Global Nutrition
Healthcare Council
Guidance for SARS-CoV-2-Induced
Host Metabolic Reprogram (HMR)
Host Metabolic Reprogram (HMR)
MISSION COVID
A global team of leading scientists from food sciences, nutrigenomics, and metabolomics, combine their collective expertise to peer-review the status of evidence-based dietary targets and nutritional strategies to combat the viral-induced host metabolic reprogram (HMR) in SARS-CoV-2 infected and recovered individuals with post-acute sequelae of COVID-19 (PASC) or long-COVID.
COVID
Human ‘severe acute respiratory syndrome coronavirus 2’ (SARS-CoV-2) is a highly transmissible viral pathogen responsible for the ongoing ‘coronavirus disease 2019’ (COVID-19) pandemic. Like other viral pathogens, SARS-CoV-2 lacks its own metabolic machinery; therefore, totally depends on host (human) cellular metabolism for its replication and spread. In SARS-CoV-2 infection, the first and foremost trigger is alteration and re-direction of host bioenergetic resources (mitochondrial ATP pool) to support the neo-synthesis and assembly of viral particles – a biological switch known as the host metabolic reprogram (HMR). The virulence potential of SARS-CoV-2 to invade a wide range of cells and tissues beyond the respiratory system, is manifested into a broad range of clinical syndromes, with varying degrees of severity ranging from asymptomatic, mild, moderate, to severe fatal multi-organ dysfunction syndrome (MODS). The possible risk of a long-term damage to certain affected host organ/systems or the elevated risk of disorders in later life could significantly worsen the burden on global healthcare. Considering the broad diversity of clinical symptoms, varied populations, and underlying comorbidities there is dire necessity for human host-targeted clinical management strategies to combat COVID-19 pandemic. However, the high viral replication rate with inherent genetic mutability, and compact genomic size with lack of metabolic machinery makes SARS-CoV-2 an extremely challenging druggable antiviral target. Nutritional restoration of HMR could provide a potential strategy to combat COVID-19 and its post sequelae. The WHO COVID-19 global statistics as of October 22, 2022:
Million Cases
Million Deaths
Billion Vaccinations
Post-acute sequelae of
COVID-19 (PASC)
PASC, also known as the ‘long COVID’, has emerged as a novel clinical condition in COVID-19 survivors with lingering symptoms (or develop new ones) who fail to return to their baseline health. Based on the duration of persistent clinical manifestations, PASC has been further categorized: i) post-acute COVID with symptoms and abnormalities that persist 4-12 weeks; and ii) chronic COVID with symptoms and abnormalities that persist >12 weeks and not attributable to alternative diagnoses. The PASC pathology is a cumulative outcome of several viral-mediated HMR at cellular level such as: i) SARS-CoV-2 infection-induced tissue damage, ii) hyperinflammation-mediated multiorgan impairment, iii) immune exhaustion/dysregulation, iv) hormonal disturbances from maladaptation of ACE2-related pathways, v) coagulopathies due to endothelial damage/microvascular injury, iv) post-viral autoimmunity, vi) microbial dysbiosis, vii) critical care-associated sequelae or a combination of all above. The burden of individual PASC sequelae vary by demography (age, race, and sex) but consistently higher among patients with existing metabolic syndromes and in survivors from severe acute infection. The five most long-term clinical manifestations of PASC include:
Fatigue
Headache
Brain fog
Hair loss
Dyspnea
COVID-19: A Virus-induced ‘Host Metabolic Reprogram (HMR)’
Viruses hijack the host cellular metabolic machinery to extract adequate energy and carbon skeletons required for their entry and further molecular constructions of viral progeny inside a host cell. The SARS-CoV-2 infection could activate a complex human host-pathogen interactions leading to host metabolic reprogramming (HMR). The HMR could alter mitochondrial function, disrupt glycolysis/tricarboxylic acid (TCA) cycle and affect several metabolic pathways of amino acid, fatty acid, nucleotide, and antioxidant synthesis. Therefore, nutritional restoration of HMR could provide a potential strategy to combat COVID-19/PASC.
The SARS-CoV-2 pathogen relies on host cellular metabolic machinery to acquire specific substrates for their multiplication and propagation. During the infection process, SARS-CoV-2 alters host iron metabolism, reprograms the cellular metabolism to activate several complex host-viral interactions, diminishes mitochondrial function to reduce the levels of TCA cycle metabolites to facilitate the synthesis of amino acids, lipids, and nucleotides required for viral replication. Such SARS-CoV-2-induced HMR in infected host could also affect immune responses, and trigger an array of clinical outcomes, ranging from asymptomatic infections to severe manifestations such as acute respiratory distress syndrome (ARDS), vascular dysfunction, multi-organ failure, and death in COVID-19 cases.
- FeRD & HMR
- Nutrition Research & HMR
- PASC & HMR Monitoring
- Bulletin: Updates/Events
Iron (Fe)-Redox Dysregulation (FeRD) & HMR
The significant role of iron metabolism in HMR onset and altered mitochondrial bioenergetics is evident in the pathobiology of COVID-19. The SARS-CoV-2 pathogen categorically targets the host hematopoietic system and alters the host ‘iron (Fe)-redox homoeostasis (Fe-R-H)’. Accordingly, the tri-phasic clinical progression of COVID-19 include: i) Hypoxia/Hypoxemia, an acute depletion of oxygen (O2) transport in the blood; ii) Hyperferritinemia, an excess presence of iron storage protein, ferritin, in the blood; and iii) Thromboembolism, formation of blood clots with severe obstruction of veins, arteries and circulation. Coagulopathy is a hallmark of iron toxicity and oxidized iron could modulate several pathways of coagulation cascade. Such coagulopathies are characterized by elevated procoagulant factors such as fibrinogen, along with high levels of D-dimers associated with increased case fatality rates. The FeRD could also trigger several clinical manifestations in COVID-19 patients including: i) decrease the functional hemoglobin, ii) increase the cellular iron overload, iii) release free toxic heme into the circulation, iv) manifest hypoxemia and systemic hypoxia, v) reduce nitric oxide synthesis, vi) activate coagulation pathway(s), vii) trigger ferroptosis with oxidative stress and lipoperoxidation, and viii) induce mitochondrial degeneration. Therefore, regulation and maintenance of systemic FeRD is critical for the clinical management of COVID-19. Interestingly, the FeRD and its associated physiological disorders or disease states continue for extended periods (for weeks or even months) in COVID-19 patients discharged as RT-PCR (SARS-CoV-2) negative survivors. Based on these virus-independent clinical manifestations and the intrinsic pathophysiological imbalance of host ‘redox homeostasis’, PASC should be considered as a ‘FeRD Syndrome’. Accordingly, the restoration of host Fe-R-H and recalibration of viral-induced HMR could help in the development of novel clinical biomarkers to monitor the nutritional state of an affected individual and identify potential cellular metabolic targets for healthy recovery of patients.
Nutrition Research & HMR
Metabolic status, in particular, the diet, nutrition, age, sex, medical condition(s), lifestyle, and environmental factors, cumulatively govern the clinical manifestation and disease outcomes of COVID and PASC. Both FeRD and HMR in tandem, with altered mitochondrial function (cellular bioenergetics) are decisive factors in the symptomatic onset and progressive clinical phases of both COVID-19 and PASC. The FeRD and HMR triggered physiological disorders or disease states could remain for extended periods (for weeks or even months) in PASC affected individuals, i.e., COVID-19 patients discharged as RT-PCR (SARS-CoV-2) negative survivors. These observations strongly emphasize the therapeutic and prophylactic potential for FeRD restorative nutritional/metabolic strategies in the global management of COVID and PASC. The pathobiology of COVID-19 could negatively impact the metabolic parameters of a patient at different levels such as: i) by increasing specific nutritional demand as a consequence of pyrexia, sepsis, dyspnea, and/or ii) by reducing dietary intake due to excessive coughing, dysphagia, dysgeusia, chronic fatigue, poor appetite and food access issues. Therefore, nutritional strategies or recommendations should consider both the viral-specific virulence targets (i.e., viral entry blockers and viral replication inhibitors), as well as specific host defense factors (i.e., anti-inflammatories, immune modulators, antioxidants, and metabolic optimizers) for obtaining effective outcomes. Nutrition is considered an ultimate effector for both adaptation and operation of the human gene, metabolism, and optimal health; accordingly, the traditional philosophy of ‘Food as Medicine’, sets the foundation for nutrition-based healthcare! The prime goal of Mission COVID is to provide peer-reviewed scientific data and expert opinions to both global research community as well as public-at-large about the ongoing developments and emerging intervention technologies in the field of nutrition/food science for global control of COVID-19/PASC. Mission COVID will collaborate with leading laboratories worldwide to conduct nutrition research in the following areas antiviral research:
- Evaluating in vivo efficacy for bio-redox nutrients to combat FeRD. These include innate Fe-redox regulators (i.e., milk lactoferrin, hemeoxygenase-1, erythropoietin (EPO), and hepcidin modulators); ferroptosis inhibitors; anticoagulants (i.e., heparin); and natural phytochemical iron-chelators.
- Develop bioactive nutrients to restore mitochondrial function and cell membrane protease activity. These include ACE2 and neuropilin-2 (Nrp2) modulators and regulators of furin, TMPRSS2, cathepsin L activity
- Design total health recovery strategies for PASC with system-targeted personalized nutrition
- Novel REDOX Interventions such as: electrolyzed water (aqua-redox), proton-activated lipid matrices – PALM (omega-redox), etc.
PASC & HMR Monitoring
PASC is characterized by malnutrition, loss of fat-free body mass, and low-grade inflammation. The recovery of these patients might be complicated by persistent symptoms such as functional impairment (i.e., fatigue and sarcopenia), dysphagia (particularly among intubated patients), loss of appetite, and taste/smell alterations (ageusia/anosmia). Therefore, any nutritional strategies for PASC management should address to rectify dietary deficiencies for adequate recovery of physical and functional wellbeing, as well as mental health of patients. The primary goal of such protocol is to prevent complications and support recovery to enable COVID-19 and PASC patients to achieve the best possible physical, functional, and mental health status. Both in COVID-19 survivors and chronic PASC patients, monitoring of HMR perturbations in the FeRD-related biochemical pathways is an innovative approach. The intricate impairments and sequelae are associated with eight major physiological systems in COVID-19 survivors (i.e., pulmonary, neuro-cognitive, cardiovascular, renal, gastrointestinal/hepato-biliary, endocrinal, skeleton-muscular, and reproductive) – triggered by the FeRD, amplified by the HMR, altered mitochondrial function and ACE2/RAAS axis. Finally, the evaluation of nutritional status and HMR monitoring should be mandatory for all COVID-19 and PASC patients. Such evaluation should be conducted at every stage of the clinical manifestation and recovery of COVID-19. Also, most patients experience weight reduction during COVID-19 infection, due to increased inflammation, appetite loss linked to anosmia/ageusia. Therefore, it is critical to correct the imbalance between energy expenditure and dietary (calorie) intake of such patients. The monitoring of nutritional status is of prime importance in the clinical management of hospitalized COVID-19 patients and in the rehabilitation of PASC individuals. Specific biomarker assays should be developed to measure metabolomic alterations in bioenergetic pathway intermediates, lipids, antioxidants, and amines, which could prove highly beneficial to identify molecular phenotypes among PASC patients. Such metabolomic analysis could also help in establishing dietary requirements for personalized nutrition, as well as in developing target-specific food bioactives for PASC management.
- Nutrigenomic Responses
- Restore Mitochondrial Activity
- Restore Cognitive Function
- Optimize Cellular Metabolism
- Optimize Reproductive/Fertility parameters
Bulletin: Updates/Events
COVID-19, the ongoing global health crisis direly needs an extensive evaluation of potential prophylactic and therapeutic protocols for an effective management of this viral pandemic and its aftermath – the PASC. Due to the unprecedented nature of the COVID-19 pandemic in severity and scale, many countries have been overwhelmed by economic challenges and healthcare demands, especially in implementing the nutritional protocols. Several technological gaps have been noticed in dietary management of COVID-19 survivors, which intensified the emergence of ‘new onset’ metabolic syndromes, especially in low and middle-income countries. Now is the time to identify, collect, store, manage, and provide reliable evidence-based scientific data to foster innovations in nutrition and food science, and help steer the global research as well as the public health/regulatory agencies for an effective combat against COVID-19 and PASC. Mission COVID is committed to organize several national and international events with a dedicated consortium of scientists from all six continents. Our effort to bring evidence-based scientific data, technological innovations, will be showcased as the following:
- Symposia & Conferences
- Webinars & Workshops
- Publications & Reviews
- Expert Opinion & Film Journal
MISSION COVIDDirector-General
“I welcome you to join Mission COVID - our global effort to combat COVID-19 and PASC based on evidence-based scientific innovations in nutrition and human metabolism."
Dr. A S ‘Narain’ Naidu
MISSION COVIDDirector-General
“I welcome you to join Mission COVID - our global effort to combat COVID-19 and PASC based on evidence-based scientific innovations in nutrition and human metabolism."
Dr. AS ‘Narain’ Naidu
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