COVID-19 and metabolic disease: mechanisms and clinical management.

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

Spatially resolved qualified sewage spot sampling to track SARS-CoV-2 dynamics in Munich - One year of experience.

Wastewater-based epidemiology (WBE) is a tool now increasingly proposed to monitor the SARS-CoV-2 burden in populations without the need for individual mass testing. It is especially interesting in metropolitan areas where spread can be very fast, and proper sewage systems are available for sampling with short flow times and thus little decay of the virus. We started in March 2020 to set up a once-a-week qualified spot sampling protocol in six different locations in Munich carefully chosen to contain primarily wastewater of permanent residential areas, rather than industry or hospitals. We used RT-PCR and sequencing to track the spread of SARS-CoV-2 in the Munich population with temporo-spatial resolution. The study became fully operational in mid-April 2020 and has been tracking SARS-CoV-2 RNA load weekly for one year. Sequencing of the isolated viral RNA was performed to obtain information about the presence and abundance of variants of concern in the Munich area over time. We demonstrate that the evolution of SARS-CoV-2 RNA loads (between <7.5 and 3874/ml) in these different areas within Munich correlates well with official seven day incidence notification data (between 0.0 and 327 per 100,000) obtained from the authorities within the respective region. Wastewater viral loads predicted the dynamic of SARS-CoV-2 local incidence about 3 weeks in advance of data based on respiratory swab analyses. Aligning with multiple different point-mutations characteristic for certain variants of concern, we could demonstrate the gradual increase of variant of concern B.1.1.7 in the Munich population beginning in January 2021, weeks before it became apparent in sequencing results of swabs samples taken from patients living in Munich. Overall, the study highlights the potential of WBE to monitor the SARS-CoV-2 pandemic, including the introduction of variants of concern in a local population.

Diabetes Care During COVID-19 Pandemic in Singapore Using a Telehealth Strategy.

Singapore currently has one of highest number of confirmed COVID-19 cases in Southeast Asia. To curb the further spread of COVID-19, Singapore government announced a temporary nationwide lockdown (circuit breaker). In view of restrictions of patients' mobility and the enforcement of safe distancing measures, usual in-person visits were discouraged. Here we describe how diabetes care delivery was ad hoc redesigned applying a telehealth strategy. We describe a retrospective assessment of subjects with diabetes, with and without COVID-19 infection, during the circuit breaker period of 7th April to 1st June 2020 managed through Tan Tock Seng Hospital's telehealth platform. The virtual health applications consisted of telephone consultations, video telehealth visits via smartphones, and remote patient monitoring. The TTSH team intensively managed 298 diabetes patients using a telehealth strategy. The group comprised of (1) 84 inpatient COVID-19 patients with diabetes who received virtual diabetes education and blood glucose management during their hospitalisation and follow-up via phone calls after discharge and (2) 214 (n=192 non-COVID; n=22 COVID-positive) outpatient subjects with suboptimal glycaemic control who received intensive diabetes care through telehealth approaches. Remote continuous glucose monitoring was applied in 80 patients to facilitate treatment adjustment and hypoglycaemia prevention. The COVID-19 pandemic situation mooted an immediate disruptive transformation of healthcare processes. Virtual health applications were found to be safe, effective and efficient to replace current in-person visits.

The ACE-2 in COVID-19: Foe or Friend?

COVID-19 is a rapidly spreading outbreak globally. Emerging evidence demonstrates that older individuals and people with underlying metabolic conditions of diabetes mellitus, hypertension, and hyperlipidemia are at higher risk of morbidity and mortality. The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT1R axis and ACE-2-Ang-(1-7)-Mas axis. In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT1R axis with a downregulation of ACE-2-Ang-(1-7)-Mas axis. The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. On the other hand, the ACE-2-Ang-(1-7)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. In effect, the balance between these two axes may determine the prognosis. The already strained ACE-2-Ang-(1-7)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19.

Practical recommendations for the management of diabetes in patients with COVID-19.

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.