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 diseases and translational medicine. 2021;7(1):14-26
Plain language summary
Cases of chronic fatigue have been reported following recovery from Covid-19, in what is termed ‘Long Covid’, with symptoms likened to that of sufferers from chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME). How CFS/ME develop and treatments may help to further understand Covid-19. This review study of 111 studies aimed to identify where urgent research is required to help understand the potential of chronic fatigue therapies in Covid-19. The study first reviewed disrupted cellular energy production in ME/CFS and increased presence of damaging oxidants. Current therapies for improving cellular energy production in CFS/ME were then reviewed and Ritalin, ubiquinone and mitoquinol mesylate were heavily featured. Antioxidant therapies in CFS/ME were reviewed and observations would suggest that trials in patients with long covid are needed. It was concluded that research in cellular energy production in CFS/ME has been increasing, however remains contradictory due to a lack of a definitive diagnosis, differing disease severity and the huge differences between patients who suffer from CFS/ME. Further research is required in ME/CFS and Covid-19. This study could be used by health care professionals to understand the importance of monitoring symptoms of fatigue post Covid-19 infection and the possible use of ME/CFS treatments.
A significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome. This study reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may play in the understanding of the pathophysiology and treatment of chronic fatigue. It describes what is known about the dysfunctional pathways which can develop in mitochondria and their relationship to chronic fatigue. It also reviews what is known about oxidative stress and how this can be related to the pathophysiology of fatigue, as well as examining the potential for specific therapy directed at mitochondria for the treatment of chronic fatigue in the form of antioxidants. This study identifies areas which require urgent, further research in order to fully elucidate the clinical and therapeutic potential of these approaches.
Western Dietary Pattern Antioxidant Intakes and Oxidative Stress: Importance During the SARS-CoV-2/COVID-19 Pandemic.
Advances in nutrition (Bethesda, Md.). 2021;12(3):670-681
Plain language summary
The Atlantic diet (AD), Mediterranean diet (MD) and diets which follow the American dietary guidelines (AmD) all supply enough nutrients for the body to stay healthy. However, during periods of viral pandemics, such as the Covid-19 pandemic, these diets may be inadequate for optimal resistance to infection. Furthermore, nutrient requirements may alter with age, stress, and health. This review paper aimed to discuss the three different diets and their suitability depending on age and physical and mental state. Supplementation during a pandemic was also discussed. When the body contracts viruses such as Covid-19, reactive oxygen species can accumulate resulting in oxidative stress which can damage the cells. Nutrients in the diet, which act as antioxidants may be of benefit, in this instance, however traditional balanced diets such as the AD, MD and AmD may be inadequate. In tandem with a balanced diet, supplementation may improve health. Zinc, vitamin A, selenium, vitamin D, vitamin C, and iron have been shown in research to improve the body’s response to viruses. It was concluded that the Covid-19 pandemic has caused severe infections, which can result in oxidative stress, increasing vulnerability to viral infections. Supplementing certain nutrients may be of benefit especially in vulnerable individuals. This study could be used by healthcare professionals to understand that a balanced diet is essential during viral pandemics, and it may be necessary to consider supplementation for high-risk individuals.
The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.
Dissecting the interaction between COVID-19 and diabetes mellitus.
Journal of diabetes investigation. 2020;11(5):1104-1114
Plain language summary
Several countries have reported higher death rates and more severe cases of covid-19 amongst individuals with chronic diseases such as type 2 diabetes. This review of 100 papers aimed to investigate the interconnecting factors which may contribute to poorer prognosis in individuals with covid-19 and type 2 diabetes. Although the evidence suggests that patients with type 2 diabetes have poorer outcomes after contracting covid-19, they are not more susceptible to infection. The paper reported that mechanisms which may increase severity in type 2 diabetics are abnormal immune function, increased susceptibility to inflammation, the increased adherence of the virus to target cells and reduced ability to fight infection. It is important to manage blood sugars when suffering from covid-19. The paper reviewed the use of several medications such as metformin, dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide-1 agonists and insulin in the context of individuals suffering from covid-19, with insulin being the treatment of choice in the acutely ill patient. Current treatments of covid-19 were also reviewed such as chloroquine and hydroxychloroquine, Lopinavir-ritonavir, IL-6 receptor agonists, type 1 interferon and remdesivir. It was concluded that clinicians should be aware of the risks in patients with type 2 diabetes and covid-19. However as new data is made available, the chronic and long-term implications will become clearer. This study could be used by health care professionals to ensure that patients with type 2 diabetes do everything they can to avoid covid-19 infection and that if contracted these patients are closely monitored for severe disease.
Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.
The Long Haul of COVID-19 Recovery: Immune Rejuvenation versus Immune Support.
Integrative medicine (Encinitas, Calif.). 2020;19(6):18-22
Plain language summary
Following Covid-19 infection, sufferers have reported various residual symptoms, which have been likened to those experienced by chronic fatigue sufferers and those with Gulf War syndrome. This review paper aimed to assess whether the body has a similar immune response to these diseases during Covid-19, and if so, what therapies could be used. It also reviewed any diet and lifestyle factors that may be affecting the immune response. The paper stated that Covid-19 infection is associated with inflammation, which can damage immune cells and inflammation prior to Covid-19 infection may contribute to severity of the infection. Prior research in seemingly healthy individuals indicates that environment, diet, and lifestyle factors can all contribute to differing “immune identities” and eliminating immune cells which carry the imprint of memories should be a therapy focus in Covid-19 patients. Fasting, diets low in refined sugars and high in omega-3 and plant chemicals were discussed as ways for the body to clear out immune cells. It was concluded that personalising therapy strategies based on an individual’s immune identity to reduce inflammation could ultimately support the immune system. This paper could be used by healthcare professionals to understand the importance of diet and lifestyle changes to reduce inflammation and support the immune system.
With the COVID-19 pandemic still affecting communities all over the world and "Long Haul" chronic health issues emerging, it is time for us to look back at past multi-symptom health conditions that required a different approach to their treatment, beyond just managing symptoms. It is important for us to consider how to apply what we have learned about immune rejuvenation and its impact on conditions associated with chronic immune dysfunction. We know more than we ever have before about how to reduce chronic inflammation at its source through the support of selective immune cell autophagy/mitophagy and improved immune cell mitochondrial activity, followed by remodeling of the immune epigenome, and-ultimately-a reset of immune function.