Conquering Long COVID: Could Gut Health Hold the Key?

Summary

.
.

The COVID-19 pandemic has expanded our view on how viruses can impact us. People experience COVID-19 symptoms in different ways, and for an estimated 23 million Americans [1], recovery from the initial bout leads into a mysterious chronic condition known as long COVID. Symptoms of long COVID can be debilitating, from nerve pain, brain fog, and fatigue to chest pain, gut issues, depression, and more [2].

In this post, we'll explore how these seemingly unrelated symptoms may be connected to changes in our gut bacteria. We’ll discuss how our gut may impact the immune system and the cascading effects of imbalances (known as dysbiosis). Finally, we’ll share some advice on how to look after your gut health after having COVID-19.

What is long COVID?

The Centers for Disease Control and Prevention (CDC) defines ‘long COVID’ broadly as “signs, symptoms, and conditions that continue or develop after acute COVID-19 infection.” People call it by other names too, including Post-COVID Conditions, long-haul COVID, post-acute COVID-19, long-term effects of COVID, and chronic COVID.

Long COVID manifests as a spectrum of symptoms that can’t be explained by another diagnosis. They can last for months after COVID-19 illness and can affect a variety of systems throughout the body:

  • Autonomic: breathlessness, heart palpitations, nerve pain [3] 
  • Gastrointestinal: nausea, diarrhea, bloating, loss of appetite, acid reflux [4] 
  • Neurological: dizziness, fatigue, cognitive impairment including “brain fog” [5] 
  • Psychological: depression, anxiety, sleep disturbances, post-traumatic symptoms (PTS) [6]


Recognizing these mysterious symptoms as long COVID and finding effective treatment strategies is challenging. There is currently a significant gap in understanding and support for people affected. Now let’s explore what recent research shows about COVID-19 and its connection to the gut.

The gut connection to COVID-19 infection

Our gut is home to a vast community of microorganisms that play a vital role in keeping us healthy. The microbes in our gut not only keep our digestive tract running smoothly, they also help regulate our immune response [7], harvest energy and nutrients from our food [8], and even make the building blocks for neurotransmitters [9]—the chemical messengers between our brain and the rest of our body. 

Contracting COVID-19 can disrupt the balance in our gut, leading to the loss of beneficial bacteria, like Bifidobacterium and Faecalibacterium, and an increase in opportunistic microbial pathogens, like Streptococcus and Enterobacteriaceae. It is important to maintain a robust abundance of beneficial bacteria in your gut microbiome; these species are responsible for breaking down fiber and making short chain fatty acids (SCFA) that nourish intestinal cells and modulate our immune system [10]. 

COVID-19 illness is caused by the SARS-CoV-2 virus. When you are infected, the virus uses ACE2 receptors as doorways into your cells. ACE2 receptors are found throughout your body, but they exist in high abundance in your gut where they play a pivotal role in regulating blood pressure, fluid balance, and inflammation. When they are functioning properly, they help protect your cells from the virus by maintaining a balanced state [11]. This functioning can be impaired by gut dysbiosis. Dysbiosis weakens your gut’s defense against viruses, and allows for more severe infections. 

In fact, studies have found that COVID-19 patients with existing gut dysbiosis at the time of infection experience more severe symptoms and may be more likely to develop long COVID [12-14].

The Gut and your Immune System

One of the strongest links between the gut microbiome and how you experience COVID-19 is the interplay between your gut and your immune system. Your gut bacteria produce molecules that directly influence many aspects of your immune function, including:

  • Development of Immune Cells: Your gut microbial environment promotes the development of T cells, B cells, and natural killer cells.
  • Regulation of Inflammation: Certain gut bacteria produce molecules with anti-inflammatory properties that work to keep your gut tissue from being damaged during illness.
  • Barrier Function: A healthy gut microbiome is associated with a strong intestinal barrier, which keeps harmful bacteria from leaching out and circulating through your body.
  • Pathogen Defense: Certain beneficial bacteria can produce substances that inhibit or kill infectious microbes.


Additionally, the loss of beneficial bacteria may make more room for viruses to camp out, forming what is known as “viral reservoirs.” These persistent pools of viral microbes can lay low for a while and replicate, causing chronic health issues down the line [15]. 

Once you have been infected, the SARS-CoV-2 virus can spread to other parts of the body. The microbes in your gut communicate with the microbes in other body systems, mainly through your immune system. One of these two-way communication pathways is the “gut-lung axis.”  This is where gut inflammation and immune responses can impact lung health, potentially contributing to the respiratory symptoms associated with COVID-19. 

When COVID-19 becomes long COVID

If recovering from COVID-19 infections wasn’t enough of a hurdle, some people develop persistent long COVID symptoms such as fatigue, gut issues, or brain fog. These symptoms can develop immediately after the primary illness or re-appear months after recovery from COVID-19. 

In fact, it is estimated that over 30% of patients have at least one long COVID symptom within 3 months of infection and that number climbs to over 50% of patients reporting symptoms between 3-6 months post-infection [16]. 

Research suggests that these lasting problems may be related to gut dysbiosis, which can persist for more than 3-6 months after having COVID-19. Lasting dysbiosis begins to cause body-wide problems, primarily through heightened inflammation and/or the long-term loss of butyrate-producing beneficial bacteria [17]. Butyrate is one of the three key SCFAs in our bodies. It is responsible for making different molecules that send signals to regulate our digestive, respiratory and immune systems, and even support our mental well-being. In fact, a large portion of our neurotransmitters, the chemicals that control our mood and cognitive functioning, are made in the gut! 

One study that examined the gut microbiomes of long COVID patients one year after infection found a significant reduction in SCFA-producing bacteria [18]. Another study observed a correlation between lowered serotonin levels and long COVID symptoms [19]. Serotonin is a key neurotransmitter affecting mood, cognition, and numerous bodily functions. And guess what—its precursor, tryptophan, is made in the gut by SCFA-producing bacteria. 

These studies highlight how crucial good gut bacteria are for our health. Replenishing these friendly microbes after an illness such as COVID-19 is essential for keeping our bodies running smoothly. Tackling imbalances in the gut could lower your risk of developing long COVID and bolster overall health by supporting the interplay between your digestive, immune, and brain functions.

Restoring Gut Health after COVID-19 Illness 

While long COVID presents a daunting challenge, leaving many feeling overwhelmed, there are tangible steps you can take to support your recovery, particularly by focusing on restoring gut health.

1. Incorporate Probiotics: 

Probiotics, for example those containing Lactobacillus and Bifidobacterium species, have shown promise in alleviating gastrointestinal symptoms and reducing the severity of COVID-19. These beneficial bacteria may reinforce the gut barrier and influence the immune response by reducing inflammation [20]. Taking a microbiome test may help you identify which specific species and strains your gut may need.

2. Adopt a Microbiome-Friendly Diet: 

A diet rich in fruits, vegetables, whole grains, and fermentable fibers can promote the growth of beneficial gut bacteria, which in turn produce SCFAs such as butyrate. This may in turn help to calm down inflammatory responses and protect your gut lining [21].

3. Limit Processed Foods: 

Processed foods, saturated fats, and simple carbohydrates can exacerbate dysbiosis and inflammation. Opting for a balanced diet can support microbiome health and overall wellness [22].

4. Aim for a Healthy Lifestyle: 

Adequate sleep, regular exercise, and stress management are also important for maintaining gut health, particularly when trying to support the immune system [23], [24]. 

Chronic stress can lower your immune defenses by changing the balance between two key types of signals in the body, known as Type 1 and Type 2 cytokines. Think of it as adjusting the levels on a sound mixer to get the music just right. Too much or too little of either may cause inflammation and interfere with the function of protective immune cells, which may make it easier for you to get (or stay) sick [25].

Practically speaking, physical activity is a great stress reliever. Low-intensity exercise like yoga can speed up things moving through your gut, which means less time for harmful viruses and bacteria to stick around and cause trouble. This may help lower your chance of developing inflammatory-related gut issues [24]. 

Identify and correct gut imbalances to nurture your health

Recovering from COVID-19 can be easy for some but a long and difficult process for others. The connection between gut health and COVID-19 highlights the microbiome's role in our resiliency against infections. A healthy gut could potentially reduce COVID-19 symptoms and severity, and nurturing our gut after illness may help prevent long-term issues. Understanding the gut's influence on our health leads to better recovery strategies, including diet and probiotics.

Because our immune system is so connected with our gut, it may be helpful to know which beneficial species of bacteria are depleted in your gut, and which potentially unfriendly bacteria are in overabundance. Tiny Health is here to give you a comprehensive look into your gut microbiome. Our gut tests even flag bacterial species associated with multiple health conditions, including long COVID in our adult gut tests. And we provide you with personalized recommendations—from probiotics, foods, and lifestyle tips—and 1-on-1 coaching programs to help you recover after illness or improve your gut health proactively. 

As scientists continue to learn more about the connection between the gut and chronic conditions like long COVID, let's not forget to give our gut the TLC it deserves—it might just be the key to bouncing back stronger and healthier.

References

[1] U.S. Government Accountability Office, “Science & Tech Spotlight: Long COVID.” Accessed: Mar. 12, 2024. [Online]. Available: https://www.gao.gov/products/gao-22-105666

[2] A. M. Bogariu and D. L. Dumitrascu, “Digestive involvement in the Long-COVID syndrome,” Med Pharm Rep, vol. 95, no. 1, pp. 5–10, Jan. 2022, doi: 10.15386/mpr-2340.

[3] M. Dani et al., “Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies,” Clin. Med. , vol. 21, no. 1, pp. e63–e67, Jan. 2021, doi: 10.7861/clinmed.2020-0896.

[4] A. M. Bogariu and D. L. Dumitrascu, “Digestive involvement in the Long-COVID syndrome,” Med Pharm Rep, vol. 95, no. 1, pp. 5–10, Jan. 2022, doi: 10.15386/mpr-2340.

[5] Y. Mina et al., “Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection,” Neurol Neuroimmunol Neuroinflamm, vol. 10, no. 4, Jul. 2023, doi: 10.1212/NXI.0000000000200097.

[6] M. Marchi et al., “Psychiatric symptoms in Long-COVID patients: a systematic review,” Front. Psychiatry, vol. 14, p. 1138389, Jun. 2023, doi: 10.3389/fpsyt.2023.1138389.

[7] S. P. Wiertsema, J. van Bergenhenegouwen, J. Garssen, and L. M. J. Knippels, “The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies,” Nutrients, vol. 13, no. 3, Mar. 2021, doi: 10.3390/nu13030886.

[8] K. Oliphant and E. Allen-Vercoe, “Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health,” Microbiome, vol. 7, no. 1, p. 91, Jun. 2019, doi: 10.1186/s40168-019-0704-8.

[9] L. M. T. Dicks, “Gut Bacteria and Neurotransmitters,” Microorganisms, vol. 10, no. 9, Sep. 2022, doi: 10.3390/microorganisms10091838.

[10] T. Zuo et al., “Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization,” Gastroenterology, vol. 159, no. 3, pp. 944–955.e8, Sep. 2020, doi: 10.1053/j.gastro.2020.05.048. 

[11] Y. Guo, B. Wang, H. Gao, L. Gao, R. Hua, and J.-D. Xu, “ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology,” Front Mol Biosci, vol. 8, p. 708336, Sep. 2021, doi: 10.3389/fmolb.2021.708336. 

[12] Z. Sun et al., “Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients,” BMC Med., vol. 20, no. 1, p. 24, Jan. 2022, doi: 10.1186/s12916-021-02212-0.

[13] Q. Liu et al., “Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome,” Gut, vol. 71, no. 3, pp. 544–552, Mar. 2022, doi: 10.1136/gutjnl-2021-325989. 

[14] Q. Liu et al., “Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome,” Nat. Commun., vol. 13, no. 1, p. 6806, Nov. 2022, doi: 10.1038/s41467-022-34535-8. 

[15] M. Merad, C. A. Blish, F. Sallusto, and A. Iwasaki, “The immunology and immunopathology of COVID-19,” Science, vol. 375, no. 6585, pp. 1122–1127, Mar. 2022, doi: 10.1126/science.abm8108. 

[16] M. Taquet, Q. Dercon, S. Luciano, J. R. Geddes, M. Husain, and P. J. Harrison, “Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19,” PLoS Med., vol. 18, no. 9, p. e1003773, Sep. 2021, doi: 10.1371/journal.pmed.1003773. 

[17] T. Perlot and J. M. Penninger, “ACE2 - from the renin-angiotensin system to gut microbiota and malnutrition,” Microbes Infect., vol. 15, no. 13, pp. 866–873, Nov. 2013, doi: 10.1016/j.micinf.2013.08.003. 

[18] D. Zhang et al., “Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge,” J. Korean Med. Sci., vol. 38, no. 15, p. e120, Apr. 2023, doi: 10.3346/jkms.2023.38.e120. 

[19] A. C. Wong et al., “Serotonin reduction in post-acute sequelae of viral infection,” Cell, vol. 186, no. 22, pp. 4851–4867.e20, Oct. 2023, doi: 10.1016/j.cell.2023.09.013.

[20] M. Aziz, R. Fatima, and R. Assaly, “Elevated interleukin-6 and severe COVID-19: A meta-analysis,” Journal of medical virology, vol. 92, no. 11. pp. 2283–2285, Nov. 2020. doi: 10.1002/jmv.25948.

[21] E. M. Sajdel-Sulkowska, “Neuropsychiatric Ramifications of COVID-19: Short-Chain Fatty Acid Deficiency and Disturbance of Microbiota-Gut-Brain Axis Signaling,” Biomed Res. Int., vol. 2021, p. 7880448, Oct. 2021, doi: 10.1155/2021/7880448.

[22] I. Zabetakis, R. Lordan, C. Norton, and A. Tsoupras, “COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation,” Nutrients, vol. 12, no. 5, May 2020, doi: 10.3390/nu12051466.

[23] S. Garbarino, P. Lanteri, N. L. Bragazzi, N. Magnavita, and E. Scoditti, “Role of sleep deprivation in immune-related disease risk and outcomes,” Commun Biol, vol. 4, no. 1, p. 1304, Nov. 2021, doi: 10.1038/s42003-021-02825-4.

[24] V. Monda et al., “Exercise Modifies the Gut Microbiota with Positive Health Effects,” Oxid. Med. Cell. Longev., vol. 2017, p. 3831972, Mar. 2017, doi: 10.1155/2017/3831972.

[25] F. S. Dhabhar, “Effects of stress on immune function: the good, the bad, and the beautiful,” Immunol. Res., vol. 58, no. 2–3, pp. 193–210, May 2014, doi: 10.1007/s12026-014-8517-0.