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Sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for type 2 diabetes: a narrative review with emphasis on data from Europe.
Kyrou, I, Tsigos, C, Mavrogianni, C, Cardon, G, Van Stappen, V, Latomme, J, Kivelä, J, Wikström, K, Tsochev, K, Nanasi, A, et al
BMC endocrine disorders. 2020;20(Suppl 1):134
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Type 2 diabetes mellitus (T2DM) results from progressive loss of insulin secretion, which is typically combined with various degrees of insulin resistance. The aim of this study is to provide a comprehensive overview of key sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for T2DM with emphasis on data from Europe. This study is a narrative review which includes 101 publications. Literature shows that prevention of T2DM should be a collaborative effort which mobilizes multiple partners/ stakeholders at a national and international (e.g. European) level. In addition, a holistic approach is becoming increasingly essential in order to put into effect multidimensional public health programs and integrated interventions for effective T2DM prevention which will take into account both traditional and socioeconomic/socioecological factors. Authors conclude that a multidimensional approach for the prevention of T2DM may have a broader impact against the current diabesity epidemic within and across countries in Europe.
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare burden of diabetes is noted in Europe, where 8.8% of the population aged 20-79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions. METHODS For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000. RESULTS Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors. CONCLUSION In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.
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Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults: From Whole-Foods to Isolated Ingredients.
Marshall, RN, Smeuninx, B, Morgan, PT, Breen, L
Nutrients. 2020;12(5)
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Human skeletal muscle mass and strength are significant for maintaining cardio-metabolic health and locomotion in older age. With advancing age, a loss of muscle mass and strength is observed (sarcopenia), increasing the risk of falls, fractures, and mortality. The aim of this review was to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals. Literature shows that: To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. Optimising nutritional intake via high-quality proteins, food-fortification and/or oral nutritional supplements could potentially attenuate disuse-induced impairments in muscle protein turnover that drive the atrophy process. Targeted single and/or multi-ingredient supplements may facilitate accrual and retention of muscle tissue during disuse events and may be a preferable strategy in older adults who are unable to consume adequate high-quality dietary protein from whole-foods alone. Authors conclude that further research is needed to determine the temporal change in muscle protein turnover during disuse events and translate promising evidence of potentially beneficial nutritional supplements/ingredients into a clinically relevant setting.
Abstract
Preserving skeletal muscle mass and functional capacity is essential for healthy ageing. Transient periods of disuse and/or inactivity in combination with sub-optimal dietary intake have been shown to accelerate the age-related loss of muscle mass and strength, predisposing to disability and metabolic disease. Mechanisms underlying disuse and/or inactivity-related muscle deterioration in the older adults, whilst multifaceted, ultimately manifest in an imbalance between rates of muscle protein synthesis and breakdown, resulting in net muscle loss. To date, the most potent intervention to mitigate disuse-induced muscle deterioration is mechanical loading in the form of resistance exercise. However, the feasibility of older individuals performing resistance exercise during disuse and inactivity has been questioned, particularly as illness and injury may affect adherence and safety, as well as accessibility to appropriate equipment and physical therapists. Therefore, optimising nutritional intake during disuse events, through the introduction of protein-rich whole-foods, isolated proteins and nutrient compounds with purported pro-anabolic and anti-catabolic properties could offset impairments in muscle protein turnover and, ultimately, the degree of muscle atrophy and recovery upon re-ambulation. The current review therefore aims to provide an overview of nutritional countermeasures to disuse atrophy and anabolic resistance in older individuals.
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COVID-19: Exposing and addressing health disparities among ethnic minorities and migrants.
Greenaway, C, Hargreaves, S, Barkati, S, Coyle, CM, Gobbi, F, Veizis, A, Douglas, P
Journal of travel medicine. 2020;27(7)
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The coronavirus disease 2019 (COVID-19) has swept across the world affecting all countries. As COVID-19 has spread within countries, vulnerable and marginalized populations, and those with low income and low socioeconomic status have been unduly affected. Every country has vulnerable populations that require special attention from policy makers in their response to the current pandemic. In fact, current literature shows that migrants living in refugee camps, detention centres and reception centres are at particularly high risk for COVID-19 exposure. Therefore, they should be included in national surveillance and be entitled to health care. In addition, it is essential to foster trust between public health practitioners and the leadership of these communities so that they may work together to effectively deliver prevention and intervention strategies. Authors conclude that COVID-19 pandemic has exposed health disparities among ethnic minorities and certain migrant groups. Thus, they highlight the importance of prompting greater health equity for diverse ethnocultural communities.
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COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities.
Abuelgasim, E, Saw, LJ, Shirke, M, Zeinah, M, Harky, A
Current problems in cardiology. 2020;45(8):100621
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The 2019 coronavirus disease (COVID-19), is a public health emergency with serious adverse implications for populations, healthcare systems, and economies globally. The aim of this review was to explore the possible association between ethnicity, incidence and outcomes of COVID-19 using both recent COVID-19 studies and studies of previous pandemics. Findings show that: - ethnic minorities have lower lung function compared to their Caucasian counterparts. - Black, Asian and Minority Ethnics communities are prone to higher rates of cardiovascular disease and are subject to adverse healthcare disparities. - ethnic minorities are disproportionately affected, and experience worse health outcomes compared to other groups. They are also more likely to be socioeconomically disadvantaged compared to white communities. - Africans are at a higher risk of receiving later and more indigent healthcare compared to other ethnic groups. Authors conclude that data on ethnicity should be routinely collected by governments to robustly determine magnitude of association. In addition, governments should also recommend strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.
Abstract
The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of an international collaboration, alongside other patient demographics and further research to robustly determine the magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.
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Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.
Al-Horani, RA, Kar, S
Viruses. 2020;12(10)
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The covid-19 pandemic has required the identification of therapies to prevent infection and limit severity. A previous paper by the same authors reviewed therapies that block the virus in the early stages of its lifecycle. This very large review of over 300 papers aimed to summarise therapeutics which are aimed at blocking the lifecycle of the virus after it has entered the body’s cells. The authors began by reviewing the lifecycle of the covid-19 virus explaining how it enters the body’s cells, replicates inside and then is released to infect new cells. Several antivirals, antimalarials and natural products were then reviewed. Of note, Remdesivir is being trialled in covid-19 patients, with mixed results, however, is being recommended in the US for the treatment of hospitalised covid-19 patients with severe disease. Ribavirin, which is being trialled in combination with other antivirals is also showing promising results in shortening hospitalisation times in covid-19 patients. It was concluded that any stage of the covid-19 lifecycle could be a target for therapeutics and combining therapies is likely to be more successful than monotherapy. This paper could be used by health care professionals to understand the most recent therapeutic research for covid-19.
Abstract
The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.
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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.
Khadke, S, Ahmed, N, Ahmed, N, Ratts, R, Raju, S, Gallogly, M, de Lima, M, Sohail, MR
Virology journal. 2020;17(1):154
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Severe manifestations of COVID-19 infection and mortality are associated with a cytokine storm. This is an excessive inflammatory response to the infection leading to an overproduction of pro-inflammatory signalling molecules, which consequently contributes to tissue and organ damage. This literature review summarised current knowledge, as of June 2020, about virus-associated cytokine storm, virus-host interactions and immunological mechanism, to gain a better understanding of the phenomena observed in COVID-19 infections and devise better treatment strategies. The review briefly outlines the epidemiology of COVID-19, predictors of severity of disease, mode of transmission, testing, viral structure, mechanism of invasion of the host cell, replication and immune invasion and the progression of the four stages of the cytokine storm. The second part of the review discusses antiviral therapeutics of interest with a table summarising drugs, mechanism and available data. This article may be of interest to those who like to delve further into the mechanisms and immune components involved in a cytokine storm and gain an oversight of the pathways targeted by allopathic agents that have been put forward as treatment options.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
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Dissecting the interaction between COVID-19 and diabetes mellitus.
Chee, YJ, Tan, SK, Yeoh, E
Journal of diabetes investigation. 2020;11(5):1104-1114
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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.
Abstract
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.
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Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?
Menegazzi, M, Campagnari, R, Bertoldi, M, Crupi, R, Di Paola, R, Cuzzocrea, S
International journal of molecular sciences. 2020;21(14)
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Some individuals who have contracted Covid-19 experience an extreme inflammatory reaction known as cytokine storm syndrome. This review paper of 129 studies aimed to review the use of epigallocatechin 3-gallate (EGCG), a green tea derived chemical reported to reduce inflammation with a view to be used in individuals with Covid-19. Conventional therapies used in diseases known to induce extreme inflammation were discussed focusing on steroid based drugs. However, results in Covid-19 patients have shown increased mortality and decreased viral clearance. Several other drugs are being trialled in Covid-19. The use of EGCG and green tea extract (GTE) in several diseases such as rheumatoid arthritis, Sjogrens syndrome, multiple sclerosis, human immunodeficiency virus, dengue virus and inflammatory bowel disease was discussed and beneficial effects such as being anti-inflammatory, antiviral, antimicrobial, and having anti-cancer properties were outlined. The possible mechanisms involved were extensively discussed. The use of EGCG and GTE in a clinical setting was reported to have favourable outcomes and be a potentially safe natural supplement. It was concluded that given the safety and many benefits shown by EGCG in viruses and inflammatory diseases, EGCG/GTE may be effective in Covid-19, and clinical trials are needed. This study could be used by healthcare professionals to justify the recommendation of EGCG/GTE in individuals with Covid-19 and many other inflammatory and viral diseases.
Abstract
Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
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Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?
Giovinazzo, G, Gerardi, C, Uberti-Foppa, C, Lopalco, L
Molecules (Basel, Switzerland). 2020;25(24)
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During covid-19 infection the body experiences a hyper-immune reaction resulting in an extreme inflammatory response known as cytokine release syndrome (CRS), which correlates with poor prognosis and severe illness. There are no effective treatments for CRS, although there are ongoing trials. The use of natural plant chemicals known as polyphenols have been shown in previous trials to improve inflammation This review of over 90 studies aimed to summarise the use of polyphenols to fight severe covid-19 infection. The paper began by reviewing current drug therapies, which have been shown in studies to be of benefit to inflammation, with tocilizumab being heavily reviewed. The authors then reviewed several plant polyphenols and reviewed how they can modulate inflammation through inhibiting inflammatory molecules and viral activity. It was concluded that human studies are lacking data and so phytochemicals may be promising for the treatment of covid-19. This study could be used by health care professionals to understand the importance of recommending a whole food, plant rich diet with many different coloured foods for individuals who are suffering from covid-19.
Abstract
SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.
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Melatonin: Roles in influenza, Covid-19, and other viral infections.
Anderson, G, Reiter, RJ
Reviews in medical virology. 2020;30(3):e2109
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Viruses like influenza and coronaviruses change quickly, making it challenging to develop effective treatments and vaccines in a short time frame. Consequently, the use of generic substances that limit viral effects are of high interest. In this paper, the authors summarize a range of mechanisms in which melatonin can alter the impact of virus infections and infection-associated inflammatory overdrive aka cytokine storm. Melatonin, the sleep hormone, is well known for its potent antioxidant and anti-inflammatory action. It seems highly likely that melatonin can modulate the cellular function of all cells, mostly via mitochondrial function. This is particularly relevant in immune cells. For example, the daytime variance in immune function seems to be closely linked with mitochondrial activity and energy production. Other relevant mechanisms described are the antiviral role of melatonin-induced sirtuins - proteins that regulate cellular health-, the impact of viruses on cell coordinating microRNA, the role of the gut microbiome and gut permeability, as well as sympathetic nervous system activation and the protective effects of parasympathetic activation. Also considered are pre-existing health conditions and conditions that are linked with a decline in melatonin along with ageing, all being groups in which severity of viral infections is felt. This paper may be of interest to those who like to explore in more depth the mechanisms behind melatonin and its ability to influence viral disease progression.
Abstract
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus- and cytokine-storm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.