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2.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572660

ABSTRACT

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.


Subject(s)
Antibody-Dependent Enhancement/immunology , Leukocytes/virology , SARS-CoV-2/pathogenicity , COVID-19/immunology , Cells, Cultured , Gene Expression Profiling , Humans , Immune Sera/immunology , Leukocytes/metabolism , Receptors, IgG/metabolism , Virus Replication/immunology
3.
Preprint in English | EuropePMC | ID: ppcovidwho-295329

ABSTRACT

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, Interpretability and usability. Built upon our previous work, in this study, we proposed an open natural language processing development framework and evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The generated corpora derived out of the texts from multiple intuitions and gold standard annotation are tested on a single institution's rule set has the performances in F1 score of 0.876, 0.706 and 0.694, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study.

4.
mBio ; 12(5): e0234221, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1494971

ABSTRACT

The recent emergence and spread of zoonotic viruses highlights that animal-sourced viruses are the biggest threat to global public health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an HKU2-related bat coronavirus that was spilled over from Rhinolophus bats to swine, causing large-scale outbreaks of severe diarrhea disease in piglets in China. Unlike other porcine coronaviruses, SADS-CoV possesses broad species tissue tropism, including primary human cells, implying a significant risk of cross-species spillover. To explore host dependency factors for SADS-CoV as therapeutic targets, we employed genome-wide CRISPR knockout library screening in HeLa cells. Consistent with two independent screens, we identified the zinc finger DHHC-type palmitoyltransferase 17 (ZDHHC17 or ZD17) as an important host factor for SADS-CoV infection. Through truncation mutagenesis, we demonstrated that the DHHC domain of ZD17 that is involved in palmitoylation is important for SADS-CoV infection. Mechanistic studies revealed that ZD17 is required for SADS-CoV genomic RNA replication. Treatment of infected cells with the palmitoylation inhibitor 2-bromopalmitate (2-BP) significantly suppressed SADS-CoV infection. Our findings provide insight on SADS-CoV-host interactions and a potential therapeutic application. IMPORTANCE The recent emergence of deadly zoonotic viral diseases, including Ebola virus and SARS-CoV-2, emphasizes the importance of pandemic preparedness for the animal-sourced viruses with potential risk of animal-to-human spillover. Over the last 2 decades, three significant coronaviruses of bat origin, SARS-CoV, MERS-CoV, and SARS-CoV-2, have caused millions of deaths with significant economy and public health impacts. Lack of effective therapeutics against these coronaviruses was one of the contributing factors to such losses. Although SADS-CoV, another coronavirus of bat origin, was only known to cause fatal diarrhea disease in piglets, the ability to infect cells derived from multiple species, including human, highlights the potential risk of animal-to-human spillover. As part of our effort in pandemic preparedness, we explore SADS-CoV host dependency factors as targets for host-directed therapeutic development and found zinc finger DHHC-type palmitoyltransferase 17 is a promising drug target against SADS-CoV replication. We also demonstrated that a palmitoylation inhibitor, 2-bromopalmitate (2-BP), can be used as an inhibitor for SADS-CoV treatment.


Subject(s)
Acyltransferases/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Alphacoronavirus/pathogenicity , Nerve Tissue Proteins/metabolism , Acyltransferases/genetics , Adaptor Proteins, Signal Transducing/genetics , Alphacoronavirus/drug effects , Animals , COVID-19/metabolism , HeLa Cells , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nerve Tissue Proteins/genetics , Palmitates/pharmacology , SARS Virus/drug effects , SARS Virus/pathogenicity , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Swine
7.
Virol Sin ; 36(5): 879-889, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1174014

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Mice , Mice, Transgenic , Primates , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Inactivated/immunology
8.
Front Psychol ; 12: 649180, 2021.
Article in English | MEDLINE | ID: covidwho-1156160

ABSTRACT

This study uses the Planned Risk Information Seeking Model (PRISM) to estimate the public's information seeking and avoidance intentions during the COVID-19 outbreak based on an online sample of 1031 Chinese adults and provides support for the applicability of PRISM framework in the situation of a novel high-level risk. The results indicate that information seeking is primarily directed by informational subjective norms (ISN) and perceived seeking control (PSC), while the main predictors of information avoidance include ISN and attitude toward seeking. Because ISN are the strongest predictor of both information seeking and avoidance, the way the public copes with COVID-19 information may be strongly affected by individuals' social environment. Furthermore, a significant relationship between risk perception and affective risk response is identified. Our results also indicate that people who perceive greater knowledge of COVID-19 are more likely to report greater knowledge insufficiency, which results in less information avoidance.

9.
J Am Med Inform Assoc ; 28(6): 1275-1283, 2021 06 12.
Article in English | MEDLINE | ID: covidwho-1120596

ABSTRACT

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 SignSym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.


Subject(s)
COVID-19/diagnosis , Electronic Health Records , Information Storage and Retrieval/methods , Natural Language Processing , Deep Learning , Humans , Symptom Assessment/methods
10.
BMC Infect Dis ; 21(1): 155, 2021 Feb 08.
Article in English | MEDLINE | ID: covidwho-1069544

ABSTRACT

BACKGROUND: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. METHODS: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. RESULTS: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P <  0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046). CONCLUSIONS: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.


Subject(s)
COVID-19/physiopathology , Adult , Aged , COVID-19/diagnosis , Child, Preschool , China , Comorbidity , Cough , Disease Outbreaks , Female , Fever , Hospitalization , Humans , Infant , Lung/diagnostic imaging , Lymphopenia , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed
11.
Nano Today ; 37: 101092, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1065492

ABSTRACT

The current widespread of COVID-19 all over the world, which is caused by SARS-CoV-2 virus, has again emphasized the importance of development of point-of-care (POC) diagnostics for timely prevention and control of the pandemic. Compared with labor- and time-consuming traditional diagnostic methods, POC diagnostics exhibit several advantages such as faster diagnostic speed, better sensitivity and specificity, lower cost, higher efficiency and ability of on-site detection. To achieve POC diagnostics, developing POC detection methods and correlated POC devices is the key and should be given top priority. The fast development of microfluidics, micro electro-mechanical systems (MEMS) technology, nanotechnology and materials science, have benefited the production of a series of portable, miniaturized, low cost and highly integrated POC devices for POC diagnostics of various infectious diseases. In this review, various POC detection methods for the diagnosis of infectious diseases, including electrochemical biosensors, fluorescence biosensors, surface-enhanced Raman scattering (SERS)-based biosensors, colorimetric biosensors, chemiluminiscence biosensors, surface plasmon resonance (SPR)-based biosensors, and magnetic biosensors, were first summarized. Then, recent progresses in the development of POC devices including lab-on-a-chip (LOC) devices, lab-on-a-disc (LOAD) devices, microfluidic paper-based analytical devices (µPADs), lateral flow devices, miniaturized PCR devices, and isothermal nucleic acid amplification (INAA) devices, were systematically discussed. Finally, the challenges and future perspectives for the design and development of POC detection methods and correlated devices were presented. The ultimate goal of this review is to provide new insights and directions for the future development of POC diagnostics for the management of infectious diseases and contribute to the prevention and control of infectious pandemics like COVID-19.

12.
J Med Virol ; 92(9): 1549-1555, 2020 09.
Article in English | MEDLINE | ID: covidwho-995989

ABSTRACT

The outbreak of 2019 novel coronavirus (COVID-19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID-19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID-19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID-19 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C-reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 ± 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID-19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID-19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Coinfection , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Biomarkers , COVID-19/complications , COVID-19/virology , China/epidemiology , Comorbidity , Disease Management , Humans , Influenza, Human/complications , Influenza, Human/virology , Patient Outcome Assessment , Pneumonia, Viral/etiology , Public Health Surveillance , Symptom Assessment , Tomography, X-Ray Computed
14.
Preprint in English | bioRxiv | ID: ppbiorxiv-382416

ABSTRACT

Hyperinflammation and lymphopenia provoked by SARS-CoV-2-activated macrophages contribute to the high mortality of Coronavirus Disease 2019 (COVID-19) patients. Thus, defining host pathways aberrantly activated in patient macrophages is critical for developing effective therapeutics. We discovered that G9a, a histone methyltransferase that is overexpressed in COVID-19 patients with high viral load, activates translation of specific genes that induce hyperinflammation and impairment of T cell function or lymphopenia. This noncanonical, pro-translation activity of G9a contrasts with its canonical epigenetic function. In endotoxin-tolerant (ET) macrophages that mimic conditions which render patients with pre-existing chronic inflammatory diseases vulnerable to severe symptoms, our chemoproteomic approach with a biotinylated inhibitor of G9a identified multiple G9a-associated translation regulatory pathways that were upregulated by SARS-CoV-2 infection. Further, quantitative translatome analysis of ET macrophages treated progressively with the G9a inhibitor profiled G9a-translated proteins that unite the networks associated with viral replication and the SARS-CoV-2-induced host response in severe patients. Accordingly, inhibition of G9a-associated pathways produced multifaceted, systematic effects, namely, restoration of T cell function, mitigation of hyperinflammation, and suppression of viral replication. Importantly, as a host-directed mechanism, this G9a-targeted, combined therapeutics is refractory to emerging antiviral-resistant mutants of SARS-CoV-2, or any virus, that hijacks host responses.

15.
Revista Argentina de Clínica Psicológica ; 29(5):285, 2020.
Article in English | ProQuest Central | ID: covidwho-908440

ABSTRACT

In the context of COVID-19 Epidemic, the education industry across the country has been forced to adopt online teaching. This paper analyzes the changes of education pattern with the perspective of teacher-teaching mode, student-learning mode and mode of school management, and it explains the existence of teaching platform, teaching methods, teacher-student interaction, network status and other issues of large-scale online teaching. This paper suggests carrying out the design goal of teaching problem oriented teaching mode in seven aspects from teaching content design, student academic analysis, courses for ideological and political education design, teaching method design, teaching process design, and teaching quality monitoring. During the process, four levels of talent training requirements are satisfied including courses for ideological and political education goals, classroom teaching goals, curriculum teaching goals and professional training goals. The goal problem oriented mode is implemented in the course of Fire and Explosion for the major of Safety Engineering, which provides a beneficial reference for the reform of teaching mode and the improvement of online teaching quality.

16.
JAMA Intern Med ; 180(10): 1356-1362, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-718296

ABSTRACT

Importance: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. Objective: To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19. Design, Setting, and Participants: In this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China. Exposures: SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase-polymerase chain reaction testing of nasopharyngeal samples. Main Outcomes and Measures: The primary outcome was SARS-CoV-2-specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level. Results: Of the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2-specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, <40), and 2 patients who showed very high titers of NAbs, with ID50 levels of 15 989 and 21 567. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. NAbs were unable to cross-react with SARS-associated CoV and NAb titers correlated with the spike-binding antibodies targeting S1 (r = 0.451; 95% CI, 0.320-0.564; P < .001), receptor binding domain (r = 0.484; 95% CI, 0.358-0.592; P < .001), and S2 regions (r = 0.346; 95% CI, 0.204-0.473; P < .001). NAb titers at the time of discharge were significantly higher in the 82 men (1417 [IQR, 541-2253]) than those in the 93 women (905 [IQR, 371-1687]) (median difference, 512; 95% CI, 82-688; P = .01) and at the time of follow-up in 56 male patients (1049 [IQR, 552-2454]) vs 61 female patients (751 [IQR, 216-1301]) (median difference, 298; 95% CI, 86-732; P = .009). Plasma NAb titers were significantly higher in 56 older (1537 [IQR, 877-2427) and 63 middle-aged (1291 [IQR, 504-2126]) patients than in 56 younger patients (459 [IQR, 225-998]) (older vs younger: median difference, 1078; 95% CI, 548-1287; P < .001; middle-aged vs younger: median difference, 832; 95% CI, 284-1013; P < .001). The NAb titers were correlated with plasma C-reactive protein levels (r = 0.508; 95% CI, 0.386-0.614; P < .001) and negatively correlated with lymphocyte counts (r = -0.427; 95% CI, -0.544 to -0.293; P < .001) at the time of admission. Conclusions and Relevance: In this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.


Subject(s)
Antibodies, Neutralizing/analysis , Betacoronavirus , Coronavirus Infections/blood , Coronavirus Infections/therapy , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Adult , COVID-19 , China , Cohort Studies , Coronavirus Infections/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
17.
Am J Infect Control ; 49(3): 361-365, 2021 03.
Article in English | MEDLINE | ID: covidwho-712424

ABSTRACT

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 and causing a global public health emergency. During the outbreak, Wuhan was the first reported and hardest-hit city. With the dramatic drop in number of confirmed cases and subsequent ending of Wuhan lock down, asymptomatic carriers and patients in their recovery period still pose an increased risk. Strict and effective infection control protocols should be established and followed.


Subject(s)
COVID-19/prevention & control , Disease Outbreaks , Endoscopy, Gastrointestinal , Infection Control/methods , Surgery Department, Hospital/organization & administration , COVID-19/epidemiology , China/epidemiology , Humans , SARS-CoV-2
18.
Cell ; 182(3): 722-733.e11, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-628738

ABSTRACT

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS Virus/immunology , Universal Design , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/chemistry , COVID-19 , COVID-19 Vaccines , Cell Line, Tumor , Chlorocebus aethiops , Coronavirus Infections/virology , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus/chemistry , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs/immunology , Receptors, Virus/metabolism , SARS Virus/chemistry , SARS-CoV-2 , Sf9 Cells , Specific Pathogen-Free Organisms , Spodoptera , Transfection , Vaccination/methods , Vero Cells , Viral Vaccines
19.
Cell ; 182(1): 50-58.e8, 2020 07 09.
Article in English | MEDLINE | ID: covidwho-343611

ABSTRACT

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/pathology , Disease Models, Animal , Mice, Transgenic , Pneumonia, Viral/pathology , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Female , Humans , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic/genetics , Pandemics , Peptidyl-Dipeptidase A/genetics , SARS-CoV-2 , Viral Tropism , Weight Loss
20.
Eur Child Adolesc Psychiatry ; 29(6): 749-758, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-155414

ABSTRACT

Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12-18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students' awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19.


Subject(s)
Anxiety/epidemiology , Coronavirus Infections/psychology , Depression/epidemiology , Disease Outbreaks , Pneumonia, Viral/psychology , Students/psychology , Adolescent , Anxiety/psychology , Betacoronavirus , COVID-19 , Child , China/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Depression/psychology , Female , Humans , Male , Mental Health , Pandemics , Pneumonia, Viral/epidemiology , Prevalence , Risk Factors , SARS-CoV-2 , Students/statistics & numerical data , Surveys and Questionnaires
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