Based on the Theory of Mastery Learning and Reinforcement theory: The relationship between online student engagement and skills test scores in Clinical Skills Course (preprint)

Background:  The sudden outbreak of the COVID-19 pandemic in 2019 has affected our lives in different ways. The teaching method of colleges and universities has changed from traditional face-to-face learning to online learning. Clinical skills teaching is one of the core contents of clinical medical teaching. The key to ensure that students have a good grasp of learning is to ensure that they have enough time to learn effectively.Based on the mastery learning theory and reinforcement theory, the mixed online and offline teaching mode is carried out, which not only has the flexibility and convenience of online teaching, but also provides students with better offline teacher-student interaction and practical operation practice,which is more suitable for practical courses such as clinical skills courses.Studies have shown that student engagement in face-to-face learning is directly related to academic record. Little research has been done on the relationship between online student engagement and academic performance. Objective: Based on mastery learning theory and reinforcement theory in the teaching of clinical skills courses, and to explore the impact of online student engagement on academic performance and its magnitude in Clinical Skills Course by constructing a structural equation model. Methods:  259 fourth-year clinical medicine students volunteered for the study. They watched the video of skill operation on the online learning platform and took the chapter test before the class.Then they entered the face-to-face class with teacher demonstration and guidance to practice the operation.Finally, we arrange an online comprehensive theory test and an offline skill operation test.Throughout the course, they can discuss the course content interactivelyon the online platform.Record their video viewing duration, times of chapter learning, times of discussions, chapter test scores, comprehensive test scores and offline skill test scores.Amos was used to construct structural equation model to analyze the data. Results:  The results showed that the model fits well(`c/df=1.565,GFI=0.984,AGFI=0.958,CFI=0.952,RMSEA=0.047);In Clinical Skills Course, applied learning behaviors (such as times of discussions, chapter test scores, comprehensive test scores) had a direct impact on clinical skills test scores, and the standardized path coefficient was 0.3 (p<0.05). Observational learning behaviors (such as video viewing duration and times of chapter learning) can directly affect applied learning behaviors, with a standardized path coefficient of 0.63 (p<0.05), and then indirectly affect clinical skills test scores through applied learning behaviors. Conclusion:  Based on mastery learning theory and reinforcement theory in the online and offline blended clinical skills course teaching,enhancing observational learning behavior can improve the scores of applied learning behavior, and thus improve the scores of clinical skills examination.

Dynamic changes in the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its association with disease severity (preprint)

Background The antibiotic resistome is the collection of all the antibiotic resistance genes (ARGs) present in an individual. Whether an individual’s susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is influenced by their respiratory tract antibiotic resistome is unknown. Additional, whether a relationship exists between the respiratory tract and gut antibiotic resistance genes composition has not been fully explored. Method We recruited 66 patients with COVID-19 at three disease stages (admission, progression and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Results Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrugand Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin and Fosmidomycinwere increased in ICU patients. Upon further investigation a significantly positive correlation was found between the relative abundance in ARGs (i.e., subtypes of the Aminoglycoside and Tetracyclinetypes) in the respiratory tract and gut. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in respiratory tract and gut. We found that immune related pathways in PBMC were enhanced, and they were significantly correlated with the relative abundance of Multidrug, Vancomycin and Tetracycline ARGs. Based on the relative abundance of ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. The level of Aminoglycoside and Vancomycinin the gut was regarded as the most prominent biomarker. Conclusions Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

How Knowledge Sharing Affects Business Model Innovation: An Empirical Study from the Perspective of Ambidextrous Organizational Learning

In the era of knowledge economy and open innovation, it is especially important for organizations to learn how to store and utilize internal and external knowledge for the sustainability of business models. The ability to innovate is a necessity for sustainable development, thus this paper starting from the internal factors driving enterprises to realize business model innovation, from perspective of ambidextrous organizational learning, takes 257 managers in enterprises as samples to empirically study the mechanism of knowledge sharing on business model innovation. The results of regression analysis and structural equation model (SEM) path analysis show that knowledge sharing affects novel and efficient business model innovation through ambidextrous organizational learning, and ambidextrous organizational learning plays a complete mediating role. Both explorative and exploitative learning have a significant positive impact on the novel and efficient business model innovation, and explorative learning has a stronger promoting effect. Therefore, in the practice of enterprise business model innovation, leaders need to establish a system that can promote the willingness of employees to share knowledge. Organizations need to pay attention to the effectiveness of explorative learning, consider the actual demand of employees as much as possible, and mobilize the initiative of employees in the learning process. Organizations also are required to pay attention to the balance between explorative learning and exploitative learning.

Analysis of Continuous Mutation and Evolution on Circulating SARS-CoV-2

Monitoring the mutation and evolution of the virus is important for tracing its ongoing transmission and facilitating effective vaccine development. A total of 342 complete genomic sequences of SARS-CoV-2 were analyzed in this study. Compared to the reference genome reported in December 2019, 465 mutations were found, among which, 347 occurred in only 1 sequence, while 26 occurred in more than 5 sequences. For these 26 further identified as SNPs, 14 were closely linked and were grouped into 5 profiles. Phylogenetic analysis revealed the sequences formed 2 major groups. Most of the sequences in late period (March and April) constituted the Cluster II, while the sequences before March in this study and the reported S/L and A/B/C types in previous studies were all in Cluster I. The distributions of some mutations were specific geographically or temporally, the potential effect of which on the transmission and pathogenicity of SARS-CoV-2 deserves further evaluation and monitoring. Two mutations were found in the receptor-binding domain (RBD) but outside the receptor-binding motif (RBM), indicating that mutations may only have marginal biological effects but merit further attention. The observed novel sequence divergence is of great significance to the study of the transmission, pathogenicity, and development of an effective vaccine for SARS-CoV-2.

Priority Weights for Predicting the Success of Hotel Sustainable Business Models

This study proposes the use of consistent fuzzy preference relations to evaluate the structure of hotel sustainable business model (HSBM) dimensions and the corresponding hierarchy of evaluation indicators, and predict the overall probability of success. As fuzzy preference relations require, a group of hotel professionals in Taiwan was asked to process pairwise comparisons using linguistic variables to determine the weights of dimensions and indicators. According to the results, finances were found to be the most important dimension, followed by human capital. The number of local cultural events in the hotel was identified as the most important indicator. The predictive values revealed the possibility for successful HSBM implementation, shedding light on the vision of sustainability for the hotel industry. The results of the present study contribute to the literature on sustainability by determining the importance and weights of dimensions and indicators for hotel business models, providing an example of the use of this strategic tool in generating and modifying sustainable business models for the hotel industry.

Clinical performance characteristics of the Swift Normalase Amplicon Panel for sensitive recovery of SARS-CoV-2 genomes (preprint)

Amplicon-based sequencing methods have been central in characterizing the diversity, transmission and evolution of SARS-CoV-2, but need to be rigorously assessed for clinical utility. Here, we validated the Swift Biosciences SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens with a 95% limit of detection of 40.08 SARS-CoV-2 copies/PCR reaction. Breadth of genome recovery was evaluated across a range of Ct values (11.3 - 36.7, median 21.6). Out of 428 positive samples, 406 (94.9%) generated genomes with < 10% Ns, with a mean genome coverage of 13,545X/SD 8,382X. No genomes were recovered from PCR-negative specimens (n = 30), or from specimens positive for non-SARS-CoV-2 respiratory viruses (n = 20). Compared to whole-genome shotgun metagenomic sequencing (n = 14) or Sanger sequencing for the spike gene (n = 11), pairwise identity between consensus sequences was 100% in all cases, with highly concordant allele frequencies (R2 = 0.99) between Swift and shotgun libraries. When samples from different clades were mixed at varying ratios, expected variants were detected even in 1:99 mixtures. When deployed as a clinical test, 268 tests were performed in the first 23 weeks with a median turnaround time of 11 days, ordered primarily for outbreak investigations and infection control.

Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants. (preprint)

BackgroundNovel SARS-CoV-2 Variants of Concern (VoC) pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between viral RNA and infectious virus for individual variants is unknown. MethodsWe measured infectious viral titer (using a micro-focus forming assay) as well as total and subgenomic viral RNA levels (using RT-PCR) in a set of 165 clinical samples containing SARS-CoV-2 Alpha, Delta and Epsilon variants that were processed within two days of collection from the patient. ResultsWe observed a high degree of variation in the relationship between viral titers and RNA levels. Despite the variability we observed for individual samples the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (6 and 4 times as much, p=0.0002 and 0.009 respectively) or subgenomic E RNA (11 and 7 times as much, p<0.0001 and 0.006 respectively). ConclusionIn addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may also be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity of the Delta variant may further explain increased spread and suggests a need for increased measures to prevent viral transmission. SIGNIFICANCE STATEMENTCurrent and future SARS-CoV-2 variants threaten our ability to control the COVID-19 pandemic. Variants with increased transmission, higher viral loads, or greater immune evasion are of particular concern. Viral loads are currently measured by the amount of viral RNA in a clinical sample rather than the amount of infectious virus. We measured both RNA and infectious virus levels directly in a set of 165 clinical specimens from Alpha, Epsilon or Delta variants. Our data shows that Delta is more infectious compared to Alpha, with [~] six times as much infectious virus for the same amount of RNA. This increase in infectivity suggests increased measures (vaccination, masking, distancing, ventilation) are needed to control Delta compared to Alpha.

Predicting Infectivity: Comparing Four PCR-based Assays to Detect Culturable SARS-CoV-2 in Clinical Samples (preprint)

ABSTRACT With the COVID-19 pandemic caused by SARS-CoV-2 now in its second year, there remains an urgent need for diagnostic testing that can identify infected individuals, particularly those who harbor infectious virus. Various RT-PCR strategies have been proposed to identify specific viral RNA species that may predict the presence of infectious virus, including detection of transcriptional intermediates (e.g. subgenomic RNA [sgRNA]) and replicative intermediates (e.g. negative-strand RNA species). Using a novel primer/probe set for detection of subgenomic (sg)E transcripts, we successfully identified 100% of specimens containing culturable SARS-CoV-2 from a set of 126 clinical samples (total sgE C T values ranging from 12.3-37.5). This assay showed superior performance compared to a previously published sgRNA assay and to a negative-strand RNA assay, both of which failed to detect target RNA in a subset of samples from which we isolated live virus. In addition, total levels of viral RNA (genome, negative-strand, and sgE) detected with the WHO/Charité primer-probe set correlated closely with levels of infectious virus. Specifically, infectious virus was not detected in samples with a C T above 31.0. Clinical samples with higher levels of viral RNA also displayed cytopathic effect (CPE) more quickly than those with lower levels of viral RNA. Finally, we found that the infectivity of SARS-CoV-2 samples is significantly dependent on the cell type used for viral isolation, as Vero E6 cells expressing TMRPSS2 extended the analytical sensitivity of isolation by more than 3 C T compared to parental Vero E6 cells and resulted in faster isolation. Our work shows that using a total viral RNA Ct cut-off of >31 or specifically testing for sgRNA can serve as an effective rule-out test for viral infectivity.

Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State (preprint)

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Anti-SARS-CoV-2 antibody levels are concordant across multiple platforms but are not fully predictive of sterilizing immunity (preprint)

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-spike serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA authorized semi-quantitative anti-spike AdviseDx SARS-CoV-2 IgG II assay compared to the FDA authorized anti-nucleocapsid Abbott Architect SARS-CoV-2 IgG, Roche elecsys Anti-SARS-CoV-2-S, EuroImmun Anti-SARS-CoV-2 ELISA, and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and breakthrough infection. The AdviseDx assay had a clinical sensitivity at 14 days post-symptom onset or 10 days post PCR detection of 95.6% (65/68, 95% CI: 87.8-98.8%) with two discrepant individuals seroconverting shortly thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four other assays examined using the same symptom onset or PCR detection cutoffs. Using a recently available WHO International Standard for anti-SARS-CoV-2 antibody, we provide assay unit conversion factors to international units for each of the assays examined. We performed a longitudinal survey of healthy vaccinated individuals, finding median AdviseDx immunoglobulin levels peaked seven weeks post-first vaccine dose at approximately 4,000 IU/mL. Intriguingly, among the five assays examined, there was no significant difference in antigen binding level or neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection in a previously described fishing vessel outbreak and five healthcare workers who experienced vaccine breakthrough of SARS-CoV-2 infection, all with variants of concern. These findings suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively using in vitro antibody assays against wildtype SARS-CoV-2 spike. Further work is required to establish protective correlates of protection for SARS-CoV-2 infection.

An international, inter-laboratory ring trial confirms the feasibility of an open source, extraction-less "direct" RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples (preprint)

RT-qPCR is used world-wide to test and trace the spread of SARS-CoV-2. Extraction-less or direct RT-PCR is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal (NP) or oral pharyngeal (OP) samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged ten global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international inter-laboratory ring trial. Participating labs were provided a common protocol, common reagents, aliquots of identical pooled clinical samples and purified nucleic acids, and used their existing in-house equipment. We observed 100% concordance across labs in the correct identification of all positive and negative samples, with highly similar Ct values observed. The test also performed well when applied to locally collected patient NP samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that open access, direct RT-PCR assays are a feasible option for more efficient COVID-19 testing as demanded by the continuing pandemic.

Phylogenetic estimates of SARS-CoV-2 introductions into Washington State (preprint)

Background: The first confirmed case of SARS-CoV-2 in North America was identified in Washington state on January 21, 2020. We aimed to quantify the number and temporal trends of out-of-state introductions of SARS-CoV-2 into Washington. Methods: We conducted a phylogenetic analysis of 11,422 publicly available whole genome SARS-CoV-2 sequences from GISAID sampled between December 2019 and September 2020. We used maximum parsimony ancestral state reconstruction methods on time-calibrated phylogenies to enumerate introductions/exports, their likely geographic source (e.g. US, non-US, and between eastern and western Washington), and estimated date of introduction. To incorporate phylogenetic uncertainty into our estimates, we conducted 5,000 replicate analyses by generating 25 random time-stratified samples of non-Washington reference sequences, 20 random polytomy resolutions, and 10 random resolutions of the reconstructed ancestral state. Results: We estimated a minimum 287 separate introductions (median, range 244-320) into Washington and 204 exported lineages (range 188-227) of SARS-CoV-2 out of Washington. Introductions began in mid-January and peaked on March 29, 2020. Lineages with the Spike D614G variant accounted for the majority (88%) of introductions. Overall, 61% (range 55-65%) of introductions into Washington likely originated from a source elsewhere within the US, while the remaining 39% (range 35-45%) likely originated from outside of the US. Intra-state transmission accounted for 65% and 28% of introductions into eastern and western Washington, respectively. Conclusions: There is phylogenetic evidence that the SARS-CoV-2 epidemic in Washington is continually seeded by a large number of introductions, and that there was significant inter- and intra-state transmission. Due to incomplete sampling our data underestimate the true number of introductions.

Optimal parameterization of COVID-19 epidemic models

ABSTRACT At the time of writing, coronavirus disease 2019 (COVID-19) is seriously threatening human lives and health throughout the world. Many epidemic models have been developed to provide references for decision-making by governments and the World Health Organization. To capture and understand the characteristics of the epidemic trend, parameter optimization algorithms are needed to obtain model parameters. In this study, the authors propose using the Levenberg–Marquardt algorithm (LMA) to identify epidemic models. This algorithm combines the advantage of the Gauss–Newton method and gradient descent method and has improved the stability of parameters. The authors selected four countries with relatively high numbers of confirmed cases to verify the advantages of the Levenberg–Marquardt algorithm over the traditional epidemiological model method. The results show that the Statistical-SIR (Statistical-Susceptible–Infected–Recovered) model using LMA can fit the actual curve of the epidemic well, while the epidemic simulation of the traditional model evolves too fast and the peak value is too high to reflect the real situation. 摘要 现如今, 新冠肺炎(COVID-19)严重威胁着世界各国人民的生命健康.许多流行病学模型已经被用于为政策制定者和世界卫生组织提供决策参考.为了更加深刻的理解疫情趋势的变化特征, 许多参数优化算法被用于反演模型参数.本文提议使用结合了高斯-牛顿法和梯度下降法的Levenberg–Marquardt(LMA)算法来优化模型参数.使用四个病例数相对较多的国家来验证这一算法的优势:相较于传统流行病学模型模拟曲线过早过快的到达峰值, 应用LMA的Statistical-SIR(Statistical-Susceptible–Infected–Recovered)模型可以更好地拟合实际疫情曲线.

Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial (preprint)

Background: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission.Methods: In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent control trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive HCQ (400mg BID x1day, followed by 200mg BID x9days) or placebo-equivalent (ascorbic acid) and AZ (500mg, then 250mg daily x4days) or placebo-equivalent (folic acid), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected mid-turbinate nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility.Findings: Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Incident LRTI occurred in six participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in nine (four control, two HCQ, three HCQ/AZ). There were no deaths. Median time to clearance was 5 days (95% CI=4-6) in HCQ, 6 days (95% CI=4-8) in HCQ/AZ, and 8 days (95% CI=6-10) in control. HCQ but not HCQ/AZ had faster time to viral clearance (HR=1.62, 95% CI=1.01-2.60, p=0.047 & HR=1.25, 95% CI=0.75-2.07, p=0.39) compared to control. Among 197 participants who met the COVID-19 definition at enrollment, time to symptom resolution did not differ by group.Interpretation: Neither HCQ nor HCQ/AZ shortened the clinical course of outpatients with COVID-19, and HCQ, but not HCQ/AZ, had only a modest effect on SARS-CoV-2 viral shedding. HCQ and HCQ/AZ are not effective therapies for outpatient treatment of SARV-CoV-2 infection.Trial Registration Number: ClinicalTrials.gov: NCT04354428Funding: The COVID-19 Early Treatment Study was funded by the Bill & Melinda Gates Foundation (INV-017062) through the COVID-19 Therapeutics Accelerator. University of Washington Institute of Translational Health Science (ITHS) grant support (UL1 TR002319), KL2 TR002317, and TL1 TR002318 from NCATS/NIH funded REDCap. The content is solely the responsibility of the authors and does not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. PAN and MJA were supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Conflict of Interest: Declaration of interests: CJ reports grants from BMGF for conduct of the study, and grants from CDC and NIH outside of the submitted work. HSK reports funding from NIH. PAN and MJA have a potential financial relationship with AliveCor related to QT assessment using the device, however the investigators would receive no financial benefit for use of the technology for patients at Mayo Clinic or for its use in the current study. AB reports consulting for Gates Ventures and grants from BMGF and NIH outside of the submitted work. HYC reports consulting for BMGF, Pfizer, Ellume, and Merck, and grants from Gates Ventures, NIH, CDC, BMGF, DARPA, Apple Inc., Sanofi-Pasteur, and Roche-Genentech, outside of the submitted work. Ethical Approval: Study visits were conducted via Health Insurance Portability and Accountability Act (HIPAA)-compliant telemedicine. The Western Institutional Review Board (WIRB) approved this study with reliance agreements with collaborating institutions.

Vulnerability of Young Children with COVID-19: Impacts of ACE2 Expression Patterns and Lung Progenitor Cells on Infants (preprint)

Background: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin- converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 25, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children’s lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Findings: It revealed that infants (<1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (>1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children’s lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants’ lungs. The ACE2+ SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Interpretation: Infants (<1 yrs.-old) with COVID-19 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from COVID-19 infection. Funding: National Natural Science Grant of China (No 31571407; 31970910); Hong Kong Health and Medical Research Fund (HMRF) (No:06172956), and Stem Cell and Regenerative Medicine Fund (Guangzhou Women and Children's Medical Centre, Grant No:5001-4001010)Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the respective Institutional Review Board. Written informed consent was obtained from patients and/or guardians before data collected.

Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State (preprint)

The rapid spread of SARS-CoV-2 has gravely impacted societies around the world. Outbreaks in different parts of the globe are shaped by repeated introductions of new lineages and subsequent local transmission of those lineages. Here, we sequenced 3940 SARS-CoV-2 viral genomes from Washington State to characterize how the spread of SARS-CoV-2 in Washington State (USA) was shaped by differences in timing of mitigation strategies across counties, as well as by repeated introductions of viral lineages into the state. Additionally, we show that the increase in frequency of a potentially more transmissible viral variant (614G) over time can potentially be explained by regional mobility differences and multiple introductions of 614G, but not the other variant (614D) into the state. At an individual level, we see evidence of higher viral loads in patients infected with the 614G variant. However, using clinical records data, we do not find any evidence that the 614G variant impacts clinical severity or patient outcomes. Overall, this suggests that at least to date, the behavior of individuals has been more important in shaping the course of the pandemic than changes in the virus.

Individualism and the Fight against COVID-19 (preprint)

We demonstrate that COVID-19 displays a spatial discontinuity along the former East-West German border and German virus-fighting policies are more effective in former pro-state and pro-collectivism East German districts. In an international setting using the number of Nobel-Prize winners as an instrument, we show that individualism aggravates the severity of COVID-19 through reducing the effectiveness of social distancing and mobility restriction policies. We conclude that individualism potentially impedes the containment of COVID-19. A greater reluctance among people in more individualistic cultures to heed virus-fighting policies can potentially impose a negative public health externality during a pandemic.

Identification of multiple large deletions in ORF7a resulting in in-frame gene fusions in clinical SARS-CoV-2 isolates (preprint)

Peculiar among human RNA viruses, coronaviruses have large genomes containing accessory genes that are not required for replication. Numerous mutations within the SARS-CoV-2 genome have been described but few deletions in the accessory genes of SARS-CoV-2 have been reported. Here, we report two large deletions in ORF7a, both of which produce new open reading frames (ORFs) through the fusion of the N-terminus of ORF7a and a downstream ORF.