Lung Gene FOXP4 Linked to Long COVID

A recent study, published in Nature Genetics, looked at the genetic information of many people from different parts of the world to see if inherited differences play a role in Long COVID.

• The study used a method called Genome-Wide Association Study (GWAS). 
• This method scans our DNA for tiny “spelling mistakes” (called single-nucleotide polymorphisms or SNPs) that are more common in people with a certain condition.

What is Long COVID?

• Long COVID refers to symptoms that persist for weeks or months after recovering from COVID-19.
• According to the World Health Organization (WHO), the most common Long COVID symptoms are fatigue, breathlessness and issues with mental focus. 
• As of now, there is no specific drug treatment for Long COVID.

The Key Finding: A Gene Linked to Long COVID Risk

• FOXP4 Gene Connection: The study found a strong link between Long COVID and a specific area on chromosome 6, which is near the FOXP4 gene.
• Specific Variant Identified: A particular variant in this region, called rs9367106, was found to increase the risk of Long COVID. People with the “C” version of this variant were about 63% more likely to have Long COVID symptoms.
• Not Just for Severe Cases: This FOXP4 gene increased Long COVID risk even in people who weren’t seriously ill or hospitalized, suggesting its effect isn’t only tied to how severe the initial infection was.
• Varying Across Populations: The frequency of this variant differed across different groups of people. For example, it was found in about 1.6% of non-Finnish Europeans but in up to 36% of East Asians.

What Does FOXP4 Do? From Lungs to Immunity

• Active in Lung Tissue: The genetic variant linked to Long COVID is in a part of DNA that is very “active” in lung tissue. This suggests it might affect how the lungs work.
• Impact on Lung Cells: FOXP4 is highly active in type 2 alveolar cells in the lungs. These cells are crucial for keeping air sacs open, clearing fluids, and repairing damaged tissue. They also play a role in how the immune system responds to viruses like SARS-CoV-2.
• Higher FOXP4 Levels, Higher Risk: Researchers also found that people with moderately higher levels of FOXP4 in their blood (even after the initial infection cleared) were more than twice as likely to develop Long COVID. 

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