Long COVID, Inflammation, and the Gut-Brain Axis


More than 92 million Americans have reported cases of COVID-19 since the pandemic’s start, and recent stats released by the Centers for Disease Control and Prevention (CDC) suggest that approximately 35% of those who have had the virus have experienced long COVID (symptoms that persisted for 3 months or longer). The organization also stated that 1 in 5 adults aged 18 or older have experienced a health condition that might be related to a previous COVID illness.

This is not surprising, as inflammation is associated with long COVID, and it impacts the health of the brain and gut (and therefore the whole body). We already know that persistent inflammation leads to serious physical consequences, from cancer to heart disease, and that it may also play a role in neurological and psychiatric illnesses, such as bipolar disorder, obsessive-compulsive disorder (OCD), schizophrenia, Alzheimer’s disease, and Parkinson’s disease—as well as other common mental health issues such as depression and anxiety.

Let’s explore the links between inflammation, long COVID, and the gut-brain axis to determine what’s behind these associations—and how healthier lifestyle and dietary choices can help reduce flare-ups of inflammation in the body to maintain better health over the long haul, even if you’re a COVID long-hauler.

Take note if you’re experiencing issues like anxiety, depression, and brain fog—or if you find yourself coping with these disturbances through drug or alcohol abuse—after recovering from a COVID-19 infection. Click To Tweet


Inflammation has been linked to long COVID by the National Institutes of Health, which points to a 2022 study on hamsters that showed extensive inflammation long after the virus left the body—specifically, in the olfactory epithelium (the lining inside the nose) and the olfactory bulb, a part of the brain involved in processing smell as well as in emotion and learning. Inflammation in these areas persisted long after the infection was cleared, and it was present alongside behavioral changes in the hamsters that pointed toward mood disorders like depression as well as anxiety.

“This suggests that the inflammation seen in the hamsters may explain the mechanism responsible for symptoms of long COVID in people,” the study reported, adding that further research is needed to fully understand the link between brain inflammation, brain activity, and behavioral changes—and, ideally, to help create future treatments to address this phenomenon.

Another study published in 2022 in Nature Immunology showed a chronic inflammatory response among patients who had experienced a mild to moderate case of COVID. The results stated that these findings “suggest that SARS-CoV-2 infection exerts unique prolonged residual effects on the innate and adaptive immune systems and that this may be driving the symptomology known as long COVID.”


Inflammation, with its connotation of fire, is not necessarily a negative force in the body—it’s actually a first responder sent by the immune system to attack and trap harmful microbes or other invaders that have entered, and to help heal injured tissue. When the problem has been controlled, the inflammation usually subsides as the immune system returns to its neutral state. Problems arise when inflammation becomes chronic (lasting longer than needed), and this once-helpful response instead creates ongoing damage to the organs and tissues of the body, including the brain.

The human gut, meanwhile, communicates with the brain via a complex system of neurons—a back-and-forth exchange known as the gut-brain axis, which includes the immune pathway. The human gastrointestinal tract houses trillions of micro-organisms that plays a role in inflammatory disease and immune response, according to a growing body of scientific evidence shows. These organisms fend off pathogens that, if they are left to multiply, lead to infection and disease. The gut needs about 85% beneficial bacteria to remain functioning optimally, so when the unhealthy portion rises above 15%, health problems ensue.

In other words, gut health is inextricably linked to overall health. A leaky gut, for example, can lead to chronic inflammation and other issues, from seasonal allergies and autoimmune diseases to Alzheimer’s. When chronic inflammation becomes a concern, its typical markers include low omega-3 fatty acid levels, gum disease, high levels of C-reactive protein and homocysteine (an amino acid), and infections. A healthy gut, however, helps sustain a healthier body—including optimal mental health.


We already know that COVID-19 creates brain fog, which is also referred to as “COVID Brain.” A large brain imaging study on COVID-19 patients noted that several brain-related changes could explain this phenomenon: a loss of gray matter thickness and tissue damage in areas linked to the olfactory system (i.e., sense of smell), reduction in total brain volume, and atrophy in a part of the cerebellum that is linked with cognition.

Another report, detailing research from the American Academy of Neurology’s annual meeting, explained that those with even mild cases of COVID-19 who experienced longer-term cognitive issues had higher levels of immune activation and immunovascular markers in their cerebrospinal fluid (CSF) nearly a year after infection. Study lead Dr. Joanna Hellmuth of the University of California, San Francisco, shared that these findings imply that this continuing vascular injury and repair in the brain may lead to an overactive immune response and inflammation, which then create the cognitive changes and brain fog associated with long COVID.

Meanwhile, researchers are finding that inflammation is also associated with mental health issues like depression. A 2022 study in BMJ found that people who have had COVID—from mild to severe cases—are at significantly higher risk of experiencing mental health problems, including anxiety, depression, suicidal ideation, sleep disturbances, and cognitive decline.

One study that examined the interaction between inflammation and mood disorders found that inflammatory cytokines had direct effects on levels of mood neurotransmitters such as dopamine and serotonin, as well as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (common in major depressive disorder), central nervous system function, impaired neuroplasticity, and structural and functional brain changes.

Take note if you’re experiencing issues like anxiety, depression, and brain fog—or if you find yourself coping with these disturbances through drug or alcohol abuse—after recovering from a COVID-19 infection. Remain aware of any changes in your emotional health and, if necessary, obtain further testing. Brain SPECT imaging, for example, measures blood flow and activity in the brain and can help determine if inflammation or another factor is causing the concern. It’s better to catch underlying issues early so they don’t worsen over time.


Whether or not you’re a COVID long-hauler, you can keep your gut in its healthiest state and hold chronic inflammation at bay with some simple steps:

  1. Brush your teeth after meals and floss daily to prevent gum disease (which is also linked to depression).
  2. Take a daily multivitamin with extra vitamin D, and, if homocysteine levels are high, a supplement with vitamins B6, B12, and folate.
  3. Boost your omega-3 levels with an EPA/DHA supplement and by eating more walnuts, salmon, sardines, beef, and avocado.
  4. Treat any possible sources of inflammation, such as infections, as soon as possible.
  5. Eat probiotic-rich fermented foods, such as kimchi, sauerkraut, kefir, miso soup, pickles, and kombucha tea.
  6. Increase intake of high-fiber foods—try artichokes, beans, cabbage, chia seeds, root veggies like sweet potatoes, jicama, and squashes.
  7. Consume prebiotic foods, which feed healthy gut microflora: garlic, leeks, onions, asparagus, bananas, and barley.
  8. Limit trans fats, omega-6 rich foods (found in corn, soy, and processed foods), sugar, gluten, and processed meats.
  9. Eliminate alcohol consumption, artificial sweeteners, and fried foods.
  10. Reduce chronic stress, which can create inflammation in the body, through exercise, yoga, diaphragmatic breathing, hypnosis, and/or meditation.
  11. Beware of additional contributing factors: exposure to environmental toxins, sleeplessness, childhood trauma, obesity, prediabetes and diabetes, excess strenuous exercise, and smoking.

Anxiety, depression, brain fog, and other mental health issues associated with COVID can’t wait. At Amen Clinics, we’re here for you. We offer in-clinic brain scanning and appointments, as well as mental telehealth, clinical evaluations, and therapy for adults, teens, children, and couples. Find out more by speaking to a specialist today at 888-288-9834 or visit our contact page here.

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