Long COVID & Exercise: Could Movement Be Our Medicine?

Will we ever move past COVID-19?

Funny enough, some of us already have! Others of us don’t quite have that option!

It’s amazing how little we know about the coronavirus, this late in the game! Of course, it is a novel virus, but it’s amazing that it’s still held onto its novelty even 5 years later!

What is Long COVID?

Of course we’re all familiar with COVID-19 & its huge variety of symptoms; from the cough to the sore throat, to a fever and chills, aches & pains, and then, maybe the most frightening of them all, the dreaded brain fog.

It wasn’t, and still isn’t, an uncommon occurrence for one to be infected with the virus, recover from their illness, and yet, to still not feel quite right…

“At least 65 million individuals around the world have Long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases. The incidence is estimated at 10–30% of non-hospitalized cases, 50–70% of hospitalized cases and 10–12% of vaccinated cases [1].”

Long COVID is a debilitating, multi-system condition that develops following a SARS-CoV-2 infection; characterized by one or more of the many COVID-19 symptoms lingering for months to even years! It can attack any of multiple organs & present with any combination of impairments; being shown to facilitate cardiovascular, thrombotic and cerebrovascular diseases, type 2 diabetes, chronic fatigue syndrome, prolonged cognitive slowing, and disruptions of your autonomic nervous system [1,2]! Unfortunately, many of the resulting impairments from Long COVID are actually a lifetime sentence!

Figure 1 from the Davis, McCorkell, Vogel, & Topof article

Highlighting the impacts of Long COVID on the various organ systems & the potential pathologies it may facilitate.

Theories on Long COVID

Most concerning about Long COVID is that we still don’t really understand why it happens, let alone why it can vary so wildly from host to host!

Hopefully, once we’ve identified the root cause of the disorder, we can bring forth some worthwhile treatments. There are multiple working theories as to what may be the underlying mechanism for this strange pathology; all extremely plausible, but uniquely different!

Proal & VanElzakker outlined 6 of the most prevalent hypotheses in their recent paper. In their findings, the two highlighted:

1) The development of reservoirs of SARS-CoV-2 in the tissues [3,4].

Multiple studies are showing that some patients, over prolonged periods of time post-acute COVID, are still unable to successfully clear SARS-CoV-2 from their system! SARS-CoV-2 RNA has been found lingering in a variety of tissues & organs many months after infection!

2) SARS-CoV-2 infection resulting in the dysregulation of the immune system [3,5].

Following acute COVID-19, it has been shown that the host’s immune system is weakened & “dysregulated”, making them susceptible to additional, equally harmful viruses!

3) SARS-CoV-2 infection resulting in an excessive & abnormal auto-immune response [3,6].

Post-COVID, it has been observed that patients present with a large variety of rare and excessive “autoantibody” reactions. The antibodies produced have been shown to vary wildly & to be extremely patient-specific, potentially explaining how variable Long-COVID can be in its presentation.

4) SARS-CoV-2 adversely affecting the human microbiome & virome [3,7].

Studies that have involved introducing the gut microbiota of Long-COVID patients to healthy animal models have consistently shown the production of those Long-COVID type symptoms in their respective models, including lung inflammation & brain fog!

5) SARS-CoV-2 leading to dysfunctional signalling of the brainstem and vagus nerve [3,8].

Many Long COVID patients present with symptoms – a disrupted autonomic nervous system, diffuse pain, trouble sleeping & concentrating – that meet the diagnostic criteria for Chronic Fatigue Syndrome! The brainstem plays a huge role in the sickness response as well as in control of the autonomic nervous system; thus it’s been suggested that dysfunctional brainstem signaling may be the key driver for Long COVID symptoms, similarly to the role it plays in Chronic Fatigue Syndrome patients!

A majority of the cell bodies of the vagus nerve are also found in the brainstem. The vagus nerve is a huge, parasympathetic nerve that plays a role in a variety of bodily functions & responses. This connection could also speak to Long COVID’s varied presentation!

6) SARS-CoV-2 produces an eruption of microvascular blood clots as well as endothelial dysfunction [3,9-11].

SARS-CoV-2 leads to the production & secretion of proteins that facilitate blood clotting cascades that form a multitude of “microclots”, as well as inflammation & damage to the cells that line your blood vessels! Of course, all of our organs are reliant on appropriate blood flow to continue functioning property; it isn’t hard to envision extensive clotting & inflammation, as well as reduced blood flow producing any of the vast pool of Long COVID symptoms!

Figure 3 from the Davis, McCorkell, Vogel, & Topof article, highlighting 5 of the 6 hypotheses

There’s sufficient evidence to greatly support each of these 6 hypotheses. For that reason, most would consider their to be some significant overlap. When it comes to Long COVID, it’s not just one thing that’s gone wrong, it’s a bunch!

Long COVID & Exercise

We’ve come so far and yet still have so few answers; unfortunately, with so many potential underlying mechanisms, it doesn’t seem like we’ll be getting a worthwhile treatment any time soon!

Constant fatigue, brain fog, and aches & pains could easily drive someone to a sedentary life full of anxiety & depression; actually, we’re already seeing plenty of our neighbors taking on that exact lifestyle!

While it may seem like the smart play to be constantly resting, “preserving” your energy, that may actually be doing more harm than good! In fact, it could be our increasingly sedentary lifestyles that are predisposing us to Long COVID!

There is a growing body of literature suggesting that physical rehabilitation may be useful as a treatment for Long COVID.

A routine consisting of progressive aerobic exercise training to increase activity tolerance, as well as breathing exercises to strengthen respiratory muscles & increase functional capacity has consistently been shown to be beneficial in Long COVID patients [12]!

There are also studies that put Long COVID patients through tailor-made exercise programs, consisting of progressive aerobic training & light to moderate resistance training, that show that those patients that undergo exercise training post-COVID report better quality of life, strength, and symptom outcomes compared to their peers [14]!

While there are concerns for Long COVID patients with the Chronic Fatigue Syndrome-type presentation; the literature generally suggests that appropriately timed & progressed exercise training is more beneficial than pacing or any passive treatment & equally as beneficial as cognitive behavioral therapy [15]!

When we consider the great multitude of benefits simply being active & living a healthy lifestyle can present to us, regardless of impairment, it seems like common sense that movement would be our medicine here!

Long COVID can be a debilitating & severely limiting pathology, but choosing to wait passively for a miracle treatment will definitely set you back a great deal!

Exercise has been shown time and time again to help improve your cardiorespiratory fitness, build muscle strength, improve your immunity, prevent & limit chronic diseases, and maximize your mental health [16]!

How long can you wait to take your health into your own hands? Life still has to go on, doesn’t it? The best way to get back to normal post-pandemic is to get up & get active!

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Works Cited & Further Reading

1. Davis, H. E., McCorkell, L., Vogel, J. M., & Topol, E. J. (2023). Long COVID: major findings, mechanisms and recommendations. Nature reviews. Microbiology, 21(3), 133–146. https://doi.org/10.1038/s41579-022-00846-2

2. Zhao, S., Martin, E. M., Reuken, P. A., Scholcz, A., Ganse-Dumrath, A., Srowig, A., Utech, I., Kozik, V., Radscheidt, M., Brodoehl, S., Stallmach, A., Schwab, M., Fraser, E., Finke, K., & Husain, M. (2024). Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study. EClinicalMedicine, 68, 102434. https://doi.org/10.1016/j.eclinm.2024.102434

3. Proal, A. D., & VanElzakker, M. B. (2021). Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Frontiers in microbiology, 12, 698169. https://doi.org/10.3389/fmicb.2021.698169

4. Swank, Z., Senussi, Y., Manickas-Hill, Z., Yu, X. G., Li, J. Z., Alter, G., & Walt, D. R. (2023). Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 76(3), e487–e490. https://doi.org/10.1093/cid/ciac722

5. Phetsouphanh, C., Darley, D. R., Wilson, D. B., Howe, A., Munier, C. M. L., Patel, S. K., Juno, J. A., Burrell, L. M., Kent, S. J., Dore, G. J., Kelleher, A. D., & Matthews, G. V. (2022). Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nature immunology, 23(2), 210–216. https://doi.org/10.1038/s41590-021-01113-x

6. Wang, E. Y., Mao, T., Klein, J., Dai, Y., Huck, J. D., Jaycox, J. R., Liu, F., Zhou, T., Israelow, B., Wong, P., Coppi, A., Lucas, C., Silva, J., Oh, J. E., Song, E., Perotti, E. S., Zheng, N. S., Fischer, S., Campbell, M., Fournier, J. B., … Ring, A. M. (2021). Diverse functional autoantibodies in patients with COVID-19. Nature, 595(7866), 283–288. https://doi.org/10.1038/s41586-021-03631-y

7. Mendes de Almeida, V., Engel, D. F., Ricci, M. F., Cruz, C. S., Lopes, Í. S., Alves, D. A., d' Auriol, M., Magalhães, J., Machado, E. C., Rocha, V. M., Carvalho, T. G., Lacerda, L. S. B., Pimenta, J. C., Aganetti, M., Zuccoli, G. S., Smith, B. J., Carregari, V. C., da Silva Rosa, E., Galvão, I., Dantas Cassali, G., … Vieira, A. T. (2023). Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms. Gut microbes, 15(2), 2249146. https://doi.org/10.1080/19490976.2023.2249146

8. Spudich, S., & Nath, A. (2022). Nervous system consequences of COVID-19. Science (New York, N.Y.), 375(6578), 267–269. https://doi.org/10.1126/science.abm2052

9. Pretorius, E., Venter, C., Laubscher, G. J., Kotze, M. J., Oladejo, S. O., Watson, L. R., Rajaratnam, K., Watson, B. W., & Kell, D. B. (2022). Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovascular diabetology, 21(1), 148. https://doi.org/10.1186/s12933-022-01579-5

10. Arthur, J. M., Forrest, J. C., Boehme, K. W., Kennedy, J. L., Owens, S., Herzog, C., Liu, J., & Harville, T. O. (2021). Development of ACE2 autoantibodies after SARS-CoV-2 infection. PloS one, 16(9), e0257016. https://doi.org/10.1371/journal.pone.0257016

11. Cervia-Hasler, C., Brüningk, S. C., Hoch, T., Fan, B., Muzio, G., Thompson, R. C., Ceglarek, L., Meledin, R., Westermann, P., Emmenegger, M., Taeschler, P., Zurbuchen, Y., Pons, M., Menges, D., Ballouz, T., Cervia-Hasler, S., Adamo, S., Merad, M., Charney, A. W., Puhan, M., … Boyman, O. (2024). Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science (New York, N.Y.), 383(6680), eadg7942. https://doi.org/10.1126/science.adg7942

12. Najafi, M. B., & Javanmard, S. H. (2023). Post-COVID-19 Syndrome Mechanisms, Prevention and Management. International journal of preventive medicine, 14, 59. https://doi.org/10.4103/ijpvm.ijpvm_508_21

13. Chuang, H. J., Lin, C. W., Hsiao, M. Y., Wang, T. G., & Liang, H. W. (2024). Long COVID and rehabilitation. Journal of the Formosan Medical Association = Taiwan yi zhi, 123 Suppl 1, S61–S69. https://doi.org/10.1016/j.jfma.2023.03.022

14. Jimeno-Almazán, A., Franco-López, F., Buendía-Romero, Á., Martínez-Cava, A., Sánchez-Agar, J. A., Sánchez-Alcaraz Martínez, B. J., Courel-Ibáñez, J., & Pallarés, J. G. (2022). Rehabilitation for post-COVID-19 condition through a supervised exercise intervention: A randomized controlled trial. Scandinavian journal of medicine & science in sports, 32(12), 1791–1801. https://doi.org/10.1111/sms.14240

15. Larun, L., Brurberg, K. G., Odgaard-Jensen, J., & Price, J. R. (2017). Exercise therapy for chronic fatigue syndrome. The Cochrane database of systematic reviews, 4(4), CD003200. https://doi.org/10.1002/14651858.CD003200.pub7

16. Ruegsegger, G. N., & Booth, F. W. (2018). Health Benefits of Exercise. Cold Spring Harbor perspectives in medicine, 8(7), a029694. https://doi.org/10.1101/cshperspect.a029694