Genetic or immune deficiencies can impair the ability to fight Covid-19. World news

Studies have found that a significant proportion of patients who develop the life-threatening form of Covid-19 have a genetic or immunological defect that impairs their ability to fight the virus.

In a paper published in Science magazine, Covid’s human genetic efforts The International Consortium describes two deficiencies in severe Covid-19 patients that prevent them from making a front-line immune molecule called type 1 interferon.

Patients would have carried these glitches for years before the pandemic, or in the case of genetic errors, their entire life. The findings may help explain the mystery surrounding the coronavirus: why it causes some patients to become ill or die from intensive care, while others remain largely unaffected or asymptomatic. Is there?

The consortium sequenced all or part of the genomes of 659 severely ill Covid-19 patients worldwide and 534 genomes of asymptomatic or mild infections. I found it Severely ill patients were more likely to carry types of mutations that could not make interferon. Such mutations are rare, but collectively occur in 3.5% of severe cases.

In Second studyThey involved nearly 1,000 severe Covid-19 patients and found that 1 in 10 patients had antibodies to their interferon. No such autoantibodies were found in asymptomatic or mild patients. It was also detected in only a small proportion (0.3%) of healthy controls. These findings were described by a scientist as “amazing.”

According to Jean-Laurent Casanova, an immunologist at Rockefeller University in New York City, and Neckar Hospital for sick children in Paris, these two types of errors account for about 15% of life-threatening Covid-19 cases. I will. Conduct the consortium.

Casanova suspects that human genetics will explain most of such cases. This is because the consortium has only searched for 13 mutations in 300 odd type 1 interferon-related genes so far, so it is already a large-scale project. Many other genes, including genes that are not related to interferon, can affect a person’s response to the virus.

Type 1 interferon is a molecule produced by the immune system as soon as an infection is detected. It works by stopping virus replication. If this front-line defense is effective, one will not even feel sick. If not, it spends the body’s time involving antibodies and immune cells to initiate an immune response that targets the virus in question.

Without interferon, critically ill Covid-19 patients rely solely on this second defense mechanism. This can take several days to reach full strength. The Sars-CoV-2 virus can make a good start from damage to body tissues.

Casanova said the discovery of a congenital genetic error in critically ill patients with Covid-19 happened by accident. “Thanks to a 2-year-old girl from Angers, France.”

The infant appeared in the Neckar intensive care unit in 2011 with a life-threatening flu. The doctor saved her life, but wonders why she couldn’t dodge the infection like most children, Casanova sequence From her genome, she was found to have two copies of the recessive genetic trait. This means she couldn’t make interferon. She has been vaccinated against the flu every year and since then she has prospered because her antibodies function normally.

The discovery of autoantibodies is especially exciting. As 95% of critically ill patients with autoantibodies are men over the age of 50, Vanessa Sancho Shimizu, a consortium member and infectious disease doctor at Imperial College London, said: Gender bias in a serious patient population, “she says.

It is not clear why those patients have such antibodies, but the cause may be hereditary. Another mystery is why patients with genetic errors survived previous infections, and researchers have a theory about this. “Influenza,” said Sancho Shimizu.

Steven Chapman, a pulmonologist at the Welcome Human Genetics Center in Oxford, who was not involved in the study, said the paper contributed significantly to explaining why the severity of the disease varies dramatically between individuals. He said he did. Regarding the discovery of autoantibodies, he said: “If this is true, it’s a surprising result.”

Patients who arrive at the hospital and are diagnosed with positive autoantibodies can undergo plasmapheresis to remove these antibodies from their blood, which should guide their diagnosis and treatment. These patients may also benefit from treatment because autoantibodies save one particular form of interferon (beta form). Inhaled interferon beta..

Magnus Gott Fresson, an infectious disease specialist at the University of Iceland, said the results draw attention to those conducting clinical trials of convalescent plasma.