Health Shot: Long COVID's effect on the gut and serotonin levels

In a new study out of UPenn, researchers found that pieces of the COVID virus can remain in the gut and cause depleted serotonin levels

Before we dive into this week’s Health Shot, here’s what’s coming up in Inner Workings…

• insights from my personal experiences getting published in print and online lit mags (i.e. outside Substack)

• Lady’s Illness Library interviews with Amy of

  The Tonic
  , Ema Hegberg of
  Peace of the Whole
  , and others (these are quickly becoming such a rich source of community and inspiration for me)

• more Health Shots on the latest research in the world of autoimmunity, gut health, stress, and chronic illness

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Illustration by Stephanie Davidson for Mood Health

A new study published on Monday establishes a potential link between long COVID, gut function, and serotonin levels, offering a new explanation for neurological symptoms like brain fog and memory loss. The research suggests that pieces of the COVID virus can remain in the gut and cause inflammation, disrupting the serotonin pathway and reducing circulating serotonin levels in long COVID patients. Serotonin is one of the body’s most important neurotransmitters, influencing the function of the central nervous system and stabilizing mood. It is also involved in a broad set of bodily functions including sleeping, healing, and digesting, and blood clotting.

Before we dig into the details of this study, I want to put this in context: this notion that a virus can cause gut inflammation which can in turn inhibit serotonin production is novel in the context of long COVID, but it does not sound novel to my ear, or to anyone who follows what I’ll very scientifically call “mysterious illnesses and gut stuff.” I was shocked to learn all too recently, that 95% of our serotonin is produced in our intestines, which seems especially relevant given that one in ten Americans take anti-depressants, the majority of which target low serotonin levels. Women are more than twice as likely to take these medications. Personally, I have been on and off selective serotonin reuptake inhibitors (SSRIs) since I was twelve, and it seems like by age thirty I should have heard about this serotonin-gut connection.

And yet it does not seem to be a common area of knowledge among patients or doctors who are taking and prescribing serotonin-related medications. Research has long suggested that disruptions in the gut can affect serotonin levels—this is one of the major mechanisms people are referring to when they say the trendy phrase “gut-brain axis.” But the complete absence of this concept in standard medical practice is largely because there has not yet been a bloom of strong research on this pathway to underpin new therapeutic approaches.

So, I am hopeful that, in addition to laying a foundation for much-needed long COVID treatment options, this new work will also generate more research interest in the broader connection between the gut and the serotonin pathway. Anyone with gut dysbiosis, chronic fatigue, a variety of autoimmune diseases, depression, anxiety, and a host of other mental health conditions could be helped by new findings in this area.

Image from Serotonin reduction in post-acute sequelae of viral infection paper published in Cell

Serotonin reduction in post-acute sequelae of viral infection

» Study link

Study basics: In this study out of UPenn, researchers looked at blood samples from both lab animals and humans, and found that long COVID patients had notably depleted serotonin levels. They also examined stool samples, and found that many long COVID patients had fragments of the COVID virus in their stool months after the acute infection had resolved. This indicates that at least parts of the virus can remain in the digestive tract for long periods of time following the infection.

Major implications: The researchers hypothesize that the virus fragments in the gut set off an immune reaction that causes inflammation and inhibits the absorption of the amino acid tryptophan, one of the primary building blocks of serotonin. This would result in the lower circulating serotonin levels seen in the bloodwork.

And even though this study was focused on serotonin, the affects of tryptophan malabsorption can be wide-ranging, since it is a building block for other neurotransmitters as well.

Reactions: So far, this paper has been met with a highly positive response in the scientific community. Researchers have commented that it brings together a number of clues that have popped in the long COVID research to date, including lingering viral fragments (the “viral reservoir”), and the immune response, and elegantly combines these theories to come up with a potential explanation for previously mysterious cognitive and neurological symptoms.

As I said at the start, my hope here is that this will not only activate more research on effective long COVID treatments, but also on the gut-serotonin mechanisms at work in the many diseases that also include unexplained fatigue and cognitive symptoms, diseases which typically affect majority women.