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1.
Front Microbiol ; 12: 747347, 2021.
Article in English | MEDLINE | ID: covidwho-1528834

ABSTRACT

Sex hormones are steroid hormones synthesized from the gonads of animals and tissues such as the placenta and adrenocortical reticular zone. The physiological functions of sex hormones are complex. Sex hormones are not only pathologically correlated with many diseases of the reproductive system, but are etiological factors in some viral infectious diseases, including disease caused by infections of coronaviruses, herpesviruses, hepatitis viruses, and other kinds of human viruses, which either exhibit a male propensity in clinical practice, or crosstalk with androgen receptor (AR)-related pathways in viral pathogenesis. Due to the global pandemic of coronavirus disease 2019 (COVID-19), the role of androgen/AR in viral infectious disease is highlighted again, majorly representing by the recent advances of AR-responsive gene of transmembrane protease/serine subfamily member 2 (TMPRSS2), which proteolytically activates the receptor-mediated virus entry by many coronaviruses and influenza virus, along with the role of androgen-mediated signaling for the transcription of hepatitis B virus (HBV), and the role of sex hormone responsive genes during Zika virus (ZIKV) pathogenesis, et al. Collectively, we propose to provide a comprehensive overview of the role of male sex hormones during multiple phases in the life cycle of different human viruses, which may be partly responsible for the sex-specific prevalence, severity and mortality of some diseases, therefore, may provide clues to develop more efficient prevention and treatment strategies for high-risk populations.

2.
Int J Infect Dis ; 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1517207

ABSTRACT

OBJECTIVES: The exact characteristics of a COVID-19 outbreak that trigger public health interventions are poorly defined. We aimed to assess the critical timing and extent of public health interventions to contain COVID-19 outbreaks in Australia. METHODS: We developed a practical model using existing epidemics data in Australia. We quantified the effective combinations of public health interventions and the critical number of daily cases for intervention commencement under various scenarios of changes in transmissibility of new variants and vaccination coverage. RESULTS: In the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wildtype-dominant epidemic to a low level (≤10 cases/day) required effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches 6 cases. Containing an Alpha-dominant epidemic would require more stringent interventions that commenced earlier. For Delta variant, public health interventions alone will not contain the epidemic unless with vaccination coverage of ≥70%. CONCLUSIONS: Our study highlights the importance of early and decisive action in the initial phase of an outbreak. Vaccination is essential for containing variants.

3.
Sensors ; 21(22):7540, 2021.
Article in English | MDPI | ID: covidwho-1512573

ABSTRACT

Existing wearable systems that use G-sensors to identify daily activities have been widely applied for medical, sports and military applications, while body temperature as an obvious physical characteristic that has rarely been considered in the system design and relative applications of HAR. In the context of the normalization of COVID-19, the prevention and control of the epidemic has become a top priority. Temperature monitoring plays an important role in the preliminary screening of the population for fever. Therefore, this paper proposes a wearable device embedded with inertial and temperature sensors that is used to apply human behavior recognition (HAR) to body surface temperature detection for body temperature monitoring and adjustment by evaluating recognition algorithms. The sensing system consists of an STM 32-based microcontroller, a 6-axis (accelerometer and gyroscope) sensor, and a temperature sensor to capture the original data from 10 individual participants under 4 different daily activity scenarios. Then, the collected raw data are pre-processed by signal standardization, data stacking and resampling. For HAR, several machine learning (ML) and deep learning (DL) algorithms are implemented to classify the activities. To compare the performance of different classifiers on the seven-dimensional dataset with temperature sensing signals, evaluation metrics and the algorithm running time are considered, and random forest (RF) is found to be the best-performing classifier with 88.78% recognition accuracy, which is higher than the case of the absence of temperature data (<78%). In addition, the experimental results show that participants’ body surface temperature in dynamic activities was lower compared to sitting, which can be associated with the possible missing fever population due to temperature deviations in COVID-19 prevention. According to different individual activities, epidemic prevention workers are supposed to infer the corresponding standard normal body temperature of a patient by referring to the specific values of the mean expectation and variance in the normal distribution curve provided in this paper.

4.
Signal Transduct Target Ther ; 6(1): 387, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1510581

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). To halt the pandemic, multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide. With novel SARS-CoV-2 variants emerging and circulating widely, whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion. Moreover, some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity. Thus, in this review, we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern. We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials. Furthermore, we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines, such as special disease conditions, sex, and pre-existing immunity, with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Humans , Immunogenicity, Vaccine , Pandemics , SARS-CoV-2/genetics , Vaccination
5.
Results Phys ; 31: 104971, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1510269

ABSTRACT

The coronavirus infectious disease (COVID-19) is a novel respiratory disease reported in 2019 in China. The COVID-19 is one of the deadliest pandemics in history due to its high mortality rate in a short period. Many approaches have been adopted for disease minimization and eradication. In this paper, we studied the impact of various constant and time-dependent variable control measures coupled with vaccination on the dynamics of COVID-19. The optimal control theory is used to optimize the model and set an effective control intervention for the infection. Initially, we formulate the mathematical epidemic model for the COVID-19 without variable controls. The model basic mathematical assessment is presented. The nonlinear least-square procedure is utilized to parameterize the model from actual cases reported in Pakistan. A well-known technique based on statistical tools known as the Latin-hypercube sampling approach (LHS) coupled with the partial rank correlation coefficient (PRCC) is applied to present the model global sensitivity analysis. Based on global sensitivity analysis, the COVID-19 vaccine model is reformulated to obtain a control problem by introducing three time dependent control variables for isolation, vaccine efficacy and treatment enhancement represented by u 1 ( t ) , u 2 ( t ) and u 3 ( t ) , respectively. The necessary optimality conditions of the control problem are derived via the optimal control theory. Finally, the simulation results are depicted with and without variable controls using the well-known Runge-Kutta numerical scheme. The simulation results revealed that time-dependent control measures play a vital role in disease eradication.

6.
Chinese Journal of School Health ; 42(5):697-701, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1502919

ABSTRACT

Objective: To explore the characteristics and relationship between physical activity and self-efficacy of college students during the COVID-19 epidemic, so as to provide evidence for the orderly development of physical education and curriculum reform of college students after their return to school.

7.
Wireless Blockchain ; : 225-243, 2021.
Article in English | Wiley | ID: covidwho-1487431

ABSTRACT

Summary In light of the fast-spreading number of COVID-19 cases worldwide, contact tracing proved to be an effective measure to slow down the infection rate and mitigate the casualties caused by this virus. However, because of several concerns in terms of privacy, as well as security, several countries and their population around the globe are reluctant to adopt contact tracing solutions to contain the spread of the virus. Because of its distributed, public, and auditable nature, blockchain can be a groundbreaking solution contact tracing, given that it would provide a privacy-oriented contact tracing solution. Therefore, in this chapter, we discuss and compare the two alternatives proposed by the BeepTrace framework, active and passive, and also present some initial results based on an early implementation of it. As it can be seen, by utilizing blockchain together with contact tracing, user privacy, security, and decentralization can be guaranteed, giving back the trust needed for these applications to work.

8.
BMJ Open ; 11(10): e052823, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462970

ABSTRACT

OBJECTIVES: The incidence of Neisseria gonorrhoeae and its antimicrobial resistance is increasing in many countries. Antibacterial mouthwash may reduce gonorrhoea transmission without using antibiotics. We modelled the effect that antiseptic mouthwash may have on the incidence of gonorrhoea. DESIGN: We developed a mathematical model of the transmission of gonorrhoea between each anatomical site (oropharynx, urethra and anorectum) in men who have sex with men (MSM). We constructed four scenarios: (1) mouthwash had no effect; (2) mouthwash increased the susceptibility of the oropharynx; (3) mouthwash reduced the transmissibility from the oropharynx; (4) the combined effect of mouthwash from scenarios 2 and 3. SETTING: We used data at three anatomical sites from 4873 MSM attending Melbourne Sexual Health Centre in 2018 and 2019 to calibrate our models and data from the USA, Netherlands and Thailand for sensitivity analyses. PARTICIPANTS: Published available data on MSM with multisite infections of gonorrhoea. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidence of gonorrhoea. RESULTS: The overall incidence of gonorrhoea was 44 (95% CI 37 to 50)/100 person-years (PY) in scenario 1. Under scenario 2 (20%-80% mouthwash coverage), the total incidence increased (47-60/100 PY) and at all three anatomical sites by between 7.4% (5.9%-60.8%) and 136.6% (108.1%-177.5%). Under scenario 3, with the same coverage, the total incidence decreased (20-39/100 PY) and at all anatomical sites by between 11.6% (10.2%-13.5%) and 99.8% (99.2%-100%). Under scenario 4, changes in the incidence depended on the efficacy of mouthwash on the susceptibility or transmissibility. The effect on the total incidence varied (22-55/100 PY), and at all anatomical sites, there were increases of nearly 130% and large declines of almost 100%. CONCLUSIONS: The effect of mouthwash on gonorrhoea incidence is largely predictable depending on whether it increases susceptibility to or reduces the transmissibility of gonorrhoea.


Subject(s)
Anti-Infective Agents, Local , Gonorrhea , Sexual and Gender Minorities , Gonorrhea/epidemiology , Gonorrhea/prevention & control , Homosexuality, Male , Humans , Incidence , Male , Models, Theoretical , Mouthwashes , Neisseria gonorrhoeae
9.
Sci China Life Sci ; 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1460457

ABSTRACT

Triage management plays important roles in hospitalized patients for disease severity stratification and medical burden analysis. Although progression risks have been extensively researched for numbers of diseases, other crucial indicators that reflect patients' economic and time costs have not been systematically studied. To address the problems, we developed an automatic deep learning based Auto Triage Management (ATM) Framework capable of accurately modelling patients' disease progression risk and health economic evaluation. Based on them, we can first discover the relationship between disease progression and medical system cost, find potential features that can more precisely aid patient triage in resource allocation, and allow treatment plan searching that has cured patients. Applying ATM in COVID-19, we built a joint model to predict patients' risk, the total length of stay (LoS) and cost when at-admission, and remaining LoS and cost at a given hospitalized time point, with C-index 0.930 and 0.869 for risk prediction, mean absolute error (MAE) of 5.61 and 5.90 days for total LoS prediction in internal and external validation data.

10.
Front Med (Lausanne) ; 8: 764493, 2021.
Article in English | MEDLINE | ID: covidwho-1450820

ABSTRACT

[This corrects the article DOI: 10.3389/fmed.2020.584342.].

11.
Signal Transduct Target Ther ; 6(1): 290, 2021 Aug 02.
Article in English | MEDLINE | ID: covidwho-1344903

ABSTRACT

Emerging evidence suggests that liquid-liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy-but is fast-growing-it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.

12.
World J Stem Cells ; 13(8): 1058-1071, 2021 Aug 26.
Article in English | MEDLINE | ID: covidwho-1441314

ABSTRACT

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people's life health. Two current studies have indicated a favorable role for mesenchymal stem/stromal cells (MSCs) in clinical remission of COVID-19 associated pulmonary diseases, yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction. In the present review, we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury, acute respiratory distress syndrome, and pulmonary fibrosis. Furthermore, we review the underlying mechanism of MSCs including direct- and trans-differentiation, autocrine and paracrine anti-inflammatory effects, homing, and neovascularization, as well as constitutive microenvironment. Finally, we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice. Collectively, this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.

13.
Transportation Research Record ; : 03611981211043813, 2021.
Article in English | Sage | ID: covidwho-1430338

ABSTRACT

The research team has utilized privacy-protected mobile device location data, integrated with COVID-19 case data and census population data, to produce a COVID-19 impact analysis platform that can inform users about the effects of COVID-19 spread and government orders on mobility and social distancing. The platform is being updated daily, to continuously inform decision-makers about the impacts of COVID-19 on their communities, using an interactive analytical tool. The research team has processed anonymized mobile device location data to identify trips and produced a set of variables, including social distancing index, percentage of people staying at home, visits to work and non-work locations, out-of-town trips, and trip distance. The results are aggregated to county and state levels to protect privacy, and scaled to the entire population of each county and state. The research team is making their data and findings, which are updated daily and go back to January 1, 2020, for benchmarking, available to the public to help public officials make informed decisions. This paper presents a summary of the platform and describes the methodology used to process data and produce the platform metrics.

14.
Front Artif Intell ; 4: 672050, 2021.
Article in English | MEDLINE | ID: covidwho-1430749

ABSTRACT

Cohort-independent robust mortality prediction model in patients with COVID-19 infection is not yet established. To build up a reliable, interpretable mortality prediction model with strong foresight, we have performed an international, bi-institutional study from China (Wuhan cohort, collected from January to March) and Germany (Würzburg cohort, collected from March to September). A Random Forest-based machine learning approach was applied to 1,352 patients from the Wuhan cohort, generating a mortality prediction model based on their clinical features. The results showed that five clinical features at admission, including lymphocyte (%), neutrophil count, C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase, could be used for mortality prediction of COVID-19 patients with more than 91% accuracy and 99% AUC. Additionally, the time-series analysis revealed that the predictive model based on these clinical features is very robust over time when patients are in the hospital, indicating the strong association of these five clinical features with the progression of treatment as well. Moreover, for different preexisting diseases, this model also demonstrated high predictive power. Finally, the mortality prediction model has been applied to the independent Würzburg cohort, resulting in high prediction accuracy (with above 90% accuracy and 85% AUC) as well, indicating the robustness of the model in different cohorts. In summary, this study has established the mortality prediction model that allowed early classification of COVID-19 patients, not only at admission but also along the treatment timeline, not only cohort-independent but also highly interpretable. This model represents a valuable tool for triaging and optimizing the resources in COVID-19 patients.

16.
Mil Med Res ; 8(1): 51, 2021 09 13.
Article in English | MEDLINE | ID: covidwho-1416822

ABSTRACT

To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.


Subject(s)
COVID-19/complications , Olfaction Disorders/etiology , Smell , Taste Disorders/etiology , Taste , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Olfaction Disorders/epidemiology , Prevalence , SARS-CoV-2 , Sex Factors , Taste Disorders/epidemiology , Young Adult
17.
International Journal of Environmental Research and Public Health ; 17(8), 2020.
Article in English | CAB Abstracts | ID: covidwho-1409568

ABSTRACT

This paper evaluates the short-term impact of the coronavirus outbreak on 21 leading stock market indices in major affected countries including Japan, Korea, Singapore, the USA, Germany, Italy, and the UK etc. The consequences of infectious disease are considerable and have been directly affecting stock markets worldwide. Using an event study method, our results indicate that the stock markets in major affected countries and areas fell quickly after the virus outbreak. Countries in Asia experienced more negative abnormal returns as compared to other countries. Further panel fixed effect regressions also support the adverse effect of COVID-19 confirmed cases on stock indices abnormal returns through an effective channel by adding up investors' pessimistic sentiment on future returns and fears of uncertainties.

18.
Public Health ; 200: 15-21, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401801

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has resulted in an enormous burden on population health and the economy around the world. Although most cities in the United States have reopened their economies from previous lockdowns, it was not clear how the magnitude of different control measures-such as face mask use and social distancing-may affect the timing of reopening the economy for a local region. This study aimed to investigate the relationship between reopening dates and control measures and identify the conditions under which a city can be reopened safely. STUDY DESIGN: This was a mathematical modeling study. METHODS: We developed a dynamic compartment model to capture the transmission dynamics of COVID-19 in New York City. We estimated model parameters from local COVID-19 data. We conducted three sets of policy simulations to investigate how different reopening dates and magnitudes of control measures would affect the COVID-19 epidemic. RESULTS: The model estimated that maintaining social contact at 80% of the prepandemic level and a 50% face mask usage would prevent a major surge of COVID-19 after reopening. If social distancing were completely relaxed after reopening, face mask usage would need to be maintained at nearly 80% to prevent a major surge. CONCLUSIONS: Adherence to social distancing and increased face mask usage are keys to prevent a major surge after a city reopens its economy. The findings from our study can help policymakers identify the conditions under which a city can be reopened safely.


Subject(s)
COVID-19 , Pandemics , Communicable Disease Control , Humans , Masks , Pandemics/prevention & control , SARS-CoV-2 , United States/epidemiology
19.
Biomed Pharmacother ; 137: 111419, 2021 May.
Article in English | MEDLINE | ID: covidwho-1392160

ABSTRACT

BACKGROUND: Atherosclerosis, inflammatory disease, is a major reason for cardiovascular diseases and stroke. Kaempferol (Kae) has been well-documented to have pharmacological activities in the previous studies. However, the detailed mechanisms by which Kae regulates inflammation, oxidative stress, and apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) remain unknown. METHODS AND RESULTS: The real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure expression levels of circNOL12, nucleolar protein 12 (NOL12), miR-6873-3p, and Fibroblast growth factor receptor substrate 2 (FRS2) in HUVECs treated with either oxidized low-density lipoprotein (ox-LDL) alone or in combination with Kae. The cells viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. The inflammation and oxidative stress were assessed by checking inflammatory factors, Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels in ox-LDL-induced HUVECs. The apoptotic cells were quantified by flow cytometry assay. The western blot assay was used for measuring protein expression. The interaction relationship between miR-6873-3p and circNOL12 or FRS2 was analyzed by dual-luciferase reporter and RNA pull-down assays. Treatment with Kae could inhibit ox-LDL-induced the upregulation of circNOL12 in HUVECs. Importantly, Kae weakened ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs, which was abolished by overexpression of circNOL12. What's more, miR-6873-3p was a target of circNOL12 in HUVECs, and the upregulation of miR-6873-3p overturned circNOL12 overexpression-induced effects on HUVECs treated with ox-LDL and Kae. FRS2 was negatively regulated by miR-6873-3p in HUVECs. CONCLUSION: Kae alleviated ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs by regulating circNOL12/miR-6873-3p/FRS2 axis.


Subject(s)
Adaptor Proteins, Signal Transducing/drug effects , Endothelial Cells/drug effects , Kaempferols/pharmacology , Membrane Proteins/drug effects , MicroRNAs/drug effects , Nuclear Proteins/drug effects , RNA-Binding Proteins/drug effects , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Female , Human Umbilical Vein Endothelial Cells , Humans , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism
20.
Cell Res ; 31(8): 847-860, 2021 08.
Article in English | MEDLINE | ID: covidwho-1387284

ABSTRACT

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.


Subject(s)
Antiviral Agents/metabolism , COVID-19/pathology , Coronavirus Envelope Proteins/metabolism , Respiratory Distress Syndrome/etiology , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Apoptosis , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Coronavirus Envelope Proteins/antagonists & inhibitors , Coronavirus Envelope Proteins/genetics , Cytokines/metabolism , Disease Models, Animal , Half-Life , Humans , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutagenesis, Site-Directed , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Spleen/metabolism , Spleen/pathology , Viral Load , Virulence
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