Researchers at Radboud university medical center in Nijmegen have discovered a defect in the genetic code of a number of corona patients, which explains why some young people become seriously ill from the coronavirus. They hope that other severely ill young corona patients can be treated better with the help of the new insights.
The researchers discovered the role of the TLR7 gene when a Maastricht UMC + doctor noted that two young brothers were seriously ill from Covid-19 and had to go on a ventilator. One of them died from the effects of the disease, the other recovered. It is exceptional that young people get sick from corona, most of them only have mild complaints.
“In such a case, you immediately wonder whether genetic factors are involved,” says geneticist Alexander Hoischen of Radboud university medical center. “That two brothers get so seriously ill may be a coincidence, but it is also possible that a birth defect played a role.”
Essential gene
The research team mapped part of the genes of the brothers, especially the genes that play a role in the immune system. Soon a gene on the X chromosome came into view: TLR7. That gene helps to recognize pathogens and activate the immune system. The two brothers were found to lack some letters in the genetic code.
The team concluded that the TLR7 gene is apparently essential to detect the coronavirus. Hoischen: “It seems that the virus can just go ahead because the immune system is not notified that the virus has invaded. That could be the reason for the serious course of the disease.”
Men are extra sensitive to the error in the genetic code. Women with two X chromosomes also have two copies of the TLR7 gene. Since men only have one, there is no second gene that can take over the role of the defective TLR7 as it does in women.
Two more brothers
During the study, the researchers unexpectedly had to deal with two more seriously ill brothers under 35 years of age who had to go to ventilator on the ICU. They recovered from the disease. They also found something wrong with the TLR7 gene. “This time we saw no loss of letters, but a single typo,” says Hoischen. “The effect is the same, because these brothers also make too little effective TLR7.”
The team also investigated what exactly the gene does when it is activated. It then produces interferons, special proteins that are essential in the defense against viral infections. These are especially important with corona, says Cas van der Made, a doctor in training at the department of internal medicine. “From the literature we know that this virus has tricks to reduce the production of interferons by immune cells.”
Tests showed that the immune cells of patients without properly functioning TLR7 hardly respond and that hardly any extra interferons were produced. The virus seemed to have free rein.
The discovery of the researchers at Raboudumc may help treat other critically ill corona patients. The substance interferon can be given to patients as therapy. It is currently being investigated whether this actually helps with treatment.
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