A CRISPR-based ultrasensitive assay detects attomolar concentrations of SARS-CoV-2 antibodies in clinical samples.

CRISPR diagnostics are powerful tools for detecting nucleic acids but are generally not deployable for the detection of clinically important proteins. Here, we report an ultrasensitive CRISPR-based antibody detection (UCAD) assay that translates the detection of anti-SARS-CoV-2 antibodies into CRISPR-based nucleic acid detection in a homogeneous solution and is 10,000 times more sensitive than the classic immunoassays. Clinical validation using serum samples collected from the general population (n = 197), demonstrates that UCAD has 100% sensitivity and 98.5% specificity. With ultrahigh sensitivity, UCAD enables the quantitative analysis of serum anti-SARS-CoV-2 levels in vaccinated kidney transplant recipients who are shown to produce "undetectable" anti-SARS-CoV-2 using standard immunoassay. Because of the high sensitivity and simplicity, we anticipate that, upon further clinical validation against large cohorts of clinical samples, UCAD will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.

Immune Response Is Key to Genetic Mechanisms of SARS-CoV-2 Infection With Psychiatric Disorders Based on Differential Gene Expression Pattern Analysis.

Existing evidence demonstrates that coronavirus disease 2019 (COVID-19) leads to psychiatric illness, despite its main clinical manifestations affecting the respiratory system. People with mental disorders are more susceptible to COVID-19 than individuals without coexisting mental health disorders, with significantly higher rates of severe illness and mortality in this population. The incidence of new psychiatric diagnoses after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also remarkably high. SARS-CoV-2 has been reported to use angiotensin-converting enzyme-2 (ACE2) as a receptor for infecting susceptible cells and is expressed in various tissues, including brain tissue. Thus, there is an urgent need to investigate the mechanism linking psychiatric disorders to COVID-19. Using a data set of peripheral blood cells from patients with COVID-19, we compared this to data sets of whole blood collected from patients with psychiatric disorders and used bioinformatics and systems biology approaches to identify genetic links. We found a large number of overlapping immune-related genes between patients infected with SARS-CoV-2 and differentially expressed genes of bipolar disorder (BD), schizophrenia (SZ), and late-onset major depressive disorder (LOD). Many pathways closely related to inflammatory responses, such as MAPK, PPAR, and TGF-ß signaling pathways, were observed by enrichment analysis of common differentially expressed genes (DEGs). We also performed a comprehensive analysis of protein-protein interaction network and gene regulation networks. Chemical-protein interaction networks and drug prediction were used to screen potential pharmacologic therapies. We hope that by elucidating the relationship between the pathogenetic processes and genetic mechanisms of infection with SARS-CoV-2 with psychiatric disorders, it will lead to innovative strategies for future research and treatment of psychiatric disorders linked to COVID-19.

The CRISPR-Cas toolbox for analytical and diagnostic assay development.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) systems have revolutionized biological and biomedical sciences in many ways. The last few years have also seen tremendous interest in deploying the CRISPR-Cas toolbox for analytical and diagnostic assay development because CRISPR-Cas is one of the most powerful classes of molecular machineries for the recognition and manipulation of nucleic acids. In the short period of development, many CRISPR-enabled assays have already established critical roles in clinical diagnostics, biosensing, and bioimaging. We describe in this review the recent advances and design principles of CRISPR mediated analytical tools with an emphasis on the functional roles of CRISPR-Cas machineries as highly efficient binders and molecular scissors. We highlight the diverse engineering approaches for molecularly modifying CRISPR-Cas machineries and for devising better readout platforms. We discuss the potential roles of these new approaches and platforms in enhancing assay sensitivity, specificity, multiplexity, and clinical outcomes. By illustrating the biochemical and analytical processes, we hope this review will help guide the best use of the CRISPR-Cas toolbox in detecting, quantifying and imaging biologically and clinically important molecules and inspire new ideas, technological advances and engineering strategies for addressing real-world challenges such as the on-going COVID-19 pandemic.

Epidemic situation and control measures of African Swine Fever Outbreaks in China 2018-2020.

As of 21 April 2020, 176 ASF outbreaks have occurred in China. For each outbreak, an investigation was conducted, including historical data retrieval and traceability of potential contacts. The purpose of this study is to conduct a preliminary analysis of the data obtained from the outbreak investigations, including an investigation of the possible contributing factors of the spread of ASF in China. Based on the epidemic situation and the policies issued, the entire epidemic can be divided into three phases. 71 outbreaks were reported between 3 August 2018 and 17 November 2018; 44 outbreaks between 19 November 2018 and 30 March 2019; and 61 outbreaks between 4 April 2019 and 12 April 2020. Based on the reported outbreaks, the proportional rate of outbreaks in small farms (livestock ≤ 500, 127/168) is significantly higher than that of medium (501 ≤ livestock < 2,000, 14/168; 2001 ≤ livestock ≤ 5,000, 9/168) and large farms (livestock ≥ 5,001, 18/168). The odds of infection related to swill feeding (OR = 2.5, 95% CI, 1.5-4.3) and the mechanical dissemination of vehicles and personnel (OR = 2.7, 95% CI, 1.6-4.5) are significantly higher than those of pigs and pig production transportation. Swill feeding is the major contributing factor for small farms while mechanical dissemination of vehicles and personnel is the major contributing factor for large farms. The average duration from the beginning of the infection to the official outbreak report is gradually decreasing, which means that response speed of industry entities and the animal husbandry and veterinary departments from the beginning of the infection to the outbreak report is gradually increasing. Based on the analysis for ASF outbreaks, some policies and suggestions were put forward, such as improving the biosecurity level of the farms, as well as strengthening the supervision of breeding, transportation and slaughter.

Assessment of regional vulnerability to Africa swine fever in China during 2018/8-2019/7 based on data envelopment analysis method.

In this study, we introduce a vulnerability index to measure the regional ASF epidemic and present the ASF severity ratings of the 31 provinces of mainland China. The index is defined based on the data from the investigation, national statistical yearbook and reports. The data to be used include pig breeding, financial resources, human resources, epidemic information of ASF and price fluctuation from the 31 provinces. Then, we use the data envelopment analysis (DEA) method to define the vulnerability index, the relative severity value for each region, which quantitatively reflects the damage degree caused by the epidemic of ASF. The method allows us to provide a systematic classification for the regional vulnerability level of ASF in China. Using this index, we find that the vulnerability of the whole country is at a high level, and there is no regional aggregation phenomenon. The vulnerability level of the 31 provinces is quite different and the provinces with high vulnerability level are dispersive geographically. For the five major prevention and control zones for ASF in China, the northern region has the highest vulnerability level, while the eastern zoon level is the lowest.

Epidemiological Analysis of Coronavirus Disease 2019 (COVID-19) in 2 Cities in China Based on Public Data.

Based on the public data from the health departments of Tianjin and Shenzhen, we conducted a comparative analysis of the coronavirus disease 2019 (COVID-19) epidemic situation between these 2 cities. The aim of this study was to evaluate the role of public data in epidemic prevention and control of COVID-19, providing a scientific advice for the subsequent mitigation and containment of COVID-19 prevalence.

Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system.

The newly emerged severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coronavirus initiated a pneumonia outbreak (COVID-19) that rapidly spread worldwide and quickly became a public health emergency of international concern; However to date, except Remdesivir, there are no clinically approved specific or effective medicines to prevent or treat COVID-19. Therefore, the development of novel treatments against coronavirus infections caused by the current SARS-CoV-2 virus, as well as other highly pathogenic human coronaviruses, represents an urgent unmet need. Stimulator of interferon genes (STING) plays a central role in host defense mechanisms against microbial infections. STING activation leads to the induction of both type I interferon and autophagy responses, which elicit strong inhibitory effect against the infections caused by a broad range of microbial pathogens. However, whether STING activation can impact infections from SARS-CoV-2 or other coronaviruses remains largely unknown. In this study, we investigated the anti-coronavirus activity triggered by STING activation. We discovered that dimeric amidobenzimidazole (diABZI), a synthetic small molecule STING receptor agonist, showed potent anti-coronavirus activity against both the common cold human coronavirus 229E (HCoV-229E) and SARS-CoV-2 in cell culture systems. In addition, we demonstrated that the antiviral activity of diABZI was dependent on the interferon pathway in HCoV-229E infected normal human fibroblast lung cells (MRC-5) and reconstituted primary human airway air-liquid interface (ALI) cultures. Furthermore, low-dose of diABZI treatment at 0.1 µM effectively reduced the SARS-CoV-2 viral load at the epithelial apical surface and prevented epithelial damage in the reconstituted primary human bronchial airway epithelial ALI system. Our findings have thus revealed the therapeutic potential of STING agonists, such as diABZI, as treatments for SARS-CoV-2 and other human coronavirus infections.

Application of polyamide 6 microfiber non-woven fabrics in the large-scale production of all-solid-state lithium metal batteries.

All-solid-state electrolytes have received extensive attention due to their excellent safety and good electrochemical performance. However, due to the harsh conditions of the preparation process, the commercial production of all-solid-state electrolytes remains a challenge. The outbreak of the novel coronavirus pneumonia (COVID-19) has caused great inconvenience to people, while also allowing soft, lightweight and mass-producible non-woven fabrics in masks come into sight. Here, a polymer/polymer solid composite electrolyte is obtained by introducing the polyamide 6 (PA6) microfiber non-woven fabric into PEO polymer through the hot-pressing method. The addition of the PA6 non-woven fabric with lithium-philic properties can not only reduce the crystallinity of the polymer, but also provide more functional transmission sites and then promote the migration of lithium ions at the molecular level. Moreover, due to the sufficient mechanical strength and flexibility of the PA6 non-woven fabric, the composite electrolyte shows excellent inhibition ability of lithium dendrite growth and high electrochemical stability. The novel design concept of introducing low-cost and large-scale production of non-woven fabrics into all-solid-state composite electrolytes to develop high-performance lithium metal batteries is attractive, and can also be broadened to the combination of different types of polymers to meet the needs of various batteries.

Initial chest CT findings in COVID-19: correlation with clinical features.

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).