Network spreading among areas: A dynamical complex network modeling approach.

With the outbreak of COVID-19, great loss and damage were brought to human society, making the study of epidemic spreading become a significant topic nowadays. To analyze the spread of infectious diseases among different areas, e.g., communities, cities, or countries, we construct a network, based on the epidemic model and the network coupling, whose nodes denote areas, and edges represent population migrations between two areas. Each node follows its dynamic, which describes an epidemic spreading among individuals in an area, and the node also interacts with other nodes, which indicates the spreading among different areas. By giving mathematical proof, we deduce that our model has a stable solution despite the network structure. We propose the peak infected ratio (PIR) as a property of infectious diseases in a certain area, which is not independent of the network structure. We find that increasing the population mobility or the disease infectiousness both cause higher peak infected population all over different by simulation. Furthermore, we apply our model to real-world data on COVID-19 and after properly adjusting the parameters of our model, the distribution of the peak infection ratio in different areas can be well fitted.

A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.

Investigating the risks of removing wild meat from global food systems.

The COVID-19 pandemic has brought humanity's strained relationship with nature into sharp focus, with calls for cessation of wild meat trade and consumption, to protect public health and biodiversity.1,2 However, the importance of wild meat for human nutrition, and its tele-couplings to other food production systems, mean that the complete removal of wild meat from diets and markets would represent a shock to global food systems.3-6 The negative consequences of this shock deserve consideration in policy responses to COVID-19. We demonstrate that the sudden policy-induced loss of wild meat from food systems could have negative consequences for people and nature. Loss of wild meat from diets could lead to food insecurity, due to reduced protein and nutrition, and/or drive land-use change to replace lost nutrients with animal agriculture, which could increase biodiversity loss and emerging infectious disease risk. We estimate the magnitude of these consequences for 83 countries, and qualitatively explore how prohibitions might play out in 10 case study places. Results indicate that risks are greatest for food-insecure developing nations, where feasible, sustainable, and socially desirable wild meat alternatives are limited. Some developed nations would also face shocks, and while high-capacity food systems could more easily adapt, certain places and people would be disproportionately impacted. We urge decision-makers to consider potential unintended consequences of policy-induced shocks amidst COVID-19; and take holistic approach to wildlife trade interventions, which acknowledge the interconnectivity of global food systems and nature, and include safeguards for vulnerable people.