What Can Chronic Lyme Teach Us About Chronic COVID?

By Daniel A. Kinderlehrer MD


About the Author

Daniel Kinderlehrer, MD, is a nationally recognized physician with expertise in the fields of nutrition, allergy, environmental medicine, Lyme disease, and the healing of mind-body-spirit as a unified whole. He recently released a new book Recovery from Lyme Disease, The Integrative Medicine Guide to Diagnosing and Treating Tick-Borne Illness. The book discusses his integrative approach and offers the most up-to-date and comprehensive plan available for treating and beating this disease

One-third of patients who were sick with Covid-19 have come down with chronic symptoms, now known as Long Covid a.k.a Long-Hauler Syndrome a.k.a Post-Covid Syndrome. (1) For the most part, these are people who had mild SARS-CoV-2 infections. And although vaccinations mostly protect patients from serious illness and death, recent data suggests that breakthrough cases of vaccinated people who catch the virus are at the same risk of developing Long Covid as the unvaccinated. (2) As yet, we don’t have data on the Omicron variant and Long Covid.

Distressingly familiar symptoms

The symptoms of Long Covid are distressingly familiar to patients who suffer from persistent illness with Lyme disease: severe fatigue, muscle aches, and joint pains, impaired cognition (“brain fog”), insomnia, headaches, sleep disorders, cough, and shortness of breath, palpitations, and lightheadedness. (3,4) Many patients have also reported mood issues with anxiety, depression, and even psychosis.(3-5)

Like the condition we call chronic Lyme, Long Covid can be totally disabling, with people exhausted or short of breath after walking across the room. Sometimes these symptoms last a few months, but some folks are still ill for over a year without respite. There are now reported suicides among those who were suffering from Long Covid. (6)

Those of us who are treating patients with chronic tick-borne infections witness these same symptoms every day in our patients. It is likely that these disorders have similar pathogenesis.

It’s a software problem

In patients with chronic Lyme, the issue is not microbes invading tissue, the way we imagine a strep throat or a wound infection, essentially disrupting cellular hardware.

Instead, these patients have a software or regulatory problem. Chaos in the immune system leads to immune suppression, autoimmunity, and systemic inflammation; (7,8) hormonal imbalances lead to fatigue and decreased resistance to infection; (9) disorders of the nervous system results in impaired cognition, sleep disorders, and neuropsychiatric symptoms. (10)

No matter the cause, chronic inflammation has severe consequences. It often results in dysautonomia: disorder in the autonomic nervous system (ANS). In a healthy individual, the ANS employs the sympathetic arm (mostly stimulatory), with the parasympathetic (calming), to keep us well-balanced, in homeostasis. 

But when the ANS is inflamed and out of balance, the result is fluctuations in pulse and blood pressure—with palpitations, lightheadedness, and passing out. Dysautonomia can also trigger a myriad of other symptoms including shortness of breath, heat and cold intolerance, sweats, and anxiety. (11) 

Mast Cell Activation Syndrome

Further downstream effects of systemic inflammation manifest as sensitivity syndromes, particularly to foods and mold. Mast cells are primitive white blood cells that evolved to protect our mucous membranes from invasion. When they become trigger happy, they discharge histamine and a squadron of other inflammatory mediators called cytokines.

This is called Mast Cell Activation Syndrome. MCAS causes an array of symptoms including hives, flushing, itching, swelling, headaches, brain fog, and pain syndromes. The cytokines released by MCAS stimulate the vagus nerve (the tenth cranial nerve), which can worsen symptoms of dysautonomia, impair cognition, and trigger neuropsychiatric symptoms, gastrointestinal syndromes, and breathing problems. (12)

And compounding the felony, the vagus nerve can further trigger mast cells to degranulate and release their inflammatory messengers. (13) It’s a self-perpetuating cycle that leads to even more inflammation, disabling symptoms, and disability.

Patients with chronic Lyme frequently have endocrine issues. The most common is dysregulation of the adrenal glands and abnormal thyroid metabolism. Not only will these contribute to fatigue, but also to immune suppression. (14,15)

Meanwhile, immune suppression can result in activation of previously dormant viral infections like Epstein-Barr virus, which in turn contributes to fatigue, pain, and inflammation. (16)

In addition, chronic inflammation and infection can result in hyperviscosity issues, in which “thick blood” slows circulation, reducing delivery of oxygen, nutrients, and medications to cells. (17)

Finally, chronic inflammation results in oxidative stress, in which highly reactive molecules called free radicals interfere with normal metabolisms, like mitochondrial function. (18) Mitochondria are the energy-producing organelles in each of our cells, and mitochondrial dysfunction can result in debilitating fatigue.

These same issues are present in the unfortunate thousands of people suffering from Long Covid. 

Similarities between chronic Lyme and Long Covid

In its acute stages, SARS-CoV-2 can invade tissues and cause life-threatening organ damage. But in its chronic stage, the pathophysiology appears similar to chronic Lyme—targeting software, not hardware. The result is pandemonium in our regulatory systems, with immune, endocrine, and nervous system dysfunction, and all the downstream issues associated with chronic inflammation.

As with patients with chronic Lyme, those with Long Covid suffer from autoimmune inflammation. Antibodies to SARS-CoV-2 cross-react with multiple tissues including the gut, lung, heart, and brain. (19) There are now reports of SARS-CoV-2 infection resulting in PANS, Pediatric Acute-onset Neuropsychiatric Syndrome—autoimmune inflammation of the brain resulting in severe mood and behavioral symptoms in children and adolescents. (20)

According to most clinical descriptions of Long Covid patients, the majority suffer from severe dysautonomia, with wild fluctuations in pulse and blood pressure. (21) In addition, many patients have evidence of adrenal insufficiency and thyroid dysregulation, with elevations in thyroid antibodies and increased reverse T3. (22-24)

And, consistent with their excess inflammation and hyperreactive state, many Long Covid patients have developed food sensitivities and suffer from excessive mast cell activation. (25) And no surprise, SARS-CoV-2 infection creates oxidative stress that impairs mitochondrial function. (26)

SARS-CoV-2 can also result in hyperviscosity syndromes, sometimes severe enough to require anticoagulation. (27)

Reactivation of Latent Viruses

As with chronic Lyme, immune dysregulation promoted by SARS-CoV-2 infection can result in the reactivation of latent viruses. Researchers in the United States and Turkey found that two-thirds of patients with Long Covid had a reactivated Epstein-Barr virus infection compared to only 10% of controls. (28)

Here is something to think about: How many patients with Long Covid actually have Chronic Lyme that was activated by the viral insult? This has been reported to me by my colleagues. The two microbes most associated with this activation phenomenon are Bartonella and Mycoplasma, both capable of causing serious autoimmune problems. (29,30) And some folks suffering from chronic Lyme have relapsed after getting Covid.

In other words, it’s complicated. Inflammation is widespread and there are imbalances throughout the body. There is no single intervention that can heal those who suffer from Long Covid. 

Time for a good medical detective

Long Covid patients require careful medical detective work that uncovers the underlying imbalances. Interventions include decreasing inflammation; normalizing endocrine function; stabilizing the autonomic nervous system; supporting mitochondrial function; uncovering sensitivity syndromes; addressing mast cell activation syndrome and vagal nerve dysfunction; and treating reactivated infections. 

One more thought. It is now clear that some patients with Long Covid improve when they are vaccinated. (31) This suggests that these folks may still have active infection with the coronavirus. We know that SARS-CoV-2 has the capacity to disable and evade the immune response, (32) and some patients do not successfully clear the virus over long periods of time. (33,34) 

As we learn more, it may be appropriate to treat persistent SARS-CoV-2 infection in patients with Long Covid with anti-viral drugs that are now becoming available. While the Infectious Disease Society of America maintains otherwise, there is a wealth of data and clinical experience that antibiotics are effective in treating patients with chronic Lyme. (33)

The good news is that we have been largely successful in treating our patients with chronic Lyme. Ninety percent of my patients get 80 to100% better, even after being ill for years. It’s a careful process that involves detective work, trial, and error, curiosity, and determination. Let’s hope the same is true for those with Long Covid.


    1. Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(2):e210830. 
    2. https://www.medrxiv.org/content/10.1101/2021.10.26.21265508v1 (Accessed November 9, 2021)
    3. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351#:~:text=Long%2Dterm%20effects%20COVID,within%20a%20few%20weeks. (Accessed November 30, 2021)
    4. Taquet M, Dercon Q, Luciano S, Geddes JR, Husain M, Harrison PJ. Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Med. 2021;18(9):e1003773. doi:10.1371/journal.pmed.1003773
    5. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study [published correction appears in Lancet Psychiatry. 2020 Jul 14;:]. Lancet Psychiatry. 2020;7(10):875-882. doi:10.1016/S2215-0366(20)30287-X
    6. Sher L. Post-COVID syndrome and suicide risk. QJM. 2021;114(2):95-98. doi:10.1093/qjmed/hcab007
    7. Singh SK, Girschick HJ. Lyme borreliosis: from infection to autoimmunity. Clin Microbiol Infect. 2004;10(7):598-614. doi:10.1111/j.1469-0691.2004.00895.x
    8. Lochhead RB, Strle K, Arvikar SL, Weis JJ, Steere AC. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatol. 2021;17(8):449-461. doi:10.1038/s41584-021-00648-5
    9. Silverman MN, Heim CM, Nater UM, Marques AH, Sternberg EM. Neuroendocrine and immune contributors to fatigue. PM R. 2010;2(5):338-346. doi:10.1016/j.pmrj.2010.04.008
    10. Pegah Touradji, John N Aucott, Ting Yang, Alison W Rebman, Kathleen T Bechtold, Cognitive Decline in Post-treatment Lyme Disease Syndrome, Arch Clin Neuropsychol. 2019;34(4):455–465, https://doi.org/10.1093/arclin/acy051
    11. https://www.ninds.nih.gov/Disorders/All-Disorders/Dysautonomia-Information-Page (Accessed November 30, 2021)
    12. Aken C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017;140:349-55.
    13. Stead RH, Colley EC, Wang B, et al. Vagal influences over mast cells. Auton Neurosci. 2006;125(1-2):53-61. doi:10.1016/j.autneu.2006.01.002
    14. Bancos I, Hazeldine J, Chortis V, et al. Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality. Eur J Endocrinol. 2017;176(4):471-480. doi:10.1530/EJE-16-0969
    15. Schoenfeld PS, Myers JW, Myers L, LaRocque JC. Suppression of cell-mediated immunity in hypothyroidism. South Med J. 1995;88(3):347–349. 
    16. Koester TM, Meece JK, Fritsche TR, Frost HM. Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases. Clin Med Res. 2018;16(3-4):66-68.
    17. Sloop GD, De Mast Q, Pop G, Weidman JJ, St Cyr JA. The Role of Blood Viscosity in Infectious Diseases. Cureus. 2020;12(2):e7090. 
    18. Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015;5:66-70. 
    19. Taefehshokr N, Taefehshokr S, Hemmat N, Heit, B. Covid-19: perspectives on innate immune evasion. Front. Immunol. 2020;11:580641.
    20. Pavone P, Ceccarelli M, Marino S, Caruso D, Falsaperla R, Berretta M, Rullo EV, Nunnari G. SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome. Lancet Child Adolesc Health. 2021 Jun;5(6):e19-e21.
    21. Barizien, N., Le Guen, M., Russel, S. et al. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep. 2021;11:14042. https://doi.org/10.1038/s41598-021-93546-5
    22. Akbas MA, Akbas N. Adrenal Insufficiency in the Covid-19 Era. Am J Physiol Endocrinol Metab 320: E784–E785, 2021.
    23. Lui DTW, Lee CH, Chow WS, et al. Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?. Endocr Pract. 2021;27(9):894-902. 
    24. Khoo B, Tan T, Clarke SA, et al. Thyroid Function Before, During, and After COVID-19, J Clin Endocrinol Metab. 2021;106(2):e803-e811.
    25. Afrin LB, Weinstock LB, Molderings GJ. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020 Nov;100:327-332. 
    26. Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 ‘long-haulers’?.Chronic Dis Transl Med. 2021;7(1):14-26.
    27. Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A. COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?. Lancet. 2020;395(10239):1758-1759. 
    28. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens. 2021;10(6):763.
    29. Kinderlehrer DA. Is Bartonella a Cause of Primary Sclerosing Cholangitis? A Case Study. Gastrointest Disord. 2020;2(1):48-57.
    30. Biberfeld G. Autoimmune reactions associated with Mycoplasma pneumoniae infection. Zentralbl Bakteriol Orig A. 1979;245(1-2):144-149.
    31. https://www.yalemedicine.org/news/vaccines-long-covid (Accessed January 21, 2022) 
    32. Taefehshokr N, Taefehshokr S, Hemmat N, Heit, B. Covid-19: perspectives on innate immune evasion. Front. Immunol. 2020;11:580641.
    33. Vibholm LK, Nielsen SSF, Pahus MH, et al. SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine. 2021;64:103230. 
    34. Sun J, Xiao J, Sun R, et al. Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Emerg Infect Dis. 2020;26(8):1834-1838.
    35. Kinderlehrer, D.A. Recovery From Lyme Disease: The Integrative Medicine Guide to Diagnosing and Treating Tick-Borne Illness, Skyhorse Publishing, 2021, p.15-30.