There may be interactions between obesity, diet and COVID-19, possibly linked with Nrf2. Obesity is a very important risk factor for COVID-19 severity and is often associated with diet. They may also interact with SARS-CoV-2 by other pathways involved in IR that may be Nrf2-dependent or -independent. They may be important in the mitigation of COVID-19, acting through the endoplasmic reticulum (ER) or ACE-Angiotensin-II-AT 1R axis (AT 1R) pathway and leading to insulin resistance (IR), endothelial damage, lung injury and cytokine storm. berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) and lactobacilli acting as antioxidants are effective against insulin resistance associated diseases. Several Nrf2-interacting natural compounds (e.g. It expresses a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 is a pleiotropic transcription factor protecting against oxidative stress.
Reactive oxygen species (ROS) exert beneficial and toxic effects on cellular functions. Notwithstanding the fact that data from ecological studies need to be interpreted with caution, fermented vegetables or cabbage have been found to be associated with low COVID-19 death rates in European countries. Some very low death rate settings (but not Australia or New Zealand) have a common feature of eating large quantities of fermented vegetables such as cabbage, other members of the Brassicaceae family and, in some continents, various spices. This geographical pattern is very unlikely to be totally due to reporting differences between countries. Although there are many pitfalls in analyzing death rates for COVID-19, death rates were low or very low in Central European countries, Eastern Asian countries, many Sub-Saharan African countries, the Middle East, India and Pakistan as well as Australia and New Zealand. Diet represents only one of the possible causes of the COVID-19 epidemic. The COVID-19 epidemic is multifactorial, and factors like climate, population density, social distancing, age, phenotype, obesity and prevalence of non-communicable diseases are associated to increased incidence and mortality. Like most diseases, COVID-19 exhibits large geographical variations which frequently remain unexplained. Large differences in COVID-19 death rates exist between countries and regions of the same country. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT 1R axis (AT 1R) pathway. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are large between- and within-country variations in COVID-19 death rates.