While none of us like to hear the newest, a-bit-longer-than-four letter curse word, COVID, research into the pathophysiology or mechanisms of acute and chronic COVID illness has helped us understand Lyme disease better. Clinical experience in adult and pediatric functional medicine clinics confirms that both of these debilitating diseases work through common inflammatory pathways. In some cases, COVID or its vaccine have even triggered Lyme relapses. At the end, I will discuss how to tell the difference and whether knowing the difference impacts treatment approach. While we may groan when thinking of either of these diseases, their combination does not have to leave us in despair if we know how to combat their common underlying mechanisms.
SARS-CoV2, the virus behind the diseases we call acute COVID19 and Post COVID syndrome, shares an impressive number of common pathways with Lyme disease, but a few of its peculiar mechanisms are worth looking at first. Probably the most noteworthy mechanism by which SARS-CoV2 causes its own set of pathological changes is its interaction with the ACE2 on cells. This angiotensin converting enzyme number 2 (ACE-2) normally interacts with blood borne chemical messengers regulating blood pressure and inflammation. When the SARS CoV2 virus hijacks ACE2 for cell entry, less is available for normal functions. This contributes greatly to not only lung dysfunction but other organ dysfunction or failure as well.
Aside from this differing mechanism, the cytokine cascade triggered by SARS CoV2 very much resembles that of tick-borne diseases like Lyme from Borrelia. As the prior essay describing the mechanisms of Lyme disease outlined the multiple pathways by which Borrelia triggered disease, COVID also triggers this cascade. Acute COVID results in a much greater cascade intensity, but chronic Lyme and Post-COVID Syndrome overlap in cytokines and their levels.
Transforming growth factor beta (TGF-beta) may rise as we see with Lyme disease (and mold toxicity as well). Matrix metalloproteinases can increase leading to tissue destruction. The p38 – MAPK pathway usually elevates. Interleukins 10, 4, 1B, and 6 can rise as well (Lu et al, 2021; Gelzo, 2022).
Returning to the entry of the virus by way of the ACE-2, we note that by blocking the normal function of ACE2, the ACE2 cannot convert angiotensin II into angiotensin 1-7. The build-up of angiotensin II activates the p38 – MAPK pathway (Beyerstedt, 2022) which then triggers elevations of IL-6, TNF-alpha, and IL-1B (Grimes, 2020).
From there, we can trace the effects of these different cytokines and their downstream effects. IL-6 serves as a primary driver of fever as it serves multiple roles in the body. The production of other inflammatory cytokines are triggered by IL-6 including CD4, IL21, CD8 as well as B cells. Meanwhile it turns down T reg cells which normally control excessive inflammation and immune activation (Potere, 2021).
TGF-beta through its own elevation contributes to both symptoms and further dominoes. Elevated levels can decrease the amount of deep sleep one gets, slow the regeneration of muscles, lower bones density, slow red blood cell formation, lower Natural Killer cell activity, and cause other unpleasant effects on the immune system. Furthermore, it can increase free radical production, thereby increasing oxidative stress, and can increase blood vessel growth as well as fibrosis and contribute to the re-emergence of EBV virus (Ferreira-Gomes, 2021).
IL-6 along with TNF-alpha and IL -1 beta play the primary role in long COVID symptoms. TNF-alpha contributes to the pathology of COVID by furthering inflammation. It amplifies the responses to environmental stressors and recruits more inflammatory cells to an area. IL-1 beta drives inflammation and helps one recover in acute infections, but in situations of persistently high levels it can lead to autoimmune diseases as well as tumor development (Mardi, 2021). IL-6 was discussed above.
The last molecule which plays a role in both Lyme and Post COVID is one that few have likely heard of before. Galectin – 3 serves a role in modulating inflammation in our bodies under normal circumstances. Interestingly, the spike protein of SARS CoV2 closely resembles Galectin – 3. In a study, higher levels of Galectin – 3 in acute COVID patients correlated with severity of disease leading to ICU admission and death (Caniglia, 2020). Dr. Hinchey took a few minutes to describe how a product her company sells can lower the inflammatory response caused by spike protein’s chronic activation of Galectin – 3. She provided mechanisms of action and research studies to support her advocacy for the use of modified citrus pectin to break the chronic inflammation cycle.
With the shared mechanisms between Lyme described in the last essay and COVID in this essay, it is no wonder that the symptoms they cause resemble each other. It is also not surprising that COVID or vaccination to COVID can trigger a relapse of Lyme disease that had been dormant. In terms of cytokines altered by Lyme and COVID, the only thing they don’t share is tick saliva and flagellin. From there, the other cytokines are basically identical. From these shared pathways, they both trigger symptoms of fatigue, brain fog, sweats, headache, sleep problems, dizziness, pains, palpitations and more. Even routine labs may overlap as both can cause false positive anti-nuclear antibodies, false positive rheumatoid factors, changes on brain imaging, anti-phospholipid antibodies, and more. The most noticeable differences are that COVID causes less musculoskeletal pain while Lyme disease is less likely to cause shortness of breath and loss of smell.
While the mechanisms by which COVID can reactivate Lyme disease are not elucidated, there are several theories. Given SARS CoV2’s propensity to cause inflammation and micro-clotting, the resulting tissue destruction likely provides Borrelia food sources to stimulate growth. Beyond that, imbalances in the Th1 and Th2 arms of the immune system as well as the elevations in shared cytokine pathways likely make it easier for Lyme to reawaken from dormancy.
So, when the rubber meets the road, what does a functional medicine doctor do when a patient with Lyme infection in remission reports their symptoms are returning after a bout with COVID? Many of the tests for Lyme activity overlap with Post COVID syndrome. So far, the two labs which may differentiate between the two are CD57 and C4a, which are respectively lower and higher in Lyme but less effected by post-COVID. Regardless, the first response is to turn down the biotoxin inflammation pathway with therapies like glutathione, vitamin C, resveratrol, quercetin, curcumin, and SPM Actives. From there, if the inflammation seems to be improving, but Lyme-like symptoms of migratory pain persist, then we return to dealing with the Lyme infection.
Helping our patients return to healthier more abundant lives also requires secondary recoveries after COVID sets patients back a step. Many of our Lyme recovered patients are impressed with how easy they made it through COVID, but some need that secondary response to get them back to their regained healthier life.
PS: Dr. Hinchey’s talk went much deeper at the conference and is a worthwhile investment if you want to attend her upcoming Lyme conference found on LymeBytes website.
***Welcome to the eighth essay in our special series sharing insights and recent research from the MEDMAPS 2023 Spring Conference attended by Dr. Potter. MAPS stands for Medical Academy for Pediatric Special Needs and arose from the original Defeat Autism Now organization initially serving parents and providers caring for children with autism spectrum disorder). This Spring Conference focused not only on autism research but on Lyme and other infections including COVID’s effects on children. Come back in the coming weeks to read more about what I learned at the conference so that Sanctuary can provider cutting edge care to your precious little ones.***
Medical Disclaimer: These essays are for educational purposes only. We assume no responsibility for your choice to implement something from these essays. Even if you are a patient of our clinic, you should consult with us before adding therapies. If you are not one of our patients, talk with your health care provider before trying any of these therapies.
Bibliography
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Gelzo, M., Cacciapuoti, S., Pinchera, B. et al. Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients. Sci Rep 12, 1212 (2022). https://doi.org/10.1038/s41598-021-04677-8
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Potere, Nicola, Alberto Batticciotto, Alessandra Vecchié, Ettore Porreca, Antonella Cappelli, Antonio Abbate, Francesco Dentali & Aldo Bonaventura (2021) The role of IL-6 and IL-6 blockade in COVID-19, Expert Review of Clinical Immunology, 17:6, 601-618, DOI: 10.1080/1744666X.2021.1919086
Ferreira-Gomes, M., Kruglov, A., Durek, P. et al. SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself. Nat Commun 12, 1961 (2021). https://doi.org/10.1038/s41467-021-22210-3
Mardi, Amirhossein, Sepideh Meidaninikjeh, Sepideh Nikfarjam, Naime Majidi Zolbanin, and Reza Jafari. Interleukin-1 in COVID-19 Infection: Immunopathogenesis and Possible Therapeutic Perspective. Viral Immunology. Dec 2021.679-688.http://doi.org/10.1089/vim.2021.0071
Caniglia, J. L., Guda, M. R., Asuthkar, S., Tsung, A. J., & Velpula, K. K. (2020). A potential role for Galectin-3 inhibitors in the treatment of COVID-19. PeerJ, 8, e9392. https://doi.org/10.7717/peerj.9392
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.
