Viral diseases, like SARS-CoV-2, are known for their ability to hijack and destabilize the intracellular environment, creating conditions that are favorable for their replication.The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Mitochondrial disorders are a complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain aka Krebs Cycle), which in some patients can lead to an unexplained post-viral illness, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In fact, the first analysis of a prospective observational study of patients who remained ill six months after mild or moderate acute SARS-CoV-2 found that about half met criteria for ME/CFS. What have researchers discovered about the possible link between post-acute sequelae of SARS-CoV-2 infection (PASC), mitochondrial dysfunction, and ME/CFS?
Research on the long-term effects of SARS-CoV-2 continues to indicate that a substantial number of individuals experience lasting symptoms after the initial infection has been cleared, including psychiatric disorders and neurocognitive decline. Autopsies of patients confirm the presence of the coronaviruses in the central nervous system (CNS), especially in the brain. Follow-ups conducted in Germany and the United Kingdom found what they have come to label "post-acute sequelae of Sars-CoV-2 infection," or PASC for short, neuropsychiatric symptoms in 20-70% of patients, including young adults. Multiple studies have shown that SARS-CoV-2 can directly or indirectly affect the CNS, and some patients experience a component of cognitive dysfunction, called “brain fog,” which includes psychological symptoms such as difficulty concentrating, forgetfulness, confusion, behavioral changes, depression, and fatigue. Relapse or recurrence of these symptoms may be triggered by stress.
Scientists hypothesize that both direct and indirect mechanisms may contribute to the development of these symptoms, which are similar to those experienced by patients with ME/CFS and are often linked to mitochondrial dysfunction. Furthermore, some studies suggest that the neuropsychiatric manifestations of PASC may also lead to an increased additional long-term risk of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.
This all sounds a bit scary, I know, but there's also an opportunity for enlightened intervention coming...
A 2022 study on 50 patients provided the first evidence of mitochondrial dysfunction in PASC syndrome. And while the mechanisms by which SARS-CoV-2 may disrupt mitochondrial metabolism is unknown, researchers have developed several hypotheses. Yet another team of researchers concluded that a sustained decrease of the mitochondrial membrane potential may be related to PASC.
Focused Nutrition, with Perhaps Targeted, Short-Term Supplementation, May Be the Most Effective Plan for Mitochondrial Impairment in Long Covid
For those willing to try it, the IFM's Mitochondrial Food Plan, plant forward (but not veg or vegan) and antioxidant rich, is an anti-inflammatory, low-glycemic, high-quality fat dietary approach that supports healthy mitochondria for improved energy production.
Supplement-wise, the latest research & knowledge short list the following, although it is difficult and perhaps foolhardy to make generalized recommendations.
Especially where mitochondrial health is concerned, the kind of "biggest bang for you buck" approach, at least imo, would be to do something like Genova Diagnostics NutrEval comprehensive evaluation (you want the Plasma one; not the FMV (urine) one): that gives you not only a real-time look at all these essential nutrient levels but also a window into any toxin exposures that could be interfering with either mitochondrial function or healing.
You can order a test kit (for yourself, for a loved one, for the entire family!) from sites like Rupa Health, True Health Labs and ($559) even sites like Direct Labs ($489)-- although some won't ship to addresses in NY. You can also ask us for a kit ($379). It entails both a blood draw and a (first morning) urine sample, express shipped in a Styrofoam container with an ice pack-- all included. Here's a sample Results Overview summary page:
And one page breaking down sufficiency/insufficiency of key antioxidant nutrients:
With that caveat, here is a general "redox support" nutrient list:
Antioxidant supplementation: Vitamins C and E, as well as selenium, to counteract excess ROS production (and help to recycle glutathione)
Plant-heavy eating plan: Diets high in plant defense compounds with pleiotropic actions that are known to modulate mitochondrial function and induce resolution of inflammation, as well as displaying anti-pathogen function
CoQ10 supplementation: Strategies to target mitochondrial bioenergetics and antioxidant defense include supplemental therapy with CoQ10, a crucial player in the mitochondria
Acetyl-L-carnitine (ALC, some people say "ALCAR"): ALC is key to mitochondrial function, promoting the expression of nerve growth factors and peripheral nerve regeneration and conduction
α-Lipoic acid (ALA): ALA, also known as thioctic acid, is a powerful antioxidant, acting as a coenzyme in mitochondrial reactions
Finally, to care for membranes, phosphatidylcholine + tocotrienols (maybe also with a little astaxanthin) is the way forward. I am particularly fond of Dr. Christopher Shade's Membrane Mend product, of his company Quicksilver Scientific. (Message me if this link doesn't work for you.) If you're up for doing the whole program, have a look at Membrane Renewal.
Studies/papers* of potential interest:
Elesela S, Lukacs NW. Role of mitochondria in viral infections. Life (Basel). 2021;11(3):232. doi:3390/life11030232
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. doi:1016/j.cdtm.2020.11.002
Kedor C, Freitag H, Meyer-Arndt L, et al. Chronic COVID-19 syndrome and chronic fatigue syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study. Preprint. medRxiv. Published February 8, 2021. Accessed August 4, 2022. doi:1101/2021.02.06.21249256
Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Front Med.2021;7:606824. doi:3389/fmed.2020.606824
Stefano GB, Büttiker P, Weissenberger S, et al. Biomedical perspectives of acute and chronic neurological and neuropsychiatric sequelae of COVID-19. Curr Neuropharmacol. 2022;20(6):1229-1240. doi:2174/1570159×20666211223130228
Pozzi A. COVID-19 and mitochondrial non-coding RNAs: new insights from published data. Front Physiol. 2022;12:805005. doi:3389/fphys.2021.805005
Swain O, Romano SK, Miryala R, Tsai J, Parikh V, Umanah GKE. SARS-CoV-2 neuronal invasion and complications: potential mechanisms and therapeutic approaches. J Neurosci. 2021;41(25):5338-5349. doi:1523/jneurosci.3188-20.2021
Carmona-Torre F, Mínguez-Olaondo A, López-Bravo A, et al. Dysautonomia in COVID-19 patients: a narrative review on clinical course, diagnostic and therapeutic strategies. Front Neurol. 2022;13:886609. doi:3389/fneur.2022.886609
Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. 2021;78(6):682-683. doi:1001/jamapsychiatry.2021.0500
Stefano GB, Ptacek R, Ptackova H, Martin A, Kream RM. Selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce ‘brain fog’ and results in behavioral changes that favor viral survival. Med Sci Monit. 2021;27:e930886. doi:12659/msm.930886
Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2021;118(34):e2024358118. doi:1073/pnas.2024358118
de Boer E, Petrache I, Goldstein NM, et al. Decreased fatty acid oxidation and altered lactate production during exercise in patients with post-acute COVID-19 syndrome. Am J Respir Crit Care Med. 2022;205(1):126-129. doi:1164/rccm.202108-1903le
Bachiller S, Jiménez-Ferrer I, Paulus A, et al. Microglia in neurological diseases: a road map to brain-disease dependent-inflammatory response. Front Cell Neurosci. 2018;12:488. doi:3389/fncel.2018.00488
Díaz-Resendiz KJG, Benitez-Trinidad AB, Covantes-Rosales CE, et al. Loss of mitochondrial membrane potential (Δψ m) in leucocytes as post-COVID-19 sequelae. J Leukoc Biol. 2022;112(1):23-29. doi:1002/JLB.3MA0322-279RRR
Leung B. Role of nutrients for COVID-19 recovery: an integrative approach. Eur J Integr Med. 2021;48:101978. doi:1016/j.eujim.2021.101978
Nunn AVW, Guy GW, Botchway SW, Bell JD. SARS-CoV-2 and EBV; the cost of a second mitochondrial “whammy”? Immun Ageing. 2021;18(1):40. doi:1186/s12979-021-00252-x
Sumbalova Z, Kucharska J, Palacka P, et al. Platelet mitochondrial function and endogenous coenzyme Q10 levels are reduced in patients after COVID-19. Bratisl Lek Listy. 2022;123(1):9-15. doi:4149/bll_2022_002
De Flora S, Balansky R, La Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J.2020;34(10):13185-13193. doi:1096/fj.202001807
Izquierdo JL, Soriano JB, González Y, et al. Use of N-acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19. Sci Prog. 2022;105(1):368504221074574. doi:1177/00368504221074574
Córdova-Martínez A, Caballero-García A, Pérez-Valdecantos D, Roche E, Noriega-González DC. Peripheral neuropathies derived from COVID-19: new perspectives for treatment. Biomedicines. 2022;10(5):1051. doi:3390/biomedicines10051051
Burtscher J, Burtscher M, Millet GP. The central role of mitochondrial fitness on antiviral defenses: an advocacy for physical activity during the COVID-19 pandemic. Redox Biol. 2021;43:101976. doi:1016/j.redox.2021.101976
* I can get full text reprints of most of these if full text is not offered at the publisher's (or National Library of Medicine /PubMed's) website.