New Analysis Reveals There May Be A Gene Behind Long Covid

It’s a mysterious constellation of symptoms — brain fog, fatigue, heart palpitation, and others — that bind together those living with long Covid. It’s estimated 65 million or more people around the world are experiencing this complex yet poorly understood condition.

In the U.S. alone, around 10 percent of adults infected with SARS-Cov-2, particularly the omicron variant, develop long Covid. Some surveys suggest that with omicron, long-haul cases may be on the decline. It still doesn’t change the fact that risk factors for the virus’ enduring aftermath remain murky.

According to a preprint published in medRxiv in July, genetics may play a role, particularly a version of a gene called FOXP4, which is active in both lung and immune cells. The study found that individuals who carried FOXP4 variants had about a 1.6-fold higher odds of developing long Covid. It doesn’t entirely explain the disparate symptoms of long Covid nor its root cause — severe infection remains a crucial risk factor. But the preliminary findings add to the genetic pantheon underlying Covid-19 resilience and vulnerability.

The study, which was a spin-off from research conducted by the global Covid-19 Host Genetics Initiative, looked at data from 24 other studies where data was collected from 6,450 people with long Covid across 16 countries. The genetics of these individuals were compared against one million others who did not develop long Covid. Among the genes that stuck out was FOXP4, a protein known as a transcription factor that’s responsible for regulating other genes. While this gene variant has been implicated as a risk factor for severe Covid-19 (as well as for lung cancer), the researchers found its association with long Covid risk was far too large to be explained by severe Covid-19 infection alone.

“This variant has a much stronger impact on long COVID than its impact on severity,” Hugo Zeberg, lead author of the preprint and assistant professor at the Karolinska Institutet, told Nature News in July.

The researchers also found this FOXP4 variant was highly expressed in lung cells. Carrying this gene could explain why many Covid long haulers grapple with respiratory issues, but it doesn’t explain other symptoms elsewhere in the body like brain fog or fatigue. It’s also important to bear in mind that since this is an association study, it doesn’t imply causation; further research is needed to determine that. Experts say that this is just one piece in a very large susceptibility jigsaw puzzle.

The new research hints at "some underlying immune dysregulation in the lung itself," Jill Hollenbach, an immunologist at the University of California, San Franciso, told NPR, which is contributing to persisting symptoms. "We need to just continue to follow these breadcrumbs and see where they lead us."