During the COVID-19 pandemic in the first half of 2020, two young brothers in Holland became seriously ill with the virus
In this case, you immediately wonder,whether genetic factors might play a role. Getting sick from an infection is always an interaction between the virus and the human immune system. It may be a coincidence that two brothers from the same family are so seriously ill. But it is also possible that a congenital error in the immune system played an important role. We investigated this possibility ..
Geneticist Alexander Khoishen
All of both brothers' genes were sequenced, and the researchers then examined the data for a possible common cause.
Scientists have primarily studied genes that play a role in the immune system. They knew that some of these genes are located on the X chromosome.
This search quickly revealed mutations in the gene,encoding Toll-like receptor 7, TLR7 for short. There are many TLR genes that belong to a family of receptors that play an important role in recognizing pathogens (such as bacteria and viruses) and activating the immune system.
Several letters were missing from the genetic codegene TLR7. As a result, the code cannot be read properly and the TLR7 protein is unlikely to be produced. Until now, TLR7 function has never been associated with an innate immunity error. But unexpectedly, scientists now have a sign that TLR7 is needed to protect against the new coronavirus. Thus, the virus can replicate without interference - the immune system does not receive a message that the virus has invaded. Because TLR7, which is supposed to identify the attacker and subsequently activate the protection, is hardly present. This may be the reason for the severity of the disease in two brothers.
Then, quite unexpectedly, doctors andresearchers at Radboudumc encountered another pair of brothers who became seriously ill with COVID-19. Again, the age of patients is up to 35 years. Both of them were also in the intensive care unit for mechanical ventilation. Then the question of the role of genetics became even more obvious, scientists emphasize. They also examined the genetic code of these two brothers. This time they saw no errors in the TRL7 gene. However, the effect on the gene was similar - these brothers also do not produce enough functional TLR 7 protein.
Scientists have investigated the consequences of improper functioning of the TLR7 receptor.
Once activated, TLR7 triggers production like this:called interferons, signaling proteins that are essential for protection against viral infections. This immune response is perhaps even more important in the fight against the SARS-CoV-2 virus. There is evidence that the virus has the ability to reduce the production of interferons by immune cells. This abnormality in the gene may actually “turn off” protection from COVID-19.
Scientists emphasize that this is a very specificthe abnormality is an immunodeficiency that is mainly associated with the new coronavirus. None of the four men had previously suffered from immune-related diseases.
The discovery not only gives scientists a deeper understanding of the basic principles of the immune system, but it could also have important implications for the treatment of critically ill COVID-19 patients.
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