Long COVID, the Heart, Cardiovascular System, and a Holistic Approach
INTEGRATIVE HEALTH
Lynn Toohey
PhD
This dysfunction in the nervous system is termed dysautonomia.
Long COVID is an often-debilitating illness that occurs in at least 10% of COVID viral infections (conservative estimate), and more than 200 symptoms have been identified with impacts on multiple organ systems. However, the most astounding fact is that the subjects who suffered a harsh, acute immune attack are not at high risk for long COVID symptoms; those with mild cases seem to suffer the most from after-effects.
This is an important factor to keep in mind because at least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily, and supportive protocols are not the same as the initial infection. The damage of long COVID has predominantly been attributed to immune-mediated response and chronic inflammation, rather than direct infection of cells by the virus. The initial attack may have been a brutal attack on the immune system, but in the aftermath of infection, the biggest problems of long COVID result from the organ damage or inflammation that the virus inflicted, or in some cases, suspected continual presence of the virus, especially in the gut or nervous system, which has been documented. Early research shows an increasing risk of long COVID sequelae after the second and third infection, with no protection in double-vaccinated and triple-vaccinated people. (Bowe, B„ xie, Y. & AI-Aly, Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat. Med. https://doi.org/10.1038/s41591... 2022.) Long
COVID patients do not necessarily have the underlying risk factors that plagued more susceptible people who caught COVID early on before less virulent strains came around. The important thing is that protocols for long COVID must address inflammation and organ damage rather than an abrupt immune attack.
Another important factor is that since the major focus was on respiratory symptoms when COVID hit, many think that research in other areas where organ damage occurred has suffered as a result, e.g., the heart and cardiovascular system. To add to that, the tests being used lack in specificity for long COVID, and many negative test results leave the mistaken impression that everything is okay, when in reality, scientists are continually trying to develop better and more efficacious tests that would actually pinpoint long COVID sufferers sooner and increase the probability of relief for those people.
Let’s focus on the heart with examples of long COVID symptoms and what is involved with people experiencing them.
Suspected Causes: There are multiple suspected causes of long COVID, such as disturbance of the hypothalamus-pituitary adrenal (HPA) axis, mitochondrial damage, etc. In the case of the circulatory system, microvascular blood clotting and dysfunction of both endothelial cells and signaling in the brainstem is of particular interest. Viral persistence is a viable theory for causing long COVID, and viral proteins or RNA have been found in the cardiovascular system, along with the gut, nervous system, reproductive system, brain, muscles, eyes, lymph nodes, appendix, breast tissue, hepatic tissue, lung tissue, plasma, stool, and urine. (Goh, D. etal. Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19. Preprint at https://www.researchsquare.com... article/rs-1379777/vl (2022)
COVID Sequelae: As mentioned, most long COVID cases are in non-hospitalized patients with a mild acute illness. This was noted in a recent review article published in January 2023 (Davis HE, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Jan 13:1-14.)
The full review article is available online by googling PubMed and simply putting “long COVID AND Davis” in the search bar. Among other organ attacks, the article reports on cardiovascular events, specifically POTS (postural orthostatic tachycardia syndrome). Studies show endothelial dysfunction, blood flow abnormalities, and metabolic changes (even in individuals with long COVID whose POTS symptoms abate), (van Campen, c. L.M. C. & Visser, F. C. Long-Haul COVID patients: prevalence of POTS are reduced but cerebral blood flow abnormalities remain abnormal with longer disease duration. Healthcare 10, 2105 2022.)
One of the most COVID-vulnerable organ systems is the autonomic nervous system, both sympathetic and parasympathetic, thus affecting heart and vessel function. This dysfunction in the nervous system is termed dysautonomia. When downstream COVID effects hit the sympathetic nervous system, it adversely affects the heart and circulatory system. POTS is an example of where there is a tilt table test to determine its presence, but in most cases, standard tests do not diagnose long COVID, and the negative results give a false security that everything is okay.
Mitochondria (our energy-producing cells) are hit hard by COVID, and in addition to resulting in a chronic fatigue situation, there is an insufficient amount of energy for the heart and cardiovascular system to function correctly. Resulting problems include impaired oxygen extraction, which, interestingly enough, may explain why exercise, normally thought to be standard therapy for fatigue, can actually make symptoms of fatigue
Worse. (Heerdt, P. M., Shelley, B. & Singh, I. Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications. Br. J. Anaesth. 128, e246-e249 2022; Wright, J., Astill, S. L. & Sivan, M. The relationship between physical activity and Long COVID: a cross-sectional study. Int. J. Environ. Res. Public Health 19, 5093 2022.)
The long-term circulatory system disruption caused by COVID includes a lot of downstream effects and increases risks of deep vein thrombosis, pulmonary embolism, and bleeding events. (Katsouiaris, i. et al.
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort
study, BMJ 377, e069590 2022.) Additionally, changes to the size and stiffness of blood cells have also been found, with the potential to affect oxygen delivery. Reduction in vascular density is reported to be long-lasting, specifically affecting small capillaries, and was discovered in long COVID patients 18 months after infection.
(Osiaevi, I. et al. Persistent capillary rarefication in long COVID syndrome. Angiogenesis https://doi. org/10.1007/s 10456-022-09850-9 (2022.)
An analysis of the U.S. Department of Veterans Affairs databases (VA data), including more than 150,000 individuals one year postCOVID, indicated a significantly increased risk of a variety of cardiovascular diseases, such as heart failure, dysrhythmias, and stroke, independent of the severity of initial COVID-19 presentation. (Xie, Y.,
Xu, E., Bowe, B. & Al-Aly, Z. Long-term cardiovascular outcomes of COVID-19. Nat. Med. 28,
583-590 (2022.) Cardiac MRI research has revealed cardiac impairment in 78% of 100 individuals who had a prior COVID-19 episode (investigated an average of 71 days after infection) and in 58% of participants with long COVID (studied 12 months after infection), confirming that these cardiac abnormalities are widespread and of long duration.
(Roca-Femandez, A. et al. Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection. Eur. Heart J. 43, ehac544.219 2022.)
The Gut Connection: Addressing the gut is important, even when talking about cardiovascular effects, because the gut microbiota composition is significantly altered in COVID patients, and the microbiota regulate the microbiota-gut-brain axis that dramatically affects the sympathetic nervous system. The gut is one of COVID’s biggest targets. SARS-CoV-2 RNA antigen persistence, discussed earlier, presents mostly in the gut mucosa and the nervous system. Presence in the gut increases the incidence of fungal translocation to other areas of the body and has been found in the plasma of long COVID patients, with the risk of inducing inflammatory Cytokines. (Giron, L. B. et al. Markers of fungal translocation are elevated during postacute sequelae of SARS-CoV-2 and induce NF-kB signaling. JCI Insight https://doi.org/10.1172/jci. insight. 160989 2022.) Long COVID subjects have dysbiosis with much lower levels of the good bacteria. (Liu, Q.
The gut is one of COVID’s biggest targets.
SARS-CoV-2 RNA antigen persistence, discussed earlier, presents mostly in the gut mucosa and the nervous system.
et al. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut 71, 544-552 2022.) Transferring gut bacteria from patients with long COVID to healthy mice (fecal microbiota transplantation, or FMT) resulted in lost cognitive function and impaired lung defenses in the mice.
(Mendes de Almeida, V. Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome. Res. Sq. https://doi.org/10.21203/ rs.3.rs-1756189/vl 2022.) This emphasizes the fact that probiotics are always a helpful supplement for COVID sequelae. In fact, studies support the use of probiotics for long COVID support. (Zhang, L. et al. Gut micro-biota-derived synbiotic fonnula as a novel adjuvant therapy for COVID-19: an open-label pilot study. J. Gastroenterol. Hepatol. 37, 823-831 2022.)
“Probiotics also help increase vitamin D absorption and expression, which is important post-COVID-19 as suboptimal vitamin D levels have been associated with hyperinflammatory cytokine production”. (Thomas R, et al..
A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Concentrated Phytochemical-Rich Nutritional Capsule in Addition to a Probiotic Capsule on Clinical Outcomes among Individuals with COVID-19—The UK Phyto-V Study. COVID. 2022: 2(4):433-449.)
Diagnostic Tools and Treatments: Although diagnostic tools exist for some components of long COVID (for example, the previously mentioned tilt table tests for POTS and MRI scans to detect cardiovascular impairment), diagnostic tools for long COVID are mostly in development, including imaging to detect microclots, new fragmentation of QRS complex on electrocardiograms that indicate cardiac injury, and use of hyperpolarized MRI to detect pulmonary gas exchange abnormalities. On the basis of the tests offered as standard care, the results for patients with long COVID are often normal; many providers are unaware of the symptom-specific testing.
The Holistic Support: Of course, many nutrients can be helpful, but in this article, I’d like to focus on the ones mentioned by the comprehensive review article from January of this year (Davis HE, et al. Long COVID:
major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Jan 13:1-14.) The researchers reported that “some supplements have shown promise” in supporting long COVID, “including coenzyme Q10 and d-ribose.” The review authors also noted that pycnogenol statistically significantly improved physiological measurements (for example, reduction in oxidative stress) and quality of life (indicated by higher Karnofsky Performance Scale Index scores). Since grape seed extract basically contains the same proanthocyanidins as pycnogenol but is a much cheaper source for these super plant chemicals, grape seed extract is usually the nutrient of choice.
CoQlO and the Heart: The heart is a muscle that uses a significant amount of ATP (energy) to pump blood through the body’s vessels with each contracture. Increased blood levels of CoQlO levels were found to support heart function in children who needed cardiac muscle support. CoQlO is a lipid-soluble nutrient that participates in energy synthesis and considered good support for cardiac muscle. (Nutrients. 2018 Nov 7;10(11). pii: E1697. APilot Clinical Study of Liquid Ubiquinol Supplementation on Cardiac Function in Pediatric Dilated Cardiomyopathy. Chen FL. et al.) CoQlO
has also been found to be excellent support for the energy needed to provide a healthy ejection fraction from the
heart. (JACC Heart Fail. 2014 Dec;2(6):641-9. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. Mortensen SA, et al.) A tWO-year randomized, double-blinded trial of420 patients determined that long-term CoQlO treatment of patients in heart imbalance was found to be safe, beneficial, and supportive of normal heart function. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomized, double-blind, multicenter trial with focus on Symptoms, Biomarker status Brain-Natriuretic Peptide (BNP))
D-Ribose and the Heart: D-Ribose supports ejection fraction, diastolic function (energy-dependent), and heart integrity, including the heart’s ability to do its job and pump blood to circulate throughout the body. (TherAdv Cardiovasc Dis. 2015 Jun;9(3):56-65.)
Lack of oxygen in the heart leads to lower cellular energy levels, and that affects a cell’s integrity and function. Preclinical studies have reported lower cellular energy levels with an associated decreased function following lowered oxygen levels in the heart. Scientists have reported that a dysfunctional heart is energy starved. D-ribose, a natural occurring carbohydrate, has demonstrated significant enhancing abilities in replenishing deficient cellular energy levels and guiding dysfunction back to homeostasis following lowered oxygen levels in
the heart. (Recent Pat Cardiovasc Drug Discov. 2010 Jun;5(2):138-42. The patented uses of D-ribose.... Shecterle LM(1), Terry KR, St Cyr JA.)
When cellular processes are compromised by a decrease in energy levels, it is ultimately reflected in altered function. “Ribose appears to provide a solution to the problem in replenishing the depressed ATP levels and improving functional status of patients”. (J Diet Suppi. 2008;5(2):213-7. Ribose in the heart. Herrick J, St Cyr J.)
Fish Oil and the Heart and Long COVID: Since the 2023 article review by Davis et al. focused on the fact that long COVID deserves special attention because of the inflammation and organ damage that ensues, fish oil (with a high concentration of EPA and DHA) should be considered because of the overwhelming scientific evidence showing its support in an inflammatory environment.
In a specific study of fish oil and long COVID, “The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long-chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress, and psychoneuroimmunity at different stages of SARS-CoV-2 infection”21. In that study, scientists go on to reveal that omega-3 PUFAs, particularly EPA, have shown positive support effects by reducing pro-inflammatory cytokines, balancing the HPA axis, and modulating neurotransmission. In addition, omega-3 PUFAs and their metabolites are involved in the homeostatic process of cleansing chronic inflammation and “restoring tissue homeostasis,” therefore offering a “promising strategy for long COVID.” The researchers pondered “the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID...”. (Yang CP, et al. Long
COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19. Brain Behav Irnmun. 2022 Jul;103:19-27.)
In conclusion, it is impossible to name all the nutrients that are helpful for long COVID support, but that is one reason this is an ongoing article series. This particular installment on COVID sequelae that affect the heart was inspired by the very recent review on long COVID this year (2023) by Davis et al. The important take-home message from that article was that long COVID symptoms are not tied to a severity of the immune attack, that they can increase with each occurrence of infection, that they are still developing diagnostic tests for it, and that there are holistic support recommendations to help.
Dr. Lynn Toohey organizes seminars, acts as a nutritional consultant to Nutri-West (www.nutriwest. com) and authored the Functional Health Evaluation program that analyzes blood tests and DNA raw data (www.FHEcloud.com). Dr. Toohey can be reached at [email protected] with any questions.
