The Long Covid FOXP4 mutations are 7x more common in Finnish people than in non-Finnish Europeans, and 36x more common in East Asians
IS THERE A LONG COVID GENE?
Yes. There is at least one Long Covid gene. And we now know what it is.
In a pre-print study released last week, The COVID-19 Host Genetics Initiative (HGI) made the astonishing announcement that they’ve identified a gene mutation common in people with Long Covid that isn’t common in people without Long Covid.
The study, called “Genome-Wide Association Study of Long Covid,” analyzed the genes of 6,450 Long Covid patients and 1,093,995 population controls (people without Long Covid) from 24 studies across 16 countries.
They found a strong association with Long Covid and mutations to a single gene. But before we get to that, let’s review a few of the things we’re talking about.
WHAT IS LONG COVID?
Long Covid is a debilitating disease some people get after they’ve had Covid-19.
It is not a continuation of Covid-19.
It is not a slow recovery from Covid-19.
It is not imaginary.
It is not just feeling a little tired.
It is a new, horrific disease that has been shown to impact every part of the body. Contrary to misinformation often repeated in the media, most people who go on to develop Long Covid did not have severe Covid-19.
In the same way the Epstein Barr Virus causes mononucleosis in the acute phase and can later cause Multiple Sclerosis in some people, the SARS-COV-2 virus causes Covid-19 in the acute phase, and can later cause Long Covid - in some people.
Long Covid has left millions of people disabled and unable to function in everyday life. We don’t yet know how Long Covid will ultimately impact life expectancy, but we do know life insurance companies have begun denying coverage to people with Long Covid - which can’t be good.
The Centers for Disease Control in the United States says one in five people infected with SARS-COV-2 will go on to develop Long Covid. Research from the University of Hong Kong puts that number closer to a staggering 7 in 10 people.
There are no official treatments for Long Covid, and few politicians or corporate media outlets seem willing to talk about it at all.
WHAT IS A GENE, ANYWAY?
A gene is a tiny part of our body's instructions that tells our bodies how to grow and function. It's made of a material called DNA and carries the information that determines our traits, like our eye color or height.
You have a copy of this genetic blueprint for “you” in every cell in your body. Genes are passed from parents to children and are responsible for the similarities and differences we see among individuals. They’re also responsible for how our bodies work - or don’t work.
There are between 20,000 and 25,000 genes in a human body, and with the exception of identical twins, no two people’s combinations of genes are exactly alike.
WHAT’S THE LONG COVID GENE CALLED?
The gene associated with Long Covid is called FOXP4.
The FOXP4 gene is located on human chromosome 6, and it has a very important job, called transcription. Transcription is when a gene basically “writes” instructions telling other genes what to do.
FOXP4 is writes instructions for the formation of blood vessels, the brain and the central nervous system. It’s also important in fostering regulation and repair of these tissues.
If there is a mutation in the gene, these things (or other things) might not happen properly.
WHAT IS A MUTATION?
Gene mutations, also called “alelles,” are small changes in a gene’s “sequence.” Genes are like words. They’re made up of “letters,” arranged in different orders. In gene mutations, one or several of those “letters” are out of place.
People with Long Covid have mutations in the FOXP4 gene that change the way FOXP4 writes instructions for other genes. The other genes then end up making proteins differently than they should, and sometimes this causes disease.
In fact, even before this Long Covid study, FOXP4 mutations have been associated with a host of diseases and health problems, including some we are seeing in people with Long Covid, such as sensorineural hearing loss, esophageal problems, and neurological tinnitus.
The region of the world with the highest prevalence of the mutations, according to the HGI study, is East Asia, where 36 percent of the population are carriers.
WHAT ARE THE LONG COVID FOXP4 MUTATIONS?
Researchers identified four FOXP4 gene mutations associated with Long Covid. The most significant is called rs9367106. This mutation exists in only 1.6 percent of non-Finnish Europeans, but is found in 7.1 percent of Finnish people. It’s found in 19 percent of “admixed” (blended genetic) Americans, and in an astounding 36 percent of East Asians.
The other mutations are rs7741164, rs55889968, and rs9381074. This last one, rs9381074, is responsible for writing instructions for multiple tissues, including, perhaps significantly, immune cells, and more specifically, T cells.
Author’s note: The HGI report I read did not list the prevalence of these gene mutations in Native American or African populations, and I was unable to find it when I searched elsewhere. If I’d had it, I’d have mentioned them here.
WHAT ELSE CAN FOXP4 MUTATIONS DO?
FOXP4 writes instructions for many of the same parts of the body involved in Long Covid: the vasculature (blood vessels), lungs, stomach, testes, thyroid and cervix. The FOXP4 mutations now associated with Long Covid were already known to cause other diseases in these areas. It’s strongly associated, for example, with non-small cell lung carcinoma, and non-smoking lung cancer in Asian women. It’s considered “oncongenic,” meaning it encourages tumors to develop and then makes them grow faster.
The Long Covid gene mutations have also been previously linked to heritable health traits such as asthma and diabetes, and heritable mental health traits, including depression. Long Covid often occurs with pre-existing depression, but depression isn’t causing Long Covid. Rather, both depression and Long Covid seem to be linked to this causative genetic mutation. (Natalie Shure, are you listening?)
The author of this piece, who carries 3 of the 4 FOXP4 genetic mutations associated with Long Covid, has been sick since March 2020. Some girls have all the luck. Not this girl.
HOW CAN YOU FIND OUT IF YOU HAVE IT?
Testing for the FOXP4 gene mutations is not a standard medical practice at this time. For now, it will be up to us to provide our medical providers with the information we are learning, and, when possible, we will have to pay for our own genetic testing. I strongly recommend that if you choose to do this genetic testing, you do it with a trusted genetic counselor to help you deal with the difficult emotions it might raise.
WHAT CAN I DO ABOUT THE LONG COVID GENE?
Many gene mutations put carriers at greater risk of certain diseases or cancers. For instance, carriers of the BRCA1 or BRCA2 mutations are at greatly increased risk of deadly breast cancer. Consequently, many carriers of these genes opt for prophylactic mastectomies.
At this time, I’m unable to find any suggestions for people who carry the FOXP4 mutations. I hope research will start to be done in this area soon.
In the meantime, the only things we have in our control are lifestyle choices. Diet, stress, drug and alcohol use, tobacco use, can all make things worse for people, whether they carry the FOXP4 mutations or not.
So that’s what I’m doing with this information. I’m trying to control what I can, which, it seems, ain’t much.
I hope this piece was helpful. I’ll be continuing to follow developments about the FOXP4 mutations and Long Covid. Let’s spread the word to as many people as we can about this gene. Please consider a paid subscription to this newsletter. I’d like to make this work my full-time job, to help as many people as I can, and I can’t do it if I’m having to do it all for free. Thank you!