In a new study, researchers found two new mutations in the TLR7 gene in healthy young men who became seriously ill with severe Covid-19.
It’s becoming more plausible that such mutations undermine a sufficient immune response against SARS-CoV-2.
An infection with SARS-CoV-2 can lead to serious inflammation and even death in some individuals. Older age, male gender and chronic diseases such as diabetes and obesity increase the risk for a severe outcome.
But these risk factors cannot explain why (very) severe Covid-19 also occurs in young, healthy men without a medical history.
Last year researchers found for the first time that mutations in the TLR7 gene were a possible rare genetic risk factor. Two unrelated pairs of brothers became seriously ill with Covid-19 and one of them died, they reported.
They all had a mutation in the TLR7 gene, which encodes the receptor that plays a role in the recognition of the coronavirus and initiates the antiviral immune response through induction of interferons.
TLR7 thus appears to be an important factor in the defense against SARS-CoV-2.
An Italian study of men over 60 years of age with severe COVID-19 found that more than 2 percent of severely affected men carried a genetic mutation in TLR7, leading to an impaired functioning TLR7 receptor.
A recent study, which looked for rare genetic risk factors through an association study in more than half a million people, also found TLR7 as the most important factor for severe Covid-19.
In the study, the team screened 14 cases of severe Covid-19 in young, healthy men under the age of fifty.
They found the TLR7 gene in both a Spanish and a Dutch patient. What made the Dutch case special is two of the patient’s cousins had the same mutation.
Although they were not yet eligible for vaccination at that time due to their young age, they were given priority based on the research.
The team says mutations in the TLR7 gene are now also listed as an immune deficiency in OMIM – the international website where such information is registered.
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The study is published in Frontiers in Immunology.
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