The underlying mechanisms for severe COVID-19 progression in people with diabetes mellitus: a critical review.

Diabetes mellitus (DM) has a high incidence of comorbidities among patients with severe coronavirus disease 2019 (COVID-19). The elevated prevalence of DM in the world population makes it a significant risk factor because diabetic individuals appear to be prone to clinical complications and have increased mortality rates. Here, we review the possible underlying mechanisms involved in DM that led to worse outcomes in COVID-19. The impacts of hyperglycemia side effects, secondary comorbidities, weakened innate and adaptive immunity, chronic inflammation, and poor nutritional status, commonly present in DM, are discussed. The role of the SARS-CoV-2 receptor and its polymorphic variations on higher binding affinity to facilitate viral uptake in people with DM were also considered. Clinical differences between individuals with type 1 DM and type 2 DM affected by COVID-19 and the potential diabetogenic effect of SARS-CoV-2 infection were addressed.

Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19.

The importance of Zn for human health becomes obvious during Zn deficiency. Even mild insufficiencies of Zn cause alterations in haematopoiesis and immune functions, resulting in a proinflammatory phenotype and a disturbed redox metabolism. Although immune system malfunction has the most obvious effect, the functions of several tissue cell types are disturbed if Zn supply is limiting. Adhesion molecules and tight junction proteins decrease, while cell death increases, generating barrier dysfunction and possibly organ failure. Taken together, Zn deficiency both weakens the resistance of the human body towards pathogens and at the same time increases the danger of an overactive immune response that may cause tissue damage. The case numbers of Corona Virus Disease 19 (COVID-19) are still increasing, which is causing enormous problems for health systems and economies. There is an urgent need to reduce both the number of severe cases and the resulting deaths. While therapeutic options are still under investigation, and first vaccines have been approved, cost-effective ways to reduce the likelihood of or even prevent infection, and the transition from mild symptoms to more serious detrimental disease, are highly desirable. Nutritional supplementation might be an effective option to achieve these aims. In this review, we discuss known Zn deficiency effects in the context of an infection with Severe Acute Respiratory Syndrome-Coronavirus-2 and its currently known pathogenic mechanisms and elaborate on how severe pre-existing Zn deficiency may pre-dispose patients to a severe progression of COVID-19. First published clinical data on the association of Zn homoeostasis with COVID-19 and registered studies in progress are listed.

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis.

During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.