What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.

Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.

Diabetes, obesity and COVID-19: A complex interplay.

With the accumulation of observational data showing an association of metabolic co-morbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions which arise from this relationship, and the types of studies needed to answer those questions. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience of or interest in the management of COVID-19.

The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19.

Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. This may be driven by direct endothelial cell entry by the virus, or indirectly by activated inflammatory cascade. Major risk groups identified for adverse outcomes in COVID-19 are diabetes, and those from the Black, Asian and ethnic minority (BAME) populations. Hyperglycaemia (expressed as glycated haemoglobin or mean hospital glucose) correlates with worse outcomes in COVID-19. It is not known whether hyperglycaemia is causative or is a surrogate marker - persistent hyperglycaemia is well known as an aetiological agent in microangiopathy. In this article, we propose that pre-existing endothelial dysfunction of microangiopathy, more commonly evident in diabetes and BAME groups, makes an individual vulnerable to the subsequent 'endothelitis' of COVID-19 infection.