Cruise tourism in the context of COVID-19: Dilemmas and solutions.

COVID-19 cases on international cruise ships have attracted extensive attention from the international community as well as the world's tourism and shipping industry. This virus highlighted the plight that must be faced by cruise ships in complicated times and situations such as pandemics. The comparative method is adopted to analyze the management measures taken by the "Diamond Princess", "Costa Serena", "Westerdam" and "Grand Princess" cruises in response to the COVID-19 pandemic and then to summarize the common dilemmas faced by these cruise ships, including defects of their internal environment, unclear health-care obligations during an epidemic, weak collaboration between the parties involved and their limited performance, and widespread infodemic and unfavorable public opinion. Given these dilemmas, measures are suggested to deal with the "cruise dilemma", including establishing and defining isolation standards on boards, enhancing the capacity of international organizations, the international community's joint response to the pandemic, promoting cooperation between countries, building an effective mechanism for the broad participation of the whole society, and standardizing the release of information and reasonably guiding public social opinion.

Development and characterization of a new monoclonal antibody against SARS-CoV-2 NSP12 (RdRp).

SARS-CoV-2 NSP12, the viral RNA-dependent RNA polymerase (RdRp), is required for viral replication and is a therapeutic target to treat COVID-19. To facilitate research on SARS-CoV-2 NSP12 protein, we developed a rat monoclonal antibody (CM12.1) against the NSP12 N-terminus that can facilitate functional studies. Immunoblotting and immunofluorescence assay (IFA) confirmed the specific detection of NSP12 protein by this antibody for cells overexpressing the protein. Although NSP12 is generated from the ORF1ab polyprotein, IFA of human autopsy COVID-19 lung samples revealed NSP12 expression in only a small fraction of lung cells including goblet, club-like, vascular endothelial cells, and a range of immune cells, despite wide-spread tissue expression of spike protein antigen. Similar studies using in vitro infection also generated scant protein detection in cells with established virus replication. These results suggest that NSP12 may have diminished steady-state expression or extensive posttranslation modifications that limit antibody reactivity during SARS-CoV-2 replication.

Construction and characterization of two SARS-CoV-2 minigenome replicon systems.

The ongoing COVID-19 pandemic severely impacts global public health and economies. To facilitate research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virology and antiviral discovery, a noninfectious viral replicon system operating under biosafety level 2 containment is warranted. We report herein the construction and characterization of two SARS-CoV-2 minigenome replicon systems. First, we constructed the IVT-CoV2-Rep complementary DNA template to generate a replicon messenger RNA (mRNA) with nanoluciferase (NLuc) reporter via in vitro transcription (IVT). The replicon mRNA transfection assay demonstrated a rapid and transient replication of IVT-CoV2-Rep in a variety of cell lines, which could be completely abolished by known SARS-CoV-2 replication inhibitors. Our data also suggest that the transient phenotype of IVT-CoV2-Rep is not due to host innate antiviral responses. In addition, we have developed a DNA-launched replicon BAC-CoV2-Rep, which supports the in-cell transcription of a replicon mRNA as initial replication template. The BAC-CoV2-Rep transient transfection system exhibited a much stronger and longer replicon signal compared to the IVT-CoV2-Rep version. We also found that a portion of the NLuc reporter signal was derived from the spliced BAC-CoV2-Rep mRNA and was resistant to antiviral treatment, especially during the early phase after transfection. In summary, the established SARS-CoV-2 transient replicon systems are suitable for basic and antiviral research, and hold promise for stable replicon cell line development with further optimization.

SARS-CoV-2 pseudovirus infectivity and expression of viral entry-related factors ACE2, TMPRSS2, Kim-1, and NRP-1 in human cells from the respiratory, urinary, digestive, reproductive, and immune systems.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of syndromes involving multiple organ systems and is primarily mediated by viral spike (S) glycoprotein through the receptor-binding domain (RBD) and numerous cellular proteins including ACE2, transmembrane serine protease 2 (TMPRSS2), kidney injury molecule-1 (Kim-1), and neuropilin-1 (NRP-1). In this study, we examined the entry tropism of SARS-CoV-2 and SARS-CoV using S protein-based pseudoviruses to infect 22 cell lines and 3 types of primary cells isolated from respiratory, urinary, digestive, reproductive, and immune systems. At least one cell line or type of primary cell from each organ system was infected by both pseudoviruses. Infection by pseudoviruses is effectively blocked by S1, RBD, and ACE2 recombinant proteins, and more weakly by Kim-1 and NRP-1 recombinant proteins. Furthermore, cells with robust SARS-CoV-2 pseudovirus infection had strong expression of either ACE2 or Kim-1 and NRP-1 proteins. ACE2 glycosylation appeared to be critical for the infections of both viruses as there was a positive correlation between infectivity of either SARS-CoV-2 or SARS-CoV pseudovirus with the level of glycosylated ACE2 (gly-ACE2). These results reveal that SARS-CoV-2 cell entry could be mediated by either an ACE2-dependent or -independent mechanism, thus providing a likely molecular basis for its broad tropism for a wide variety of cell types.

Challenges and Approaches of the Global Governance of Public Health Under COVID-19.

Public health events, as the common concern faced by the international community, call for the joint response from all mankind. The outbreak of the COVID-19 has highlighted the problems confronting the global governance of international public health, such as limited functions of international organizations and difficulties in achieving objectives, poor collaboration between governance subjects and their limited performance, overlapping legal basis of governance and blurred core function, and lack of solutions to special problems. The corresponding approaches can be taken to improve the efficiency of the governance of global public health, including supporting the role of international organizations to achieve the objectives, enhancing coordination among international governance subjects to form synergy, promoting the compliance with IHR2005 to avoid conflict of law application and upholding the vision of a community with a shared future for mankind to jointly respond to the special problems.

Digital twins-based remote semi-physical commissioning of flow-type smart manufacturing systems.

The COVID-19 has become a global pandemic that dramatically impacted human lives and economic activities. Due to the high risk of getting affected in high-density population areas and the implementation of national emergency measures under the COVID-19 pandemic, both travel and transportation among cities become difficult for engineers and equipment. Consequently, the costly physical commissioning of a new manufacturing system is greatly hindered. As an emerging technology, digital twins can achieve semi-physical simulation to avoid the vast cost of physical commissioning of the manufacturing system. Therefore, this paper proposes a digital twins-based remote semi-physical commissioning (DT-RSPC) approach for open architecture flow-type smart manufacturing systems. A digital twin system is developed to enable the remote semi-physical commissioning. The proposed approach is validated through a case study of digital twins-based remote semi-physical commissioning of a smartphone assembly line. The results showed that combining the open architecture design paradigm with the proposed digital twins-based approach makes the commissioning of a new flow-type smart manufacturing system more sustainable.

COVID-19 With Preexisting Hypercoagulability Digestive Disease.

The outbreak of coronavirus disease of 2019 (COVID-19) has become a global public health and economic crisis. The advent of hypercoagulability and thrombotic complications can substantially influence the prognosis of COVID-19 patients. In this review, we elaborate on the clinical findings, potential underlying pathogenesis, and therapeutic strategy of hypercoagulability and thromboembolism in COVID-19, particularly focusing on the COVID-19 patients with preexisting digestive hypercoagulability disease.

Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development.

Clinical characteristics of coronavirus disease (COVID-19) patients with gastrointestinal symptoms: A report of 164 cases.

Objective: To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods: The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results: In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion: In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.

Clinical characteristics and risk factors for liver injury in COVID-19 patients in Wuhan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. We investigated the clinical characteristics and risk factors for liver injury in COVID-19 patients in Wuhan by retrospectively analyzing the epidemiological, clinical, and laboratory data for 218 COVID-19 patients and identifying the risk factors for liver injury by multivariate analysis. AIM: To investigate the clinical characteristics and risk factors for liver injury in COVID-19 patients in Wuhan. METHODS: The 218 patients included 94 males (43.1%), aged 22 to 94 (50.1 ± 18.4) years. Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were present in 42 (53.2%) and 36 (45.6%) cases, respectively, and 79 (36.2%) patients had abnormally elevated transaminase levels at admission. Patients with liver injury were older than those with normal liver function by a median of 12 years, with a significantly higher frequency of males (68.4% vs 28.8%, P < 0.001) and more coexisting illnesses (48.1% vs 27.3%, P = 0.002). Significantly more patients had fever and shortness of breath (87.3% vs 69.8% and 29.1% vs 14.4%, respectively) in the liver injury group. Only 12 (15.2%) patients had elevated total bilirubin. ALT and AST levels were mildly elevated [1-3 × upper limit of normal (ULN)] in 86.1% and 92.9% of cases, respectively. Only two (2.5%) patients had an ALT or AST level > 5 × ULN. Elevated γ-glutamyl transpeptidase was present in 45 (57.0%) patients, and 86.7% of these had a γ-glutamyl-transpeptidase level < 135 U/L (3 × ULN). Serum alkaline phosphatase levels were almost normal in all patients. Patients with severe liver injury had a significantly higher frequency of abnormal transaminases than non-severe patients, but only one case had very high levels of aminotransferases. RESULTS: Multivariate analysis revealed that male sex, high D-dimer level, and high neutrophil percentage were linked to a higher risk of liver injury. The early stage of COVID-19 may be associated with mildly elevated aminotransferase levels in patients in Wuhan. Male sex and high D-dimer level and neutrophil percentage may be important predictors of liver injury in patients with COVID-19. CONCLUSION: Male sex and high D-dimer level and neutrophil percentage may be important predictors of liver injury in patients with COVID-19.

A drug screening toolkit based on the -1 ribosomal frameshifting of SARS-CoV-2.

The -1 ribosomal frameshifting is vital for the translation of the open reading frame (ORF)1b in SARS-CoV-2. The products of ORF1b participate in viral replication. Therefore, changing the frameshift frequency reduces the survival of the virus. This study aimed to successfully develop a toolkit for screening antiviral drugs. Finally, the FDA-approved drug library was screened, revealing that ivacaftor and (-)-Huperzine A worked well in changing the -1 ribosomal frameshifting of SARS-CoV-2 in vitro.

COVID-19 and the Digestive System.

The outbreak of novel coronavirus pneumonia in 2019 (Coronavirus disease 2019 [COVID-19]) is now threatening global public health. Although COVID-19 is principally defined by its respiratory symptoms, it is now clear that the virus can also affect the digestive system. In this review, we elaborate on the close relationship between COVID-19 and the digestive system, focusing on both the clinical findings and potential underlying mechanisms of COVID-19 gastrointestinal pathogenesis.

An evaluation of mathematical models for the outbreak of COVID-19.

Mathematical modelling performs a vital part in estimating and controlling the recent outbreak of coronavirus disease 2019 (COVID-19). In this epidemic, most countries impose severe intervention measures to contain the spread of COVID-19. The policymakers are forced to make difficult decisions to leverage between health and economic development. How and when to make clinical and public health decisions in an epidemic situation is a challenging question. The most appropriate solution is based on scientific evidence, which is mainly dependent on data and models. So one of the most critical problems during this crisis is whether we can develop reliable epidemiological models to forecast the evolution of the virus and estimate the effectiveness of various intervention measures and their impacts on the economy. There are numerous types of mathematical model for epidemiological diseases. In this paper, we present some critical reviews on mathematical models for the outbreak of COVID-19. Some elementary models are presented as an initial formulation for an epidemic. We give some basic concepts, notations, and foundation for epidemiological modelling. More related works are also introduced and evaluated by considering epidemiological features such as disease tendency, latent effects, susceptibility, basic reproduction numbers, asymptomatic infections, herd immunity, and impact of the interventions.