SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium.

OBJECTIVE: In this study, we focused on the interaction between SARS-CoV-2 and host Type I Interferon (IFN) response, so as to identify whether IFN effects could be influenced by the products of SARS-CoV-2. METHODS: All the structural and non-structural proteins of SARS-CoV-2 were transfected and overexpressed in the bronchial epithelial cell line BEAS-2B respectively, and typical antiviral IFN-stimulated gene (ISG) ISG15 expression was detected by qRT-PCR. RNA-seq based transcriptome analysis was performed between control and Spike (S) protein-overexpressed BEAS-2B cells. The expression of ACE2 and IFN effector JAK-STAT signaling activation were detected in control and S protein-overexpressed BEAS-2B cells by qRT-PCR or/and Western blot respectively. The interaction between S protein with STAT1 and STAT2, and the association between JAK1 with downstream STAT1 and STAT2 were measured in BEAS-2B cells by co-immunoprecipitation (co-IP). RESULTS: S protein could activate IFN effects and downstream ISGs expression. By transcriptome analysis, overexpression of S protein induced a set of genes expression, including series of ISGs and the SARS-CoV-2 receptor ACE2. Mechanistically, S protein enhanced the association between the upstream JAK1 and downstream STAT1 and STAT2, so as to promote STAT1 and STAT2 phosphorylation and ACE2 expression. CONCLUSION: SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.

SWOT Analysis and Preliminary Study on Prevention and Control Management of Temporary Integrated Isolation Ward During COVID-19 Outbreak.

Background: The world faced crises of prevention and control and shortage of medical resources during the COVID-19 (Corona Virus Disease 2019) outbreak. The establishment of temporary integrated isolation wards in hospitals, which is universal and representative in China, is one of the most-effective strategies in solving these problems according to China's experiences. Aim: To conduct a preliminary study on the establishment of a temporary integrated isolation ward during the outbreak of COVID-19 and to evaluate related impact. Methods: SWOT analysis was used to analyze the advantages, disadvantages, opportunities, and risks in the establishment of the temporary integrated isolation ward, and corresponding corrective measures were made according to the analysis results. Findings: The ward has formulated more than 10 related work procedures and prevention and control measures. A total of 93 patients with 18 critically ill patients were admitted for treatment and isolation. They were all evaluated based on established procedures and protocols. Twenty-four supplementary nucleic acid tests were ordered and conducted. One new patient with COVID-19 was confirmed and was successfully transferred to the designated COVID-19 infectious control hospital. There were no missed diagnosis or misdiagnosis, no cross-infection of patients, no cluster outbreak, and no infection of medical workers during the entire process. Conclusion: SWOT analysis is helpful in guiding the establishment of a temporary integrated isolation ward and the formulation of prevention and control measures in Hebei General Hospital during the COVID-19 outbreak. It provides the guidance and reference of significance for the establishment of similar types of wards in the future.

COVID-19-Associated Acute Brain Dysfunction Related to Sepsis.

In global term, as of November 30, 2020, over 30 million people has been infected by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10,000,000 of them died of acute organ failure. Our reviews have shown that coronavirus disease 2019 (COVID-19) patients with pneumonia and acute respiratory distress syndrome (ARDS) have life-threatening acute brain dysfunction (ABD), ranging from altered mental status/delirium to stupor/coma. Altered mental status/delirium was the most common manifestation of ABD caused by severe COVID-19. The prevalence of altered mental status and/or delirium was up to 66-79.5%, and prevalence of coma was 10%. The most common clinical type of COVID-19-associated ABD was COVID-19-associated acute stroke including ischemic and hemorrhagic stroke (n > 350 cases), followed by COVID-19-associated encephalopathy (n > 200 cases), and COVID-19-associated central nervous system (CNS) infection (n > 70 cases). According to the Sepsis-3 criteria, we confess that severe COVID-19-associated ABD with ARDS and altered mental status is related to sepsis. Moreover, we also review the diagnosis and treatment of COVID-19-associated ABD with sepsis. In view of the fact that COVID-19 is at the peak of epidemic worldwide, we hope that this review will provide evidence of COVID-19 sepsis threating to the brain dysunction. Thus, recognizing the COVID-19-associated ABD related to sepsis is very important for early empirical combination therapy to survive severe COVID-19.

Gastrointestinal involvement of COVID-19 and potential faecal transmission of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found initially in Wuhan, China in early December 2019. The pandemic has spread to 216 countries and regions, infecting more than 23310 000 people and causing over 800 000 deaths globally by Aug. 24, 2020, according to World Health Organization (https://www.who.int/emergencies/diseases/ novel-coronavirus-2019). Fever, cough, and dyspnea are the three common symptoms of the condition, whereas the conventional transmission route for SARS-CoV-2 is through droplets entering the respiratory tract. To date, infection control measures for COVID-19 have been focusing on the involvement of the respiratory system. However, ignoring potential faecal transmission and the gastrointestinal involvement of SARS-CoV-2 may result in mistakes in attempts to control the pandemic.