Children with allergic asthma sensitized to house dust mites getting better health during COVID-19 pandemic (preprint)

Background: Since December 2019, 2019 novel corona virus (2019-nCov) disease (COVID-19) has extended to most parts of China with more than 80 thousand cases. From Feb 1 to Mar 31 of 2020, all children were asked to stay indoors in China. Then how it affected allergic asthma (AA) sensitized to house dust mites (HDM) in children was interestingly to clarify. Objective: To investigate the changes of clinical characteristics of children with AA sensitized to HDM during COVID-19 pandemic. Method: The data including asthma symptom scores(SS), visual analog scores (VAS), asthma quality of life questionnaire (AQLQ) and medicine scores (MS) as well as respiratory infections, cares, staying up late and diets, collected from children with AA sensitized to HDM from Feb 1 to Mar 31 of 2019 and 2020 retrospectively, were analyzed. Results: There were 85 children with AA sensitized to HDM included in this research. Compared with SS, VAS, AQLQ and MS of the patients from Feb 1 to Mar 31 of 2019, SS, VAS, AQLQ and MS of the patients improved significantly (p<0.05) during COVID-19 pandemic. No respiratory infections occurred among them and they got better cares, had better diets and stayed up late less during COVID-19 pandemic. Conclusion: During COVID-19 pandemic, children with AA sensitized to HDM got better health for staying indoors, which might be associated with no respiratory infections, better cares, better diets and less staying up late.

Discovery and evaluation of active compounds from Xuanfei Baidu Formula against COVID-19 via SARS-Cov-2 Mpro (preprint)

Background The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is still a widespread concern. As one of the effective traditional Chinese medicine (TCM) formula, Xuanfei Baidu formula (XFBD) shows significant efficacy for treatment of COVID-19 patients. However, its antiviral compounds and mechanism are still unclear. Purpose: In this study, we explored the bioactive compounds of XFBD and its antiviral mechanism by integrating computational analysis and experimental testing. Methods Aiming at the SARS-CoV-2 main protease (Mpro), as a key target in virus replication, the fluorescence resonance energy transfer (FRET) assay was built to screen out satisfactory natural inhibitors from XFBD. The surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) were undertaken to verify the binding affinity of Mpro-ligand. Omicron BA.1.1 and BA.2 variants were used to evaluate the antiviral activity of the focused compounds in non-cytotoxicity concentrations. For introducing the molecular mechanism, computational modeling and NMR spectra were employed to predict the binding mode and binding site of Mpro-ligand. Results From a library of 83 natural compounds, acteoside, licochalcone B, licochalcone D, linoleic acid, and physcion showed the satisfactory inhibition effect on Mpro with IC50 from 1.93 to 42.96 µM, which were further verified by SPR. Showing the excellent binding affinity, acteoside was witnessed to gain valuable insights into the thermodynamic signatures by ITC and presented antiviral activity on Omicron BA.1.1 and BA.2.3 variants in vitro. The results revealed that acteoside inhibited Mpro via forming the hydrogen bond between 7-H of acteoside and Mpro. Conclusion Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insight into the identifications of SARS-CoV-2 Mpro natural inhibitors.

Epidemiological characteristics and spatial-temporal clustering of COVID-19 in Hebei Province. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To analyze the epidemiological characteristics and spatial-temporal clustering of coronavirus disease 2019(COVID-19)in Hebei Province in order to provide scientific basis for the formulation of prevention and control measures.

Epidemiological characteristics and incubation period of coronavirus disease 2019 in Anhui Province. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To analyze the epidemiological characteristics and incubation of coronavirus disease 2019(COVID-19)from Jan. 22 to Mar. 8, 2020 in Anhui Province, in order to provide the basis for further understanding of the transmission pattern of COVID-19 and formulating regional control measures.

Estimated effects of economic policies for COVID-19 on the leisure and recreation industry under public health interventions. (Special Issue: COVID-19 and tourism.)

The appropriate policy responses for COVID-19 are being vigorously debated, especially regarding whether there is a trade-off between containing the spread of the virus and reducing the economic recession. The aim of the paper is to examine the effect of various economic policies on the leisure and recreation industry under public health interventions during the pandemic. The researchers collect data for 131 countries/regions from February to October 2020 and employ fixed-effects models to examine the impact of economic policies after controlling for public health interventions and country- and time-fixed effects. Results show that, with an impact lag, economic policies significantly promote current-date leisure and recreation activities under public health intervention;this effect peaks after around one month, and the two policies mutually reinforce each other in the medium term. The positive effect of economic policies ranges from 5 to 11%, depending on the magnitude of public health interventions. With regard to the different categories of measures, monetary policies have an immediate positive announcement effect while fiscal policies significantly promote leisure and recreation activities, though with a response lag. In addition, this study discusses the implications for the recovery of the leisure and recreation industry under pandemic crisis from a policy perspective.

Pandemic Arbitrage in Foreign Direct Investments: A Perspective on the Modes of Entry (preprint)

Foreign Direct Investments (FDI) are often considered long-term and less sensitive to global shocks as they involve large amounts of capital investment that are costly to reverse. This study examines whether a pandemic arbitrage through “distance” in COVID-19 infection rates impacts FDI. Using bilateral FDI inflows data from January 2019 to December 2020, we show that COVID-19 pandemic shock deterred global FDI mainly through the greenfield FDI mode of entry. Our results also show that strong social connections and loose COVID-19 policy stringency alleviates the pandemic’s effect on FDI, especially for M&As.

Risk-adapted treatment strategy for COVID-19 patients. (Coronavirus (COVID-19) collection.)

Background: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease (COVID-19). The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19.

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor (preprint)

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

Development of tree-like nanofibrous air filter with durable antibacterial property

High filtration performance and antibacterial property have been the main concerns of air filters. In this work, the silver nanoparticles (AgNPs) were produced by liquid phase reduction method and were added into polyvinylidene fluoride (PVDF) solutions at a ratio of 0.2%, 0.4%, 0.6%, 0.8%, and 1% for electrospinning. Nanofibers with the tree-like structure were fabricated by controlling the processing parameters. Therefore, a tree-like AgNPs/PVDF nanofiber membrane containing AgNPs was successfully developed. The AgNPs solutions were analyzed by UV-vis absorption spectrum to determine the size of AgNPs, and the nanofiber membranes were also evaluated in terms of morphology, structure, hydrophobic property, filtration performance, and antibacterial property. The results showed that the size of AgNPs was approximately 10 nm, the average diameters of branch-like fibers and stem-like fibers were about 30.8 nm and between 90 nm with 140 nm, respectively. The addition of AgNPs did not change the hydrophobic property of the PVDF nanofiber membrane;the filtration efficiency of AgNPs/PVDF nanofiber membrane was 99.95 ∼ 99.97% and the lowest pressure drop was 137.5 Pa;the bacterial reduction rates (BR) value against for S.aureus and E.coli were kept at a level of higher than 99.6% after exposure to sunlight for two weeks. Therefore, a kind of air filter with high filtration performance and durable antibacterial property was successfully developed by adding AgNPs and by creating tree-like structure fibers.

Dating the emergence of the first case of COVID-19 with flights: a retrospective modelling study (preprint)

Commercial flights contributed to the early-stage international transmission of SARS-CoV-2. Understanding the effect of international and inter-state flights on virus transmission is important to evaluate the initial response of the outbreak. This study investigated the likely date of the emergence of the first COVID-19 case. We constructed a geographical-structured epidemiology model, integrating 2541 province-level units, 250 country-level units, and 26,094,036 flight plans to evaluate the possible date of the emergence of the first case. Using the model, we estimated the number of cumulative deaths and the date of first death caused by COVID-19 in different countries. The pattern of the three parameters we evaluated suggests a high likelihood of the emergence of the first case of COVID-19 be around September 15 and September 22, 2019. 

SARS-Cov-2-, HIV-1-, Ebola-neutralizing and anti-PD1 clones are predisposed (preprint)

Antibody repertoire refers to the totality of the superbly diversified antibodies within an individual to cope with the vast array of possible pathogens. Despite this extreme diversity, antibodies of the same clonotype, namely public clones, have been discovered among individuals. Although some public clones could be explained by antibody convergence, public clones in naive repertoire or virus-neutralizing clones from not infected people were also discovered. All these findings indicated that public clones might not occur by random and they might exert essential functions. However, the frequencies and functions of public clones in a population have never been studied. Here, we integrated 2,449 Rep-seq datasets from 767 donors and discovered 5.07 million public clones - ~10% of the repertoire are public in population. We found 38 therapeutic clones out of 3,390 annotated public clones including anti-PD1 clones in healthy people. Moreover, we also revealed clones neutralizing SARS-CoV-2, Ebola, and HIV-1 viruses in healthy individuals. Our result demonstrated that these clones are predisposed in the human antibody repertoire and may exert critical functions during particular immunological stimuli and consequently benefit the donors. We also implemented RAPID - a Rep-seq Analysis Platform with Integrated Databases, which may serve as a useful tool for others in the field.

Screening and Analysis of COVID-19 cases in non-epidemic areas: A Retrospective Study (preprint)

Objective: To compare the epidemiological and clinical characteristics of confirmed and suspected corona virus disease 2019 (COVID-19) cases via the process of “triage-screening-isolation-transfer” in the hospitals of non-epidemic areas.Methods: The general data, epidemiological history, clinical symptoms, laboratory examination, and chest computed tomography (CT) imaging characteristics of 38 patients with suspected COVID-19, admitted between January 21 and March 5, 2020, were analyzed.Results: According to the results of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) ribonucleic acid (RNA) testing, the patients were divided into study group (RNA positive) and control group (RNA negative). Ultimately, 8 cases were RNA-positive and diagnosed as CDVID-19, and 30 cases were negative. Approximately half of the patients in the study group returned to Chongqing from Wuhan; this number was significantly larger than that of the control group (P<0.05). The number of subjects in close contact with the confirmed cases with SARS-CoV-2 RNA-positive and the incidence of aggregation was significantly larger in the study group than in the control group (both P<0.05). The clinical symptom of the study group was mainly low fever (with or without cough). The patients with decreased white blood cells (WBC) in the study group were significantly more than those in the control group (P<0.05). Both group had reduced lymphocytes (Lym) but the number of patients with increased C-reactive protein (CRP) in the study group was significantly more than that in the control group (P<0.05). There were different degrees of chest CT abnormalities in both study and control group (P > 0.05). Conclusion: The epidemiological investigations in screening for infectious diseases is crucial. The risk of infection was high from the primary epidemic area and/or in close contact with the confirmed case. The most common form of clustering occurrence was family aggregation. CDVID-19 was mainly characterized by fever and respiratory symptoms, although asymptomatic infection may also occur. Decreased WBC, decreased Lym, and increased CRP are common characteristics but can also be combined with other respiratory tract virus infections. COVID 19 screening by chest CT alone had certain limitations in non- epidemic areas.

Development and Multicenter Performance Evaluation of The First Fully Automated SARS-CoV-2 IgM and IgG Immunoassays (preprint)

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid tests. However, there are many limitations of nucleic acid tests, including low throughput and high rates of false negatives. More sensitive and accurate tests to effectively identify infected patients are needed. METHODS: This study has developed fully automated chemiluminescent immunoassays (CLIA) to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients with diseases other than COVID-19, and 586 donors of a normal population. Clinical sensitivity was assessed on 503 confirmed cases of SARS-CoV-2 by RT-PCR and 52 suspected cases. RESULTS: The assays demonstrated satisfied assay precision with coefficient of variation (CV) of less than 4.45%. Inactivation of specimen does not affect assay measurement. SARS-CoV-2 IgM shows clinical specificity of 97.33% and 99.49% for hospitalized patients and normal population respectively. SARS-CoV-2 IgG shows clinical specificity of 97.43% and 99.15% for the hospitalized patients and the normal population respectively. SARS-CoV-2 IgM and IgG show clinical sensitivity of 85.88% and 96.62% respectively for confirmed SARS-Cov-2 infection with RT-PCR, of 73.08% and 86.54% respectively for suspected cases. CONCLUSIONS: we have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.

Structural basis for the inhibition of COVID-19 virus main protease by carmofur, an antineoplastic drug (preprint)

The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 M) and it is a promising lead compound to develop new antiviral treatment for COVID-19.

Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target (preprint)

A novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-[A]. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified {beta}-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp. One Sentence SummaryStructure of 2019-nCov RNA polymerase.

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin (preprint)

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.