Why is COVID-19 deadly for some and not for others? Scientists have discovered other mechanisms responsible for the course of the infection

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Among the million deaths of the coronavirus, there were those who, by all rules of probability, should be infected mildly or even asymptomatically. Meanwhile, young, healthy and strong people were ill as badly as the elderly, burdened with numerous comorbidities. So what determines the severity of COVID-19 symptoms?

1. Over 10 percent of people produce antibodies that attack their own interferons
2. Interference with type I interferons can be treated with known drugs
3. A team of COVID Human Genetic Effort scientists has identified an antibody that neutralizes one or more IFN proteins
4. 94 percent of patients with IFN-neutralizing antibodies found were male
5. There were 13 abnormalities responsible for the anti-influenza activity in IFN gene sequences
6. More information about the coronavirus can be found on the TvoiLokony home page

Recently, we have two studies, the authors of which have attempted to identify the mechanisms of the immune system responsible for the deadly end of the disease. By the way, they also solved the mystery of the greater risk of a severe course of infection in men.

Coronavirus: The immune system attacks the interferons, preventing them from working

Both studies indicate that type I interferons (IFNs) play a significant role in the course of COVID-19. IFN are proteins produced by infected cells to help stop infection. However, there are people for whom they don’t work. The first study found that more than 10 percent of healthy people who develop severe COVID-19 symptoms produce antibodies that attack their own IFN, preventing them from fighting the virus.

The second looked at patients hospitalized for severe infection – some were in their 20s – and found at least 3,5 percent to have genetic mutations that prevent IFN from working properly. While the discovery of this mechanism explains only some of the most serious cases of COVID-19, it could save tens, if not hundreds, of thousands of lives.

These findings provide convincing evidence that type I interferons are a common cause of the life-threatening course of COVID-19, said Dr. Jean-Laurent Casanova, head of St. Giles Laboratory of Human Genetics of Infectious Diseases at Rockefeller University. “Or at least in theory, they could be treated with existing medications.

Working with a large international team of scientists as part of the COVID Human Genetic Effort project, Dr. Casanova has identified an antibody that neutralizes one or more IFN proteins. He found them in 101 out of 987 COVID-19 patients (10,2%).

This is not the first time that we discover that the immune system attacks interferons, preventing them from working properly. Some bacterial infections, such as those caused by staphylococci, worsen when the antibodies produced in the body turn against their own interferons. A similar type of sabotage has been observed in people treated with interferon for hepatitis, as well as in women with lupus. The discovery would explain one of the most dangerous symptoms of COVID, pointing not only to treatments, but also the possibility of identifying those most at risk. By the way, another puzzle is also solved.

Genetic mutations in interferon cells can inactivate them

“Interestingly, 94 percent of the patients with IFN-neutralizing antibodies were male, which explains why they are more susceptible to severe COVID-19,” said COVID Human Genomic Effort team member Dr. Stuart Tangye.

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In one of the studies discussed, it was shown that even defective genes secreted by interferon cells act to the detriment of the patient. They were compared in 659 patients with severe COVID-19 and 534 who had mild or asymptomatic infections. 13 abnormalities were found in the sequences responsible for the anti-influenza activity of IFN. Deactivating mutations were noticed in only 23 patients, i.e. about 3,5%, but disruption of the key immune pathway can have fatal consequences even for a small part of the population.

— The way SARS-CoV-2 affects humans is puzzling. The virus can cause an asymptomatic infection or kill you within days Says Professor John Christodoulo, a geneticist at the Murdoch Children’s Research Institute in Australia. Disruptions in the production of type I interferon reduce the ability of patients to protect themselves from COVID-19 infection.

The combination of the results of both studies creates a solution to one of the coronavirus mysteries, explaining why it is so unpredictable. While the scientists’ recent discoveries are significant, it is hard not to mention the huge number of deceased who were in good health, believing that they belonged to a group that was safe from anything.

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