No one knows how many people are suffering from long COVID. Health & Human Services (HHS) has estimated somewhere between 7.7 million and 23 million Americans have at one time experienced symptoms. Whatever the number, the long-term consequences of this viral infection can be devastating. Symptoms may include fatigue, cough, shortness of breath, palpitations, dizziness and brain fog. It is the brain fog, memory problems and cognitive complaints that can be especially challenging for many people. Such problems may be far more common than first suspected. Research suggests that cognitive decline could be, in part, caused by low serotonin levels resulting from a long COVID infection.
Long COVID & Brain Fog: A Worldwide Problem!
A study published in the New England Journal of Medicine (Feb. 29, 2024) suggests that a connection between long COVID & brain fog could be an international challenge. Researchers invited 800,000 British citizens to participate in an online survey, including cognitive assessment. Roughly 113,000 people completed all portions of the questionnaire.
Those who had experienced COVID infections but recovered quickly had a small drop in IQ, compared to people who did not catch COVID. In contrast, those reporting symptoms that lasted 12 weeks or more had a larger IQ deficit. These folks had a drop in IQ of six points. That may not seem like much, but it represents a substantial impact of long COVID.
Patients who reported brain fog performed less well on tests of memory, planning and reasoning. People who eventually recovered from long COVID also performed similarly to those who had brief COVID infections.
The authors report:
“Our results confirmed associations of cognitive deficits with mood swings and fatigue but also with a variety of other symptoms. Therefore, it is likely that multiple underlying factors contribute to cognitive deficits after Covid-19.”
“In this observational study, we found objectively measurable cognitive deficits that may persist for a year or more after Covid-19.”
An editorial that accompanies the research (New England Journal of Medicine, Feb. 29, 2024) admits that:
“The mechanisms of cognitive dysfunction after SARS-CoV-2 infection still need to be elucidated. Studies involving humans and mouse organoids showed that SARS-CoV-2 infection induces fusion of neurons, which compromises neuronal activity. Studies involving humans have shown prolonged neuroinflammatory responses, structural abnormalities, and accelerated aging in the brains of persons with mild-to-moderate SARS-CoV-2 infection.”
The authors call for better understanding of cognitive dysfunction after SARS-CoV-2 infection so that we can address the needs of affected people.
Low Serotonin Levels and Depression?
Most people never paid much attention to the neurotransmitter serotonin until Prozac (fluoxetine) was approved by the FDA. The drug was classified as an SSRI (selective serotonin reuptake inhibitor). In theory, this antidepressant was supposed to work by increasing serotonin levels in the brain.
However, last year we spoke with Dr. Joanna Moncrieff on our nationally syndicated public radio show. She is Professor of Critical and Social Psychiatry at University College London. She has authored many scientific papers and several books. In an article in Molecular Psychiatry, July 20, 2022,
Dr. Moncrieff and her colleagues conclude:
“Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers.”
Although Prozac and similar antidepressants may not work by “fixing” low serotonin levels, it is possible that viral infections may have long lasting negative consequences on this neurotransmitter.
Could Low Serotonin Levels Lead to Brain Fog?
Researchers at the University of Pennsylvania offer a novel theory about brain fog and long COVID. Their article was published in the journal Cell (Oct. 16, 2023). It was titled:
“Serotonin reduction in post-acute sequelae of viral infection”
Post-acute sequelae of COVID-19 (PASC) is a fancy way of saying long COVID.
The investigators found persistent viral remnants in the digestive tracts of patients. These appear to contribute to inflammation and a reduction in serotonin levels throughout the body.
Serotonin is crucial for brain function. But 90 percent of this neurotransmitter is actually made within the digestive tract.
Inflammation in response to the SARS-CoV-2 viral debris apparently interferes with the production of serotonin. This may, in part, account for some of the neurological symptoms of long COVID, including brain fog and cognitive dysfunction.
Viral Infection and Low Serotonin:
The study in the journal Cell reported that it’s not just COVID-19 that causes serotonin depletion:
“We first explored whether serotonin depletion was unique to COVID-19 or whether other acute viral infections led to a similar decrease. To this end, we measured serotonin levels in the plasma of 33 individuals with non-SARS-CoV-2 systemic viral infections and compared them to 20 healthy controls. As in acute COVID-19, serotonin levels were strongly decreased by other viral infections, suggesting that this might be a more general characteristic of systemic viral infection.”
Keep in mind that chronic fatigue syndrome (now called myalgic encephalomyelitis/chronic fatigue syndrome or ME/CFS) has been around long before COVID-19. Because of this, we think the U of Penn researchers have uncovered something quite important.
They conclude:
“The connection between serotonin reduction and vagus nerve dysfunction may thus be relevant beyond Long COVID. The fact that low serotonin levels are also found in non-viral conditions characterized by elevated interferon levels, such as systemic lupus erythematosus or multiple sclerosis, suggests that the pathway described in this study may even apply beyond viral infections.”
Final Words:
No one can say with certainty that low serotonin levels account for brain fog, memory problems and cognitive complaints. Nevertheless, this research is extremely provocative.
We have long believed that the vagus nerve has been underestimated by neuroscientists when it comes to things like depression and brain health. Should you be interested in this area of research, you may find our radio interview, “Harnessing the Power of the Vagus Nerve,” quite relevant. Here is a link.
Implications for treating long COVID?
An article and interview on NPR titled “Long COVID brain fog may originate in a surprising place, say scientists,” offers some intriguing ideas for going forward. A senior author of the Penn study is Christoph Thaiss.
His interview with NPR provides this insight:
‘”We can make the animals remember perfectly again by just reactivating their vagus nerve or by restoring their serotonin signaling,’ says Thaiss, referring to a cognitive behavioral test they performed on their mouse models of long COVID.
“Whether the exact same thing is true in individuals with long COVID is something we don’t know.”
Another senior author on the paper is Maayan Levy. She adds:
“Levy says they found this reduction in serotonin impairs communication between the vagus nerve and the brain, which then reduces some activity in a region of the brain known as the hippocampus.
“What’s promising, though, is that the cognitive symptoms the Penn researchers documented in mice could be reversed.
The scientists are less sure that they can do this for humans with long COVID:
“‘To make any recommendations for patients, we need to perform a large clinical trial that is well-controlled,’ she [Levy] says, ‘The obvious next step would be for us to to try an intervention that will increase serotonin levels or stimulate the vagus nerve in other ways or [to] supplement tryptophan.'”
Please share your own experience with long COVID in the comment section below.
