in a list of studies uncovering multiple features of the immune system’s intricate cascade that can tip the scales between a good or bad outcome. Next up: Figuring out if all these new clues might offer much-needed ways to intervene.
“We have the knowledge and capability of really boosting many aspects of the immune system. But we need to not use the sledge hammer,” cautioned Dr. Betsy Herold of New York’s Albert Einstein College of Medicine, who co-authored the child study.
Adding to the complexity, people’s wildly varying reactions also reflect other factors, such as how healthy they were to begin with and how much of the virus — the “dose” — 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, who is studying yet another piece of the immune response.
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, such as interferons and inflammation-causing cytokines, launch a wide-ranging attack.
Innate immune cells also alert the slower-acting “adaptive” arm of the immune system, the germ-specific sharpshooters, to gear up. B cells start producing virus-fighting antibodies, the proteins getting so much attention in the vaccine hunt.
But antibodies aren’t the whole story. Adaptive immunity’s many other ingredients include “killer” T cells that destroy virus-infected cells — and “memory” T and B cells that remember an infection so they spring into action quicker if they encounter that germ again.
A missing piece
Usually when a virus invades a cell, proteins called Type I interferons spring into action, defending the cell by interfering with viral growth. But new research shows those crucial molecules were essentially absent in a subset of people with severe COVID-19.
An international project uncovered two reasons. In blood from nearly 1,000 severe COVID-19 patients, researchers found 1 in 10 had what are called auto-antibodies — antibodies that mistakenly attack those needed virus fighters. Especially surprising, autoimmune disorders tend to be more common in women — but 95% of these COVID-19 patients were men.
The researchers didn’t find the damaging molecules in patients with mild or asymptomatic COVID-19.
In another 660 severely ill patients, the same team found 3.5% had gene mutations that didn’t produce Type I interferons.
Each of those silent vulnerabilities was enough to tip the balance 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 Effort. He is paid by the Howard Hughes Medical Institute, which also helps fund The Associated Press Health and Science Department.
Certain interferons are used as medicines and are under study as a possible COVID-19 treatment; the auto-antibody discovery adds another factor to consider.