Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge.

The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity.

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

Key Aspects in Nutritional Management of COVID-19 Patients.

This review deals with the relationship among nutrition, the immune system, and coronavirus disease 2019 (COVID-19). The influence of nutrients and bioactive molecules present in foodstuffs on immune system activity, the influence of COVID-19 on the nutritional status of the patients, and the dietary recommendations for hospitalized patients are addressed. Deficient nutritional status is probably due to anorexia, nausea, vomiting, diarrhea, hypoalbuminemia, hypermetabolism, and excessive nitrogen loss. There is limited knowledge regarding the nutritional support during hospital stay of COVID-19 patients. However, nutritional therapy appears as first-line treatment and should be implemented into standard practice. Optimal intake of all nutrients, mainly those playing crucial roles in immune system, should be assured through a diverse and well-balanced diet. Nevertheless, in order to reduce the risk and consequences of infections, the intakes for some micronutrients may exceed the recommended dietary allowances since infections and other stressors can reduce micronutrient status. In the case of critically ill patients, recently published guidelines are available for their nutritional management. Further, several natural bioactive compounds interact with the angiotensin-converting enzyme 2 (ACE2) receptor, the gateway for severe acute respiratory syndrome (SARS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Natural bioactive compounds can also reduce the inflammatory response induced by SARS-CoV-2. These compounds are potential beneficial tools in the nutritional management of COVID-19 patients.