Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

Effect of probiotic intervention on intestinal flora and immune status in patients with secondary infections to HBV-related acute-on-chronic liver failure

Objective To assess the effect of probiotic intervention on intestinal flora and immune status in patients with secondary infections to HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 101 patients with HBV-ACLF treated in our hospital between January, 2017 and June, 2018 were enrolled in this study, including 56 without secondary infections (HBV-ACLF group) and 45 with secondary infections to HBV-ACLF (secondary infection group), with 67 healthy participants as controls. All the patients with HBV-ACLF were treated with bifidobacterium quadruple live bacteria tablets in addition to the routine treatments for 1 month. From all the participants, fecal specimens were collected before and after the treatment to analyze the changes in Lactobacillus, Bifidobacterium, Escherichia coli, Enterococcus, yeast, Staphylococcus, Bacteroides and Streptococcus mutans; peripheral blood samples were also obtained for testing the serum levels of immunoglobulin A (IgA), IgG and IgM using ELISA; the changes in T lymphocyte subsets CD3+, CD4+ and CD8+ were detected using immunofluorescence flow cytometry, and the levels of C-reactive protein (CRP), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-8(IL-8) were determined using ELISA. Results Compared with the control group, the patients with HBV-ACLF in both groups before the treatment showed significantly reduced abundance of intestinal Lactobacilli and Bifidobacteria and increased abundance of Escherichia coli, Enterococcus, yeast, Staphylococcus, Bacteroides, and Streptococcus pneumoniae (P 0.05). Conclusion The patients with secondary infections to HBV-ACLF have abnormal changes in intestinal flora and immune status, which can be improved by probiotic intervention

Low-Cost and Scalable Platform with Multiplexed Microwell Array Biochip for Rapid Diagnosis of COVID-19

Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens

Summary report of systematic reviews for public health emergency operations centres. Plans and procedures; communication technology and infrastructure; minimum datasets and standards; training and exercises.

A public health emergency operations centre (PHEOC) exists to coordinate information and resources in order to manage responses to public health events or emergencies. Emergency operations centres (EOCs) are used in a variety of emergencies, including natural disasters; foodborne disease outbreaks; radio-nuclear events; bioterrorism; chemical incidents; mass gatherings; blackouts; humanitarian emergencies; and disease outbreaks or pandemics. They are employed at a variety of jurisdictional levels, and range from field EOCs to local, regional, national or international EOCs. Effective communication and coordination within and between EOCs and response agencies is critical to the successful management of an emergency. The structure and function of EOCs varies across countries and organisations; they have different capacities and resources, and use different staff, terminologies, procedures and tools. These variations pose significant challenges to the interoperability that is essential to effective coordination between EOCs and responding agencies. In 2012, WHO's Department of Global Capacities, Alert and Response (GCR) established the Public Health Emergency Operations Centre Network (EOC-NET)[2]. EOC-NET exists to support Member States as they strengthen their capacity for effective response to public health emergencies, in line with the requirements of the 2005 International Health Regulations. EOC-NET has four working groups focussed on priority areas in public health emergency response: 1. The EOC Communication Technology and Infrastructure (CTI) working group, which provides guidance on minimum CTI requirements and assessment tools. 2. The EOC Minimum Data Sets and Standards (MDSS) working group, which develops guidance on minimum datasets, data structure, standards and common terminologies to ensure interoperability, effective data collection, display and exchange of operational information. 3. The EOC Procedures and Plans (P&P) working group, which identifies or develops generic procedures and plans, and standard operating procedures (SOPs). 4. The EOC Training and Exercises (T&E) working group, which develops training programmes and exercises for EOC personnel. In December 2013, WHO conducted a systematic review of public health emergency operations centres[3], in collaboration with Emory University. This review documented best practices and barriers in establishing and using EOCs for effective responses to public health emergencies. This review has been followed by four more focussed reviews exploring key elements of EOCs: communication technology and infrastructure, minimum datasets and standards, plans and procedures, and training and exercises. The results of all five reviews will be used to inform the development of a series of guidance resources and recommendations for PHEOCs. This report summarises the four focussed reviews