Low Prevalence but High Impact of COVID-19 Positive Status in Adult Trauma Patients: A Multi-institutional Analysis of 28 904 Patients.

BACKGROUND: Few large investigations have addressed the prevalence of COVID-19 infection among trauma patients and impact on providers. The purpose of this study was to quantify the prevalence of COVID-19 infection among trauma patients by timing of diagnosis, assess nosocomial exposure risk, and evaluate the impact of COVID-19 positive status on morbidity and mortality. METHODS: Registry data from adults admitted 4/1/2020-10/31/2020 from 46 level I/II trauma centers were grouped by: timing of first positive status (Day 1, Day 2-6, or Day ≥ 7); overall Positive/Negative status; or Unknown if test results were unavailable. Groups were compared on outcomes (Trauma Quality Improvement Program complications) and mortality using univariate analysis and adjusted logistic regression. RESULTS: There were 28 904 patients (60.7% male, mean age: 56.4, mean injury severity score: 10.5). Of 13 274 (46%) patients with known COVID-19 status, 266 (2%) were Positive Day 1, 119 (1%) Days 2-6, 33 (.2%) Day ≥ 7, and 12 856 (97%) tested Negative. COVID-19 Positive patients had significantly worse outcomes compared to Negative; unadjusted comparisons showed longer hospital length of stay (10.98 vs 7.47;P < .05), higher rates of intensive care unit (57.7% vs 45.7%; P < .05) and ventilation use (22.5% vs 16.9%; P < .05). Adjusted comparisons showed higher rates of acute respiratory distress syndrome (1.7% vs .4%; P < .05) and death (8.1% vs 3.4%; P < .05). CONCLUSIONS: This multicenter study conducted during the early pandemic period revealed few trauma patients tested COVID-19 positive, suggesting relatively low exposure risk to care providers. COVID-19 positive status was associated with significantly higher mortality and specific morbidity. Further analysis is needed with consideration for care guidelines specific to COVID-19 positive trauma patients as the pandemic continues.

IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.

An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

The effect of perceived organizational support on the prohibitive voice behavior of knowledgeable talents during the COVID-19 pandemic: Exploring moderating role of the digitalization level.

This study focuses on the effect of perceived organizational support on the prohibitive voice of knowledgeable talents and on the factors influencing that voice during the COVID-19 pandemic in China. Grounding our research in social exchange theory and the Chinese sociocultural background, we collected data from 714 questionnaires from universities in Zhejiang Province and analysize by linear regression and found, first, that perceived organizational support significantly increased the prohibitive voice of knowledgeable talents and, second, that in the relationship between perceived organizational support and the prohibitive voice of those talents, the level of digitalization level of an organization has a positive the effect of perceived organizational support on prohibitive voice behavior. This study enriches the theory of voice behavior, helps universities understand the behavioral patterns of knowledgeable talents and guides the cultivation of an atmosphere with prohibitive voice behavior.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

Equilibrative Nucleoside Transporter 3 is an IFN-stimulated Gene that Facilitates Viral Genome Release (preprint)

An increasing body of evidence emphasizes the role of metabolic reprogramming in immune cells to fight off infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that equilibrative nucleoside transporter 3 (ENT3) expression is part of the innate immune response, and is rapidly upregulated upon bacterial and viral infection. The transcription of ENT3 is directly under the regulation of IFN-induced signaling, positioning this metabolite transporter as an Interferon-stimulated gene (ISG). Moreover, we unveil that several viruses, including SARS-CoV2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of ENT3 expression is sufficient to significantly decrease viral replication in vitro and in vivo.

Rain Classroom assisted by WeChat for preliminary online physiology teaching during the COVID-19 pandemic.

Due to the COVID-19 pandemic during spring semester 2020, teachers and students were forced to engage in online instruction. However, there is little evidence on the feasibility of online physiology teaching. This study demonstrated a 3-wk preliminary online physiology course based on Rain Classroom assisted by the mobile application WeChat. Eighty-seven nursing undergraduate students attended an online physiology course during the spring semester of the 2019-2020 academic year from March 9 to March 29. We determined the effects of the online physiology learning based on in-class tests, preclass preparation, and review rates for the course materials. We also measured the students' perceptions and attitudes about online learning with a questionnaire survey. Posttest scores from the first week to the third week in online physiology course (7.22 ± 1.83, 7.68 ± 2.09, and 6.21 ± 2.92, respectively) exceeded the pretest scores (5.32 ± 2.14, 6.26 ± 2.49, and 3.72 ± 2.22, respectively), and this finding was statistically significant (all P < 0.001). Moreover, the pretest scores were significant positive predictors of final grade (all P < 0.01). In addition, the percentage of preclass preparation increased in 3 wk, from 43.68% to 57.47% to 68.97%. From the first week to the third week, the review rate increased from 86.21% to 91.95%; however, the second week was the lowest of all (72.41%). Finally, students' perceptions about their online physiology learning experiences were favorable. In conclusion, online physiology instruction based on Rain Classroom assisted by WeChat was an effective strategy during the COVID-19 pandemic.

Discontinuation of atorvastatin use in hospital is associated with increased risk of mortality in COVID-19 patients.

BACKGROUND: Statins are a commonly used class of drugs, and reports have suggested that their use may affect COVID-19 disease severity and mortality risk. OBJECTIVE: The purpose of this analysis was to determine the effect of discontinuation of previous atorvastatin therapy in patients hospitalized for COVID-19 on the risk of mortality and ventilation. METHODS: Data from 146,413 hospitalized COVID-19 patients were classified according to statin therapy. Home + in hospital atorvastatin use (continuation of therapy); home + no in hospital atorvastatin use (discontinuation of therapy); no home + no in hospital atorvastatin use (no statins). Logistic regression was performed to assess the association between atorvastatin administration and either mortality or use of mechanical ventilation during the encounter. RESULTS: Continuous use of atorvastatin (home and in hospital) was associated with a 35% reduction in the odds of mortality compared to patients who received atorvastatin at home but not in hospital (odds ratio [OR]: 0.65, 95% confidence interval [CI]: 0.59-0.72, p < .001). Similarly, the odds of ventilation were lower with continuous atorvastatin therapy (OR: 0.70, 95% CI: 0.64-0.77, p < .001). CONCLUSIONS: Discontinuation of previous atorvastatin therapy is associated with worse outcomes for COVID-19 patients. Providers should consider maintaining existing statin therapy for patients with known or suspected previous use.

Novel nanostructure-coupled biosensor platform for one-step high-throughput quantification of serum neutralizing antibody after COVID-19 vaccination.

COVID-19 vaccination efficacy depends on serum levels of the neutralizing antibodies (NAs) specific to the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Therefore, a high-throughput rapid assay capable of measuring the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a novel nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.2 pM within 15 min without washing steps. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable with those obtained in the gold-standard seroneutralization test and the surrogate virus-neutralizing enzyme-linked immunosorbent assay. Collectively, the one-step NanoPISA might be a rapid and high-throughput NA-quantification platform for evaluating the effectiveness of COVID-19 vaccines.

Impact of Monetary Policy Uncertainty on R&D Investment Smoothing Behavior of Pharmaceutical Manufacturing Enterprises: Empirical Research Based on a Threshold Regression Model.

R&D investment is the source of technological innovation of pharmaceutical enterprises, but it will be restricted by the funding level, especially in the context of major public health emergencies occurring more frequently, therefore exploring the impact of monetary policy uncertainty on the R&D investment smoothing behavior of pharmaceutical manufacturing enterprises has important theoretical and practical value. Based on the relevant data of Chinese pharmaceutical manufacturing enterprises from 2012 to 2018, this paper studies the impact of monetary policy uncertainty on R&D investment smoothing behavior of pharmaceutical enterprises, and investigates whether there is a threshold effect. First, our results demonstrate that the empirical test results of this article support the hypothesis of R&D investment smoothing behavior of pharmaceutical manufacturing enterprises. Second, there is a negative correlation between monetary policy uncertainty and R&D investment smoothing behavior, and the shorter the period is, the higher the financing constraints of pharmaceutical enterprises are, and the more obvious the negative correlation is. Third, financing constraints have a single threshold effect on the R&D investment smoothing behavior of pharmaceutical manufacturing enterprises, with a threshold of -13.7693. Moreover, this conclusion can better promote the virtuous circle of the real economy of financial and pharmaceutical manufacturing enterprises. It is recommended that pharmaceutical manufacturing enterprises establish and improve the enterprise R&D reserve system, reduce the risk of R&D investment, play the role of R&D smoothing, and realize the sustainable development of enterprise R&D.

Infection mechanism of SARS-CoV-2 and its control of transmission route

SARS-CoV-2 virus is the pathogen of COVID-19, its intermediate host, infection mechanism and transmission route need to be further studied and verified. In this study, we analyzed the mechanism of SARS-Co V-2 infecting the host, discussed the infection path and infection media of SARS-CoV-2, and put forward effective measures to control the spread of SARS-CoV-2, and we took the first unknown pneumonia case received by Doctor Zhang Jixian, a director of the Department of Infectious Diseases of Hubei Provincial Hospital of Chinese& Western Medicine as an example, illustrating how to carry out professional medical treatment and control according to professional regulations and laws and regulations, which we try to provide scientific basis for effectively controlling the virus transmission and spread of infectious diseases and quickly placing it under the control of the government and health institutions.

Decreased adult trauma admission volumes and changing injury patterns during the COVID-19 pandemic at 85 trauma centers in a multistate healthcare system.

BACKGROUND: Reports indicate social distancing guidelines and other effects of the COVID-19 pandemic impacted trauma patient volumes and injury patterns. This report is the first analysis of a large trauma network describing the extent of these impacts. The objective of this study was to describe the effects of the COVID-19 pandemic on patient volumes, demographics, injury characteristics, and outcomes. METHODS: For this descriptive, multicenter study from a large, multistate hospital network, data were collected from the system-wide centralized trauma registry and retrospectively reviewed to retrieve patient information including volume, demographics, and outcomes. For comparison, patient data from January through May of 2020 and January through May of 2019 were extracted. RESULTS: A total of 12 395 trauma patients (56% men, 79% white, mean age 59 years) from 85 trauma centers were included. The first 5 months of 2020 revealed a substantial decrease in volume, which began in February and continued into June. Further analysis revealed an absolute decrease of 32.5% in patient volume in April 2020 compared with April 2019 (4997 from 7398; p<0.0001). Motor vehicle collisions decreased 49.7% (628 from 1249). There was a statistically significant increase in injury severity score (9.0 vs. 8.3; p<0.001). As a proportion of the total trauma population, blunt injuries decreased 3.1% (87.3 from 90.5) and penetrating injuries increased 2.7% (10.0 from 7.3; p<0.001). A significant increase was found in the proportion of patients who did not survive to discharge (3.6% vs. 2.8%; p=0.010; absolute decrease: 181 from 207). DISCUSSION: Early phases of the COVID-19 pandemic were associated with a 32.5% decrease in trauma patient volumes and altered injury patterns at 85 trauma centers in a multistate system. This preliminary observational study describes the initial impact of the COVID-19 pandemic and warrants further investigation. LEVEL OF EVIDENCE: Level II (therapeutic/care management).

Differential diagnosis and prospective grading of COVID-19 at the early stage with simple hematological and biochemical variables.

We evaluated simple laboratory variables to discriminate COVID-19 from bacterial pneumonia or influenza and for the prospective grading of COVID-19. Multivariate logistic regression and receiver operating characteristic curve were used to estimate the diagnostic performance of the significant discriminating variables. A comparative analysis was performed with different severity. The leukocytosis (P = 0.017) and eosinopenia (P = 0.001) were discriminating variables between COVID-19 and bacterial pneumonia with area under the curve (AUC) of 0.778 and 0.825. Monocytosis (P = 0.003), the decreased lymphocyte-to-monocyte ratio (P < 0.001), and the increased neutrophil-to-lymphocyte ratio (NLR) (P = 0.028) were predictive of influenza with AUC of 0.723, 0.895, and 0.783, respectively. Serum amyloid protein, lactate dehydrogenase, CD3+ cells, and the fibrinogen degradation products had a good correlation with the severity of COVID-19 graded by age (≥50) and NLR (≥3.13). Simple laboratory variables are helpful for rapid diagnosis on admission and hierarchical management of COVID-19 patients.

Characteristics of pediatric multi-system inflammatory syndrome (PMIS) associated with COVID-19: a meta-analysis and insights into pathogenesis.

OBJECTIVES: There was an outbreak of pediatric multisystem inflammation syndrome (PMIS) was observed in multiple countries recently, and this syndrome was suspected to be associated with SARS-CoV-2 infection. At present, there is still no standardized diagnostic criteria and treatment regimen for PMIS, while the etiology and pathogenesis still remain unclear. METHODS: We performed a systematic review on PubMed and Embase from the time of inception to June 24th 2020 in order to find relevant cases. RESULTS: There are seven studies included, and 80% of patients suffered persistent fever and 90% appeared gastrointestinal symptoms. IgG antibody against SARS-CoV-2 was positive on 81% of patients, while 37% of the patients were nucleic acid positive. C-reactive protein, IL-6 and PCT were elevated and intravenous immunoglobulin was a routine treatment for PMIS. There were more than half of patients required inotropic supports and mechanical ventilation were applied to 33% of patients. The median length of hospital stay was 10.66 days and 74% had admitted to accept intensive care. CONCLUSIONS: Our study documented three common types of PMIS clinical presentation: persistent fever and gastrointestinal symptoms, shocked with heart dysfunction and Kawasaki disease-like syndrome. PMIS patients proved with a marked inflammatory state were possibly associated with SARS-CoV-2 infection.