Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and Type-III interferon infectivity restriction

Bronchi of the upper respiratory tract are considered the site of SARSCoV- 2 infection initiation from where a possible spread to the lower respiratory tract can cause acute respiratory distress syndrome with a high degree of mortality in elderly patients. Here we established functional reconstituted primary bronchial epithelia (BE) derived from donors including both adults and children to study SARS-CoV-2 infection dynamics in a physiologically relevant model. We identified multi-ciliated cells as the primary target cells for SARS-CoV-2 in our reconstituted BE. We further observed rapid viral spread throughout the entire BE within 24-48hours. Within 3-4 days, we observed syncytia formation between ciliated cells and basal cells which accumulate at the apical side of the BE. We show that infected cells including syncytia are released into the apical lumen and contribute to the transmittable virus dose. Interestingly, some BE mainly reconstituted from young donor, showed an intrinsic resistance to infection and virus spread. This restricted infection phenotype correlated with a faster release of type-III interferon secretion. Moreover, exogenous type-III interferon treatment to permissive epithelia installed infection restriction while interferon gene knockout promoted infection. Taken together our data uncover syncytia formation as possible contribution to tissue or environmental SARS-CoV-2 dissemination and the type-III IFN response as a central contributor to SARS-CoV-2 resistance in BE, which may explain epidemiological observations that SARS-CoV-2 fatality is age dependent.

Effect of a ketogenic diet vs mediterranean diet on hba1c: The keto-med randomized crossover trial

Background: Growing interest in very low carbohydrate diets, and in particular the ketogenic diet, has been met with some resistance. Important gaps exist regarding what diet to compare to the ketogenic diet. The objective of this study was to compare a Well Formulated Ketogenic Diet (WFKD) with a Mediterranean-Plus diet (Med-Plus;Mediterranean with emphasis on eliminating added sugars and refined grains), in a crossover study, stratified by diabetes status (T2D vs Prediabetes). Methods: The intervention involved having participants follow the WFKD and Med-Plus, for 12 weeks each, in random order. All meals were provided for the first 4 weeks of each diet phase (food delivery);then participants were responsible for purchasing and preparing their own foods (self-provided). The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes included weight, glucose as measured by continuous glucose monitor (CGM), and cardiometabolic risk factors, such as fasting insulin, glucose, and lipids. Results: Among participants randomized (n = 42), 33 had complete data at both diet phases (some missing data attributable to COVID disruptions). Participants were 60 ± 9 (mean ± sd) years of age, 61% men, with BMI 31 ± 5 kg/m2. Adherence for both diets was higher during the food delivery than the self-provided phase, but similar between diets for both phases. HbA1c concentrations were not significantly different between diets, but average CGM glucose levels were significantly lower during the WFKD compared to Med-Plus (p = 0.03). Additionally, WFKD induced a significantly greater decrease in triglycerides (-16% vs -5%, p = 0.02) and greater increase in LDL-C levels (10% vs -5%, p = 0.01), compared to Med-Plus. Weight change on WFKD vs Med-Plus was -8% vs -7% (p = 0.05). Sensitivity analyses largely confirmed the main findings. Conclusions: Participants improved in glucose control and weight management on both diets relative to baseline;however, glucose control was superior on the WFKD. Some caution is warranted when interpreting these results due to pandemic disruptions and a small sample size. A fair comparison of the two diets should also take into consideration non-glycemic effects.

Telemedicine supported strengthening of primary care in WHO South East Asia region: Lessons from the COVID-19 pandemic experiences

The COVID-19 pandemic has exposed the fragmentation of the healthcare delivery systems and highlighted the role of resilient primary healthcare systems for a robust public health response during health emergencies. Primary care while being the first point of contact between the citizens and the health systems has received scant attention or targeted investments over the past several decades. Through this narrative review, we aim to outline the potential role of telehealth in augmenting health systems capacity. While teleconsultations have increased exponentially during the pandemic, evidence suggests that utilisation of primary care for non-emergency and non-COVID-19 conditions such as chronic medical conditions has significantly decreased, suggesting that most telemedicine utilisation has been to address an immediate crisis. In countries with pre-existing national digital health framework and enabling regulatory environments, telehealth interventions while strengthening the public health response to COVID-19 also supported the continuum of care at the primary care level. Even after COVID-19 is controlled, telemedicine has the potential to address persistent obstacles to primary care in the South East Asia region, including scarcity of trained healthcare workers, access challenges and costs associated with in-person care. Telemedicine holds promise in strengthening primary care and has the potential to catalyse achieving universal health coverage.