Researchers have found that a defect in a gene may put even young people at risk of severe COVID-19 complications.
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Current observations suggest that the coronavirus SARS-CoV-2 causes severe symptoms mainly in elderly patients with chronic disease. However when two pairs of previously healthy young brothers from two families required mechanical ventilation at the intensive care unit in rapid succession, doctors and researchers at Radboud University Medical Centre in the Netherlands were inclined to consider that genetic factors had a key role in compromising their immune system.
Their research identified as the gene Toll-like receptor 7, or TLR7, plays an essential role in the defence against SARS-CoV-2. The finding, published in the journal JAMA, has potential major consequences for understanding and possibly treatment of COVID-19. During the wave of COVID-19 patients that flooded Dutch hospitals in the first half of 2020, two young brothers became seriously ill with the SARS-CoV-2 virus and had to be mechanically ventilated in the ICU.
One of them died from the consequences of the infection, the other recovered. The severe course of disease in otherwise healthy young brothers was a relatively rare occurrence, especially because the virus mainly affects the elderly. "In such a case, you immediately wonder whether genetic factors could play a role," said geneticist Alexander Hoischen, one of the co-authors of the study.
That search quickly revealed mutations in the gene encoding for TLR7. "TLR7 function has so far never been associated with an inborn error of immunity. But unexpectedly we now have an indication that TLR7 is essential for protection from this coronavirus," Hoischen said. "So it seems that the virus can replicate undisturbed because the immune system does not get a message that the virus has invaded."
Then, quite unexpectedly, the doctors and researchers at Radboudumc came across another pair of brothers who have fallen seriously ill with COVID-19. Again, they are both under 35 years of age. Both of them were also in the ICU for mechanical ventilation. "Then the question of the role of genetics became even more obvious," said Hoischen. "Suddenly we had four young people with a defect in the same gene, all of whom had fallen seriously ill from the SARS-CoV-2 virus." "This discovery not only provides us with more insight into the fundamental workings of the immune system, but it may also have important consequences for the treatment of severely ill COVID-19 patients," said Frank van de Veerdonk, immunologist and infectiologist.
