Highlights d Human ACE2 knockin mice were generated by using CRISPR/Cas9 technology d SARS-CoV-2 leads to robust replication in lung, trachea, and brain d SARS-CoV-2 causes interstitial pneumonia and elevated cytokine in aged hACE2 mice d High dose of SARS-CoV-2 can establish infection via intragastric route in hACE2 mice

Phone No: +86 18071093208 Word count of abstract: 215 Word count of text: 2483 Highlights  The immune status is significantly different between severe and non-severe COVID-19  The decrease of T lymphocyte correlated with the course of patients with COVID-19  The level of T lymphocyte is an indicator for severity and prognosis of COVID-19Abstract: Objectives: To explore the clinical course and its dynamic features of immune status in COVID-19 patients and find predictors correlated with severity and prognosis of COVID-19. Methods: The electronic medical records of 204 patients with COVID-19 pneumonia confirmed by nucleic acid testing were retrospectively collected and analyzed. Results: All Patients were divided into severe (69) and non-severe group (135). Lymphocyte subsets count, including CD3+ T cell, CD4+ T cell, CD8+ T cell, B cell (CD19+) and NK J o u r n a l P r e -p r o o f cell (CD16+56+), were significantly lower in severe group (P＜0.001). The dynamic levels of T lymphocytes in severe group were significantly lower from disease onset, but in the improved subgroup the value of T lymphocyte began to increase after about 15-day treatment and finally returned to the normal level. The cut-off value of the counts of CD3+ (576), CD4+ (391) and CD8+ (214) T cell were calculated and indicated significantly high sensitivity and specificity for severity of COVID-19. Conclusion: Our results shown that the decrease of CD3+, CD4+ and CD8+ T lymphocyte correlated with the course of patients with COVID-19 pneumonia, especially in severe cases. The level of T lymphocyte could be used as an indicator for prediction of severity and prognosis of patients with COVID-19 pneumonia. The application of glucocorticoid should be cautious in severe cases. IgE, IU/mL <100 23.5 (17.3-80.8) 21.9 (17.3-84.3) 30.85 (17.3-68.9) 0.707J o u r n a l P r e -p r o o f

Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods: Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results: 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80 ±10.82 days, and was significantly longer in progression patients (28.60 ±7.55 day). Conclusion: CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as "covert transmitter", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Doping effect of diamond nanoparticles on the superconducting properties of MgB 2 bulk material has been studied. It is found that the superconducting transition temperature T c of MgB 2 is suppressed by the diamond-doping, however, the irreversibility field H irr and the critical current density J c are systematically enhanced. Microstructural analysis shows that the diamond-doped MgB 2 superconductor consists of tightly-packed MgB 2 nano-grains (~50-100 nm) with highly-dispersed and uniformly-distributed diamond nanoparticles (~10-20 nm) inside the grains. High density of dislocations and diamond nanoparticles may take the responsibility for the enhanced flux pinning in the diamond-doped MgB 2 . *Corresponding author: email: c.cheng@unsw.edu.au 2 I IntroductionSince the discovery of superconductivity at 39 K in MgB 2 [1], significant progress has been made in improving the performance of MgB 2 materials [2][3][4][5][6][7]. MgB 2 offers the possibility of wide engineering applications in the temperature range 20-30 K, where conventional superconductors, such as Nb 3 Sn and Nb-Ti alloy, cannot play any roles due to their low T c .However, the realization of large-scale applications for MgB 2 -based superconductivity technology essentially relies on the improvement of the pinning behaviour of MgB 2 in high fields. As it has poor grain connection and a lack of pinning centres, MgB 2 often exhibits a rapid decrease in critical current density, J c , in high magnetic fields. Fortunately, through the formation of nanoparticle structures in bulk MgB 2 [3][4][5] and thin films [7], the problem of the poor grain connection can be solved, and the flux pinning force can also be significantly enhanced due to an increase of pinning centres served by grain boundaries. In order to improve further the performance of MgB 2 , it is necessary to introduce more pinning centres, especially those consisting of nano-sized second-phase inclusions which often provide strong pinning forces.Nano-diamond, prepared by the detonation technique, has been widely used as an additive to improve the performance of various materials [8]. However, nano-diamond-doping effect on the superconducting properties MgB 2 has never been reported although carbon with other forms has been used as dopants in MgB 2 [9][10][11]. The high dispersibility of the nanodiamond powder makes it possible to form a high density of nano-inclusions in MgB 2 matrix.In this article, we have investigated the doping effect of nano-diamond on the superconducting properties of MgB 2 . Our results show that the nano-diamond-doped MgB 2 consists of tightly-packed MgB 2 nano-grains (~50-100 nm) with diamond nanoparticles (~10-20 nm) wrapped within the grains. This unique microstructure provides the samples with a good grain connection for the MgB 2 phase and a high density of flux-pinning centres served 3 by the diamond nanoparticles. Compared to the MgB 2 bulk materials doped with other nanoparticles [3][4][5][6][7], the irreversibility line has been significantly improved and ...