Richard Horowitz MD, May Awareness Guest Blog – Lyme Disease & COVID-19

Those of us who have been on the front line of the Lyme epidemic for decades, watching patients get sick with acute and chronic forms of the illness, are in a unique position to help find solutions for the COVID pandemic. Both diseases have acute and chronic forms with clinical pictures that strongly resemble each other, with imperfect testing strategies. Lyme and COVID can lead to acute and/or chronic fatiguing, musculoskeletal illnesses, and neuropsychiatric difficulties, with similar multisystemic manifestations. These include fevers, sore throats, headaches, hair loss, chest pain, shortness of breath, gastrointestinal complaints, joint/muscle/and nerve pain, brain fog, insomnia, dizziness, palpitations, anxiety, depression and on rare occasions, even psychosis. Establishing a proper diagnosis for both illnesses is essential because both diseases mimic each other, can simultaneously exist, and treatments are completely different. Also, chronic Lyme and long COVID are also presently mired in scientific mystery and debate. Perhaps unraveling the mystery of long COVID, a disease with similar manifestations to CLD/PTLDS, will allow us to find novel solutions to both illnesses. Why?

The symptoms of COVID and Lyme disease resemble each other, because in both illnesses the 3 I’s, infections, inflammation, and immune dysfunction, are at the root cause of both acute and chronic manifestations. The differences clinically are primarily around Lyme having a migratory component to pain (not seen in COVID)[1], with symptoms that come and go, responding or worsening (Herxheimer reaction) with antibiotics. The Delta variant also caused a loss of sense of smell and/or taste, which is usually seen with viral infections and neurodegenerative illness like Alzheimer’s dementia.

When the COVID pandemic first emerged in early 2020, I reviewed the biochemistry of how the virus was making people sick. It looked similar to Lyme. The virus stimulated an inflammatory pathway inside the nucleus of the cell, called NFKappaB, while downregulating an anti-inflammatory pathway, called Nrf2. People were getting sick because of cytokine storms and increased inflammatory molecules like TNF-alpha, IL-1b and IL-6, leading to immune reactions that were wreaking havoc on the internal organs of the body, especially the lungs, heart, brain, and kidney. Those of us in the Lyme field know these cytokines well because they are part of Herxheimer reactions that Lyme patients frequently experience while killing off spirochetal infections. I had already used NAC, alpha lipoic acid, and glutathione effectively in thousands of Lyme patients for Herxheimer reaction. These agents help block NFKappaB, and published those results in both of my books, Why Can’t I Get Better[2], and How Can I Get Better [3]. Using a translational medicine approach, taking what I learned from Lyme, we published the first scientific paper in the world literature on the use of glutathione and nutraceuticals to help modulate the COVID disease process[4]. Glutathione had helped to decrease acute symptoms in COVID pneumonia, and that paper has now been cited by other researchers over 160 times. To date, we have effectively treated over 125 acute COVID cases with that protocol (see: www.cangetbetter.com under the COVID tab) with no associated mortality, including some efficacy in a small number of longhaulers who came to us from other medical practices. Since our publications in 2020, regimens we have used for chronic Lyme, including zinc, Vitamin D, melatonin, curcumin and sulforaphane glucosinolate, apart from glutathione and NAC, have all been published as potential adjunctive therapies to decrease viral inflammation in COVID [5] [6] [7].

Our glutathione paper was followed up by a publication in Medical Hypothesis, discussing three novel prevention, diagnostic and treatment options for COVID-19 urgently necessitating controlled randomized trials[8]. We have applied for an FDA IND (Investigational New Drug) for glutathione in COVID, as it has both anti-viral and anti-inflammatory properties, and we have been approved for a randomized, controlled trial of glutathione in long COVID at the University of California, Irvine. The study will evaluate multiple potential etiologies in longhaulers, i.e., the same 16-point MSIDS variables we have been finding to play a role in chronic Lyme[9]. To date, reactivation of infections (like EBV), Postural Orthostatic Tachycardia Syndrome, i.e., POTS/dysautonomia, autoimmunity and mitochondrial dysfunction have all been found to play a role in those suffering from long COVID, i.e., at least 4/16 MSIDS variables [10] [11] [12] [13]. In our upcoming study at UCI, we will also be evaluating the potential role of underlying hormonal dysfunction (including low adrenal function), toxins (heavy metals, mold) and tick-borne infections. Since elevated VEGF is being found in longhaulers through Bruce Patterson’s lab and cytokine panel [14], it is possible that reactivation of bartonella may be playing a role in some chronically ill individuals. Stay tuned for that one!

Billions of dollars are now being spent on determining the etiology of long COVID. Compare the $15.6 billion allotment for NIH research on COVID to the pitiful $50 million for Lyme research. Despite the small allocation for Lyme disease research, the money for COVID could benefit the Lyme community, long denied support because of dysfunctional LD politics. Validation of chronic diseases like CFS/ME, Fibromyalgia and Chronic Lyme have been woefully lagging within the past few decades (over 5% of the US population suffers from these illnesses), and validation of long COVID, and its multiple etiologies, should help validate and improve the understanding of those suffering with CLD and other chronic fatiguing illnesses. The stigma surrounding Lyme disease has hampered many patients from getting proper care, and as long COVID is validated as a ‘real illness’ and not psychosomatic in nature, we should be able to bridge coronavirus research and apply it to tick-borne illness. As an example, recently the coronavirus was found to persist in certain hidden areas of the body[15]. Up until several years ago, we didn’t know that borrelia could hide from the immune system and form dormant persister cells in biofilms leading to inflammation and chronic illness[16]. The work we have been doing using persister drugs like dapsone and disulfiram is finally providing novel solutions for a significant number who have led lives of pain and suffering. Many patients in our practice who have completed those protocols are now in long term remission as long as overlapping MSIDS variables have been properly addressed[17].  

A comprehensive exploration of one infectious illness, COVID-19, that has brought widespread suffering and death to millions of individuals, may ultimately bring some relief to our beleaguered Lyme and tick-borne patients, as both diseases may present with persistence and reactivation of infection with multiple overlapping inflammatory pathways and downstream effects. The time has come for the broader medical community to benefit from our 30+ year experience treating chronically ill Lyme patients, whose symptoms mimic long COVID, and conversely, we might now benefit from the extensive research being done on coronaviruses, exploring the multifactorial etiologies underlying mechanisms of chronic illness.

Disclaimer: The views in this article are those of Dr Richard Horowitz, and do not represent the views of the TBDWG, HHS or the United States.

[1] Empirical Validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for Suspected Lyme Disease. Maryalice Citera, Ph.D., Phyllis R. Freeman, Ph.D., Richard I. Horowitz, M.D., International Journal of General Medicine 2017:10 249–273

https://www.dovepress.com/empirical-validation-of-the-horowitz-multiple-systemic-infectious-dise-peer-reviewed-fulltext-article-IJGM

http://www.ncbi.nlm.nih.gov/pubmed/28919803

[2] Why Can’t I Get Better? Solving the Mystery of Lyme and Chronic Disease. Dr Richard I. Horowitz. St Martin’s Press, NYC. Publication date November 2013. HC ISBN-13: 978-1-250-01940-0

ISBN-10: 1-250-01940-0, 6 1/8 9 ¼ ● 526 pages

[3] How Can I Get Better? An Action Plan for Treating Resistant Lyme and Chronic Disease. St Martin’s Press, NYC, publication date February 2017 How Can I Get Better?  Richard Horowitz, M.D.. HC ISBN 978-1-250-07054-8 (hardcover) ISBN 978-1-250-11144-9 (e-book)

[4] Horowitz, R.I., Freeman P, Bruzzese, J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respiratory Medicine Case Reports, April 21, 2020. Article Number: 101063 https://doi.org/10.1016/j.rmcr.2020.101063

[5] Kaya MO, Pamukçu E, Yakar B. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies. Epidemiol Health. 2021;43:e2021074. doi: 10.4178/epih.e2021074. Epub 2021 Sep 23. PMID: 34607398; PMCID: PMC8769802.

[6] Sethuram, R., Bai, D. & Abu-Soud, H.M. Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction. Reprod. Sci. 29, 1–6 (2022). https://doi.org/10.1007/s43032-020-00400-6

[7] Ordonez, A.A., Bullen, C.K., Villabona-Rueda, A.F. et al. Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice. Commun Biol 5, 242 (2022). https://doi.org/10.1038/s42003-022-03189-z

[8] R.I. Horowitz, P.R. Freeman, Three Novel Prevention, Diagnostic and Treatment Options for COVID-19 Urgently Necessitating Controlled Randomized Trials, Medical Hypotheses (2020)https://www.sciencedirect.com/science/article/pii/S0306987720308276?via%3Dihub

[9] Horowitz, R.I.; Freeman, P.R. Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2. Healthcare 2018, 6, 129.

https://www.ncbi.nlm.nih.gov/pubmed/30400667

[10] Varanasi S, Sathyamoorthy M, Chamakura S, Shah SA. Management of Long-COVID Postural Orthostatic Tachycardia Syndrome With Enhanced External Counterpulsation. Cureus. 2021 Sep 30;13(9):e18398. doi: 10.7759/cureus.18398. PMID: 34729276; PMCID: PMC8555928.

[11] Rojas M, Rodríguez Y, Acosta-Ampudia Y, Monsalve DM, Zhu C, Li QZ, Ramírez-Santana C, Anaya JM. Autoimmunity is a hallmark of post-COVID syndrome. J Transl Med. 2022 Mar 16;20(1):129. doi: 10.1186/s12967-022-03328-4. PMID: 35296346; PMCID: PMC8924736.

[12] Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Jeffrey E. Gold, et al. Pathogens. 2021 Jun; 10(6): 763. Published online 2021 Jun 17. doi: 10.3390/pathogens10060763

[13] De la Cruz-Enríquez J, Rojas-Morales E, Ruíz-García MG, Tobón-Velasco JC, Jiménez-Ortega JC. SARS-CoV-2 induces mitochondrial dysfunction and cell death by oxidative stress/inflammation in leukocytes of COVID-19 patients. Free Radic Res. 2021 Oct;55(9-10):982-995. doi: 10.1080/10715762.2021.2005247. Epub 2021 Dec 5. PMID: 34866537.

[14] Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Bruce K. Patterson1 et al. (IncellDx Inc, San Carlos, CA, United States) Front. Immunol., 28 June 2021 | https://doi.org/10.3389/fimmu.2021.700782

[15] Desimmie BA, Raru YY, Awadh HM, He P, Teka S, Willenburg KS. Insights into SARS-CoV-2 Persistence and Its Relevance. Viruses. 2021 May 29;13(6):1025. doi: 10.3390/v13061025. PMID: 34072390; PMCID: PMC8228265

[16] Horowitz, R.I., Murali, K., Gaur, G. et al. Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi. BMC Res Notes 13, 455 (2020). https://doi.org/10.1186/s13104-020-05298-6. https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-020-05298-6?fbclid=IwAR0qt8lyjHfOYlC_Z5k_a4DGxa49sYned_6xC8mRz66m2Wirekb0MX0vBRA#citeas

[17] Horowitz, R.I.; Freeman, P.R. Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retrospective Chart Review. Antibiotics 2020, 9, 725. https://doi.org/10.3390/antibiotics9110725