Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak

Introduction The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak.

Introduction: The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods: Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results: We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion: Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

RBM24 inhibits the translation of SARS-CoV-2 polyproteins by targeting the 5'-untranslated region.

SARS-CoV-2 is a betacoronavirus with single-stranded positive-sense RNA, which is a serious global threat to human health. Understanding the molecular mechanism of viral replication is crucial for the development of antiviral drugs. The synthesis of viral polyproteins is a crucial step in viral progression. The synthesis of viral polyproteins in coronaviruses is regulated by the 5'-untranslated region (UTR); however, the detailed regulatory mechanism needs further investigation. The present study demonstrated that the RNA binding protein, RBM24, interacts with the RNA genome of SARS-CoV-2 via its RNA recognition submotifs (RNPs). The findings revealed that RBM24 recognizes and binds to the GUGUG element at stem-loop 4 (SL4) in the 5'-UTR of SARS-CoV-2. The interaction between RBM24 and 5'-UTR prevents 80S ribosome assembly, which in turn inhibits polyproteins translation and the replication of SARS-CoV-2. Notably, other RNA viruses, including SARS-CoV, MERS-CoV, Ebolavirus, rhinovirus, West Nile virus, Zika virus, Japanese encephalitis virus, yellow fever virus, hepatitis C virus, and human immunodeficiency virus-1 also contain one or several G(U/C/A)GUG sequences in the 5'-UTR, which is also targeted by RBM24. In conclusion, the present study demonstrated that RBM24 functions by interacting with the 5'-UTR of SARS-CoV-2 RNA, and elucidated that RBM24 could be a host restriction factor for SARS-CoV-2 and other RNA viruses.

A Predictive Decision Analytics Approach for Primary Care Operations Management: A Case Study of Double-Booking Strategy Design and Evaluation

Primary care plays a vital role for individuals and families in accessing care, keeping well, and improving quality of life. However, the complexities and uncertainties in the primary care delivery system (e.g., patient no-shows/walk-ins, staffing shortage, COVID-19 pandemic) have brought significant challenges in its operations management, which can potentially lead to poor patient outcomes and negative primary care operations (e.g., loss of productivity, inefficiency). This paper presents a decision analytics approach developed based on predictive analytics and hybrid simulation to better facilitate management of the underlying complexities and uncertainties in primary care operations. A case study was conducted in a local family medicine clinic to demonstrate the use of this approach for patient no-show management. In this case study, a patient no-show prediction model was used in conjunction with an integrated agent-based and discrete-event simulation model to design and evaluate double-booking strategies. Using the predicted patient no-show information, a prediction-based double-booking strategy was created and compared against two other strategies, namely random and designated time. Scenario-based experiments were then conducted to examine the impacts of different double-booking strategies on clinic's operational outcomes, focusing on the trade-offs between the clinic productivity (measured by daily patient throughput) and efficiency (measured by visit cycle and patient wait time for doctor). The results showed that the best productivity-efficiency balance was derived under the prediction-based double-booking strategy. The proposed hybrid decision analytics approach has the potential to better support decision-making in primary care operations management and improve the system's performance. Further, it can be generalized in the context of various healthcare settings for broader applications.

AbAgIntPre: A deep learning method for predicting antibody-antigen interactions based on sequence information.

Introduction: Antibody-mediated immunity is an essential part of the immune system in vertebrates. The ability to specifically bind to antigens allows antibodies to be widely used in the therapy of cancers and other critical diseases. A key step in antibody therapeutics is the experimental identification of antibody-antigen interactions, which is generally time-consuming, costly, and laborious. Although some computational methods have been proposed to screen potential antibodies, the dependence on 3D structures still limits the application of these methods. Methods: Here, we developed a deep learning-assisted prediction method (i.e., AbAgIntPre) for fast identification of antibody-antigen interactions that only relies on amino acid sequences. A Siamese-like convolutional neural network architecture was established with the amino acid composition encoding scheme for both antigens and antibodies. Results and Discussion: The generic model of AbAgIntPre achieved satisfactory performance with the Area Under Curve (AUC) of 0.82 on a high-quality generic independent test dataset. Besides, this approach also showed competitive performance on the more specific SARS-CoV dataset. We expect that AbAgIntPre can serve as an important complement to traditional experimental methods for antibody screening and effectively reduce the workload of antibody design. The web server of AbAgIntPre is freely available at http://www.zzdlab.com/AbAgIntPre.

SARS-CoV-2 infection activates CREB/CBP in cellular cyclic AMP-dependent pathways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global coronavirus disease 2019 (COVID-19) pandemic that has affected the lives of billions of individuals. However, the host-virus interactions still need further investigation to reveal the underling mechanism of SARS-CoV-2 pathogenesis. Here, transcriptomics analysis of SARS-CoV-2 infection highlighted possible correlation between host-associated signaling pathway and virus. In detail, cAMP-protein kinase (PKA) pathway has an essential role in SARS-CoV-2 infection, followed by the interaction between cyclic AMP response element binding protein (CREB) and CREB-binding protein (CBP) could be induced and leading to the enhancement of CREB/CBP transcriptional activity. The replication of Delta and Omicron BA.5 were inhibited by about 49.4% and 44.7% after knockdown of CREB and CBP with small interfering RNAs, respectively. Furthermore, a small organic molecule naphthol AS-E (nAS-E), which targets on the interaction between CREB and CBP, potently inhibited SARS-CoV-2 wild-type (WT) infection with comparable the half-maximal effective concentration (EC50 ) 1.04 µM to Remdesivir 0.57 µM. Compared with WT virus, EC50 in Calu-3 cells against Delta, Omicron BA.2, and Omicron BA.5 were, on average, 1.5-fold, 1.1-fold, and 1.5-fold higher, respectively, nAS-E had a satisfied antiviral effect against Omicron variants. Taken together, our study demonstrated the importance of CREB/CBP induced by cAMP-PKA pathway during SARS-CoV-2 infection, and further provided a novel CREB/CBP interaction therapeutic drug targets for COVID-19.

Landscape of Peripheral Blood Mononuclear Cells and Soluble Factors in Severe COVID-19 Patients With Pulmonary Fibrosis Development.

Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.

Comparison of viral propagation and drug response among SARS-CoV-2 VOCs using replicons capable of recapitulating virion assembly and release.

Several variants of concern (VOCs) have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first isolated in January 2020. Due to mutations in the spike (S) protein, these VOCs have evolved to enhance viral infectivity and immune evasion. However, whether mutations of the other viral proteins lead to altered viral propagation and drug resistance remains obscure. The replicon is a noninfectious viral surrogate capable of recapitulating certain steps of the viral life cycle. Although several SARS-CoV-2 replicons have been developed, none of them were derived from emerging VOCs and could only recapitulate viral genome replication and subgenomic RNA (sgRNA) transcription. In this study, SARS-CoV-2 replicons derived from the WIV04 strain and two VOCs (the Beta and Delta variants) were prepared by removing the S gene from their genomes, while other structural genes remained untouched. These replicons not only recapitulate viral genome replication and sgRNA transcription but also support the assembly and release of viral-like particles, as manifested by electron microscopic assays. Thus, the S-deletion replicon could recapitulate virtually all the post-entry steps of the viral life cycle and provides a versatile tool for measuring viral intracellular propagation and screening novel antiviral drugs, including inhibitors of virion assembly and release. Through the quantification of replicon RNA released into the supernatant, we demonstrate that viral intracellular propagation and drug response to remdesivir have not yet substantially changed during the evolution of SARS-CoV-2 from the WIV04 strain to the Beta and Delta VOCs.

Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.

An Optimization Framework to Study the Balance Between Expected Fatalities Due to COVID-19 and the Reopening of U.S. Communities

During the COVID-19 pandemic, communities faced two conflicting objectives: 1) minimizing infections among vulnerable populations with higher risk for severe illness and 2) enabling reopening to revive American livelihoods. The U.S. pandemic strategy myopically considered one objective at a time, with lockdowns that addressed the former, but was detrimental to the latter, and phased reopening that pursued the latter, but lost control over the former. How could we prioritize interventions to simultaneously minimize cases of severe illness and fatalities while reopening? A team of researchers anchored by the Center on Stochastic Modeling, Optimization, & Statistics (COSMOS), The University of Texas at Arlington, has formulated a computationally efficient optimization framework, referred to as COSMOS COVID-19 Linear Programming (CC19LP), to study the delicate balance between the expected fatality rate due to cases of severe illness and the level of normalcy in the community. The key to the CC19LP framework is a focus on “key contacts” that separate individuals at higher risk from the rest of the population. CC19LP minimizes expected fatalities by optimizing the use of available interventions, namely, COVID-19 testing, personal protective equipment (PPE), COVID-19 vaccines, and social precautions, such as distancing, handwashing, and face coverings. A C3.ai award-winning online CC19LP tool is accessible from the COSMOS COVID-19 project site (https://cosmos.uta.edu/projects/covid-19/) and has been tested for all 3142 U.S. county areas. Results are demonstrated for several metropolitan counties with a deeper investigation for Miami-Dade County in Florida. Note to Practitioners—In this article, a computationally fast optimization framework is presented to study the delicate balance between reopening U.S. communities and controlling severe cases of COVID-19 that lead to hospitalizations and fatalities. This framework can provide guidance to decision-makers on optimal intervention strategies for protecting high-risk individuals while reopening communities. This optimization framework demonstrates a practical approach to conduct decision-making in an uncertain environment and can be useful for the prioritization of resources and interventions in the case of future epidemics or pandemics. Resources on understanding and implementing the framework are publicly available, including an award-winning online optimization tool that automatically accesses county-level data from Census, Centers for Disease Control and Prevention (CDC), and Johns Hopkins COVID-19 repositories. [ FROM AUTHOR] Copyright of IEEE Transactions on Automation Science & Engineering is the property of IEEE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication.

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.

Functional connectivity of amygdala subregions predicts vulnerability to depression following the COVID-19 pandemic.

BACKGROUND: The amygdala is vital in processing psychological stress and predicting vulnerability or resilience to stress-related disorders. This study aimed to build the link between functional magnetic resonance imaging data obtained before the stress event and the subsequent stress-related depressive symptoms. METHODS: Neuroimaging data obtained before the coronavirus disease 2019 pandemic from 39 patients with major depressive disorder (MDD) and 61 health controls (HCs) were used in this study. The participants were divided retrospectively into four groups in accordance with the severity of depressive symptoms during the pandemic: remitted patients, non-remitted patients, depressed HCs (HCd) and non-depressed HCs (HCnd). Seed-based resting-state functional connectivity (rsFC) analyses of the amygdala and its subregions, including the centromedial (CM), the basolateral and the superficial (SF), were performed. RESULTS: Vulnerability to depression was suggested by decreased rsFC between the left CM amygdala and the bilateral lingual gyrus in the HCd group compared with the HCnd group, and decreased rsFC of the left CM or right SF amygdala with the precuneus and the postcentral gyrus in the HCd group compared with patients with MDD. No evidence supported the rsFC of the amygdala or its subregions as a biomarker for the resilience of patients with MDD to stress under antidepressant treatment. LIMITATIONS: Smaller sample size and no longitudinal neuroimaging data. CONCLUSIONS: Our findings suggested that the rsFC of amygdala subregions may represent a neurobiological marker of vulnerability to depression following stress.

Advancements in detection of SARS-CoV-2 infection for confronting COVID-19 pandemics.

As one of the major approaches in combating the COVID-19 pandemics, the availability of specific and reliable assays for the SARS-CoV-2 viral genome and its proteins is essential to identify the infection in suspected populations, make diagnoses in symptomatic or asymptomatic individuals, and determine clearance of the virus after the infection. For these purposes, use of the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for detection of the viral nucleic acid remains the most valuable in terms of its specificity, fast turn-around, high-throughput capacity, and reliability. It is critical to update the sequences of primers and probes to ensure the detection of newly emerged variants. Various assays for increased levels of IgG or IgM antibodies are available for detecting ongoing or past infection, vaccination responses, and persistence and for identifying high titers of neutralizing antibodies in recovered individuals. Viral genome sequencing is increasingly used for tracing infectious sources, monitoring mutations, and subtype classification and is less valuable in diagnosis because of its capacity and high cost. Nanopore target sequencing with portable options is available for a quick process for sequencing data. Emerging CRISPR-Cas-based assays, such as SHERLOCK and AIOD-CRISPR, for viral genome detection may offer options for prompt and point-of-care detection. Moreover, aptamer-based probes may be multifaceted for developing portable and high-throughput assays with fluorescent or chemiluminescent probes for viral proteins. In conclusion, assays are available for viral genome and protein detection, and the selection of specific assays depends on the purposes of prevention, diagnosis and pandemic control, or monitoring of vaccination efficacy.

The impact of COVID-19 on body-dissatisfied female university students.

OBJECTIVE: This study investigated the impact of COVID-19 on young women's disordered eating and their responses to online interventions to reduce disordered eating. METHOD: University students at risk of developing an eating disorder (N = 100) were randomly assigned to either receiving an online intervention to reduce disordered eating or not. Forty-one participants entered the study from September 2019 to March 2020 (pre-COVID) and 59 after physical distancing was introduced due to COVID pandemic (during COVID). Online assessments were conducted at baseline and 1-week follow up. RESULTS: There was a significant increase in weight concerns, disordered eating, and negative affect among participants entering the trial during COVID compared to pre-COVID. The increases in the first two variables remained when adjusting for baseline negative affect. No significant interactions between time, condition and COVID status were observed. DISCUSSION: Young women experienced increased levels of disordered eating after the onset of COVID. While no interactions with COVID were detected, changes to within-group effect sizes for disordered eating more than doubled for both online interventions and assessment from pre-COVID to during COVID, suggesting any attention to issues related to disordered eating in the context of reduced social contact may be beneficial.

Targeting mesenchymal stem cell therapy for severe pneumonia patients.

Pneumonia is the inflammation of the lungs and it is the world's leading cause of death for children under 5 years of age. The latest coronavirus disease 2019 (COVID-19) virus is a prominent culprit to severe pneumonia. With the pandemic running rampant for the past year, more than 1590000 deaths has occurred worldwide up to December 2020 and are substantially attributable to severe pneumonia and induced cytokine storm. Effective therapeutic approaches in addition to the vaccines and drugs under development are hence greatly sought after. Therapies harnessing stem cells and their derivatives have been established by basic research for their versatile capacity to specifically inhibit inflammation due to pneumonia and prevent alveolar/pulmonary fibrosis while enhancing antibacterial/antiviral immunity, thus significantly alleviating the severe clinical conditions of pneumonia. In recent clinical trials, mesenchymal stem cells have shown effectiveness in reducing COVID-19-associated pneumonia morbidity and mortality; positioning these cells as worthy candidates for combating one of the greatest challenges of our time and shedding light on their prospects as a next-generation therapy to counter future challenges.

COVID-19 and Perioperative Management Strategies for Gastrointestinal Surgery: An Experience From Jiaxing, China.

BACKGROUND: The coronavirus disease (COVID-19) was leading to a worldwide pandemic, which affected surgical operation. This study assessed the efficacy of perioperative management of patients scheduled for gastrointestinal surgery during COVID-19 pandemic of 2020. METHODS: We retrospectively analyzed 188 patients who underwent gastrointestinal surgery during the COVID-19 outbreak in Jiaxing, China. Perioperative data were collected, including data on pre-, intra-, and postoperative management strategies. The same data over the same period in 2019 were also collected for comparison. RESULTS: A total of 117, 63, and 8 patients underwent emergency, semi-elective, and elective surgeries, respectively. The locals: nonlocals ratio was significantly higher during this investigation period in 2020 than during the same period in 2019 (P < .05). After screening, 12 patients were identified as unqualified. The number of gastrointestinal surgeries was reduced in 2020. There were no differences in the ratio of emergency surgery or semi-elective surgery between in 2020 and in 2019. The elective surgery ratio between January 27 and February 28 was found to be lower in 2020 than in 2019 (P < .05). The disease spectra of emergency surgery and semi-elective surgery were similar. A total of 31 elective surgeries were postponed. There were five cases of short-term complications for emergency surgeries and two cases of short-term complications for semi-elective surgeries. No long-term complications or COVID-19 infection occurred in any of the cases, and no medical staff member was infected. CONCLUSION: Perioperative management strategies minimize the risk of nosocomial infection and reduce the influence of epidemics on gastrointestinal surgery.

The spatial transmission of SARS-CoV-2 in China under the prevention and control measures at the early outbreak.

BACKGROUND: Since severe acute respiratory syndrome coronavirus, 2 (SARS-CoV-2) was firstly reported in Wuhan City, China in December 2019, Novel Coronavirus Disease 2019 (COVID-19) that is caused by SARS-CoV-2 is predominantly spread from person-to-person on worldwide scales. Now, COVID-19 is a non-traditional and major public health issue the world is facing, and the outbreak is a global pandemic. The strict prevention and control measures have mitigated the spread of SARS-CoV-2 and shown positive changes with important progress in China. But prevention and control tasks remain arduous for the world. The objective of this study is to discuss the difference of spatial transmission characteristics of COVID-19 in China at the early outbreak stage with resolute efforts. Simultaneously, the COVID-19 trend of China at the early time was described from the statistical perspective using a mathematical model to evaluate the effectiveness of the prevention and control measures. METHODS: In this study, the accumulated number of confirmed cases publicly reported by the National Health Committee of the People's Republic of China (CNHC) from January 20 to February 11, 2020, were grouped into three partly overlapping regions: Chinese mainland including Hubei province, Hubei province alone, and the other 30 provincial-level regions on Chinese mainland excluding Hubei province, respectively. A generalized-growth model (GGM) was used to estimate the basic reproduction number to evaluate the transmissibility in different spatial locations. The prevention and control of COVID-19 in the early stage were analyzed based on the number of new cases of confirmed infections daily reported. RESULTS: Results indicated that the accumulated number of confirmed cases reported from January 20 to February 11, 2020, is well described by the GGM model with a larger correlation coefficient than 0.99. When the accumulated number of confirmed cases is well fitted by an exponential function, the basic reproduction number of COVID-19 of the 31 provincial-level regions on the Chinese mainland, Hubei province, and the other 30 provincial-level regions on the Chinese mainland excluding Hubei province, is 2.68, 6.46 and 2.18, respectively. The consecutive decline of the new confirmed cases indicated that the prevention and control measures taken by the Chinese government have contained the spread of SARS-CoV-2 in a short period. CONCLUSIONS: The estimated basic reproduction number thorough GGM model can reflect the spatial difference of SARS-CoV-2 transmission in China at the early stage. The strict prevention and control measures of SARS-CoV-2 taken at the early outbreak can effectively reduce the new confirmed cases outside Hubei and have mitigated the spread and yielded positive results since February 2, 2020. The research results indicated that the outbreak of COVID-19 in China was sustaining localized at the early outbreak stage and has been gradually curbed by China's resolute efforts.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.