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1.
Journal of Development Economics ; 145:145, 2020.
Article in English | GIM | ID: covidwho-1720289

ABSTRACT

This study uses satellite data to detect agricultural straw burning and estimates its impact on air pollution and health in China. We find that straw burning increases particulate matter pollution and causes people to die from cardiorespiratory diseases. We estimate that a 10 g/m3 increase in PM2.5 increases mortality by 3.25%. Middle-aged and old people in rural areas are particularly sensitive to straw burning pollution. Exploratory analysis of China's programs to subsidize straw recycling suggests that extending these programs to all the straw burning regions would bring about a health benefit that is an order of magnitude larger than the cost.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315584

ABSTRACT

In this paper, we investigate the distributed link removal strategy for networked meta-population epidemics. In particular, a deterministic networked susceptible-infected-recovered (SIR) model is considered to describe the epidemic evolving process. In order to curb the spread of epidemics, we present the spectrum-based optimization problem involving the Perron-Frobenius eigenvalue of the matrix constructed by the network topology and transition rates. A modified distributed link removal strategy is developed such that it can be applied to the SIR model with heterogeneous transition rates on weighted digraphs. The proposed approach is implemented to control the COVID-19 pandemic by using the reported infected and recovered data in each state of Germany. The numerical experiment shows that the infected percentage can be significantly reduced by using the distributed link removal strategy.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312727

ABSTRACT

The rapid expansion of COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantages of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates has entered clinical trials with a two-dose immunization regimen. However, the waning antibodies response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concern about a short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form which encoded SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular response, and conferred a near-complete protection against wild SARS-CoV-2 infection in lungs of hACE2 transgenic mice. Noticeably, high levels of neutralizing antibodies response induced by mRNA-RBD vaccination could maintain for at least 6.5 months and conferred a long-term remarkable protection for hACE2 transgenic mice against SARS-CoV-2 infection in sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310722

ABSTRACT

Background: In December 2019, Wuhan witnessed the outbreak of an “unexplained pneumonia” caused by a novel coronavirus strain infection and was dubbed the COVID-19 by the WHO. The disease quickly spread to China. This study aimed to investigate the disease’s evolving epidemiological history, as well as analyze the clinical and CT imaging characteristics, treatment regimens, and patients’ prognosis. Methods: : This was a retrospective study whose cases were 64 patients with a confirmed diagnosis of COVID-19. The clinical data were obtained from patients who were admitted to the isolation ward from 21 January 2020 to 19 February 2020. Results: : 60 out of 64 patients had a definitive history of exposure to people who had traveled from Wuhan City. The median time from onset of symptoms to first hospital admission was 3.9±1.9 days. The initial symptoms included fever (46/64), dry cough (38/64), fatigue or myalgia (23/64), sore throat (10/64), diarrhea (3/64) along with late-onset symptoms like chest pains (2/64) and headaches (2/64). The majority of the patients (43/64) had normal white blood cell counts while 29.7 % (19/64) had leukopenia. Only two patients (3.1 %) presented with leukocytosis. 58 of the 64patients had abnormal radiological findings on chest CTs. The first chest CTs (within 2 days) was more sensitive in detecting COVID-19 infection (85.9 %) compared to the initial RT-PCR (56.3 %;p<0.01). The CTs showed lesions in multiple lung lobes in three-quarters of the patients while 15.6 % had lesions localized to one lobe. Most of the lesions were typically dense with ground-glass opacity co-existing with consolidation or cord-like shadows. Most of these patients (50/64) have recovered and got discharged giving a mean length of hospital stay of 13.5±4.8 days. Our hospital unit has not reported any COVID-19 related death so far. Conclusions: : Early intervention in COVID-19 disease improves patients’ prognosis. Our data demonstrate the superiority of early radiological tests ahead of RT-PCR. The initial and dynamic CT changes in COVID-19 patients along with other clinical data shared above can better guide clinical decision making.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307596

ABSTRACT

Background: There is no consensus as to when and how to reopen schools during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate the safety of reopening universities and colleges using a combined strategy in China. Methods: This cross-sectional study included 13,116 staffs and postgraduate students who have returned to the four campuses of the University of Science and Technology of China from 17 February (students returned from 12 May) to 2 July 2020. The returning to school was guided by a combined strategy including use of personal protective equipment, management of transportation, serological and nucleic acid tests for COVID-19, quarantine, and restrictions in and out of campus. Epidemiology history and COVID-19 related symptoms (fever, cough, and dyspnoea) were recorded in a subset of participants using an online questionnaire. Results: Among 13,116 participants, 4067 tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid and no positive results were identified. Of 9049 participants who chose to conduct antibody tests, 28 (0.3%) tested positive but no one was confirmed by the additional viral nucleic acid tests. Online questionnaires were collected from 5741 participants (mean 25.1 years, 35% female). High-risk exposures and COVID-19 related symptoms were reported in 8.3% and 7.4% of participants, respectively. Comorbidities (hypertension, diabetes, chronic pulmonary disease, and chronic kidney disease) were rare (0.2%-1.5%). Conclusions: Using a combined strategy for COVID-19 prevention and control, safely reopening of universities and colleges in low-risk regions is possible and laboratory screening for SARS-CoV-2 infection may not be necessary. Further studies need to cautiously evaluate the safety of reopening schools, if any, in the middle- and high-risk regions.

6.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1621335

ABSTRACT

After binding to its cell surface receptor angiotensin converting enzyme 2 (ACE2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell through directly fusing with plasma membrane (cell surface pathway) or undergoing endocytosis traveling to lysosome/late endosome for membrane fusion (endocytic pathway). However, the endocytic entry regulation by host cell remains elusive. Recent studies show ACE2 possesses a type I PDZ binding motif (PBM) through which it could interact with a PDZ domain-containing protein such as sorting nexin 27 (SNX27). In this study, we determined the ACE2-PBM/SNX27-PDZ complex structure, and, through a series of functional analyses, we found SNX27 plays an important role in regulating the homeostasis of ACE2 receptor. More importantly, we demonstrated SNX27, together with retromer complex (the core component of the endosomal protein sorting machinery), prevents ACE2/virus complex from entering lysosome/late endosome, resulting in decreased viral entry in cells where the endocytic pathway dominates. The ACE2/virus retrieval mediated by SNX27-retromer could be considered as a countermeasure against invasion of ACE2 receptor-using SARS coronaviruses.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Endosomes/metabolism , SARS-CoV-2 , Sorting Nexins/chemistry , COVID-19/virology , Cell Line , Cell Line, Tumor , Cell Membrane/metabolism , Crystallography, X-Ray , Cytosol/metabolism , Endocytosis , Gene Expression Profiling , HEK293 Cells , HeLa Cells , Homeostasis , Humans , Lentivirus , Lysosomes/metabolism , Peptides/chemistry , Protein Binding , Protein Conformation , Protein Domains , Sorting Nexins/metabolism , Virus Internalization
7.
PLoS One ; 16(9): e0257878, 2021.
Article in English | MEDLINE | ID: covidwho-1443847

ABSTRACT

Extracellular microRNAs (miRNAs) have been proposed to function in cross-kingdom gene regulation. Among these, plant-derived miRNAs of dietary origin have been reported to survive the harsh conditions of the human digestive system, enter the circulatory system, and regulate gene expression and metabolic function. However, definitive evidence supporting the presence of plant-derived miRNAs of dietary origin in mammals has been difficult to obtain due to limited sample sizes. We have developed a bioinformatics pipeline (ePmiRNA_finder) that provides strident miRNA classification and applied it to analyze 421 small RNA sequencing data sets from 10 types of human body fluids and tissues and comparative samples from carnivores and herbivores. A total of 35 miRNAs were identified that map to plants typically found in the human diet and these miRNAs were found in at least one human blood sample and their abundance was significantly different when compared to samples from human microbiome or cow. The plant-derived miRNA profiles were body fluid/tissue-specific and highly abundant in the brain and the breast milk samples, indicating selective absorption and/or the ability to be transported across tissue/organ barriers. Our data provide conclusive evidence for the presence of plant-derived miRNAs as a consequence of dietary intake and their cross-kingdom regulatory function within human circulating system.


Subject(s)
Computational Biology/methods , MicroRNAs/genetics , Plants/genetics , Sequence Analysis, RNA/methods , Animal Feed/analysis , Animals , Brain Chemistry , Carnivora/genetics , Diet , Female , Herbivory/genetics , Humans , Milk, Human/chemistry , Organ Specificity , RNA, Plant/genetics , Sample Size
9.
Nat Commun ; 12(1): 4195, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301166

ABSTRACT

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Animals , Binding Sites , Cell Line , Cricetinae , Crystallography, X-Ray , Dogs , HeLa Cells , Humans , Mutation , Protein Binding , Protein Domains , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
10.
Nat Commun ; 12(1): 776, 2021 02 03.
Article in English | MEDLINE | ID: covidwho-1062751

ABSTRACT

The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantage of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates have entered clinical trials with a two-dose immunization regimen. However, the waning antibody response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concerns about a possible short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form that encoded the SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a near-complete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. Noticeably, the high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19 Vaccines/genetics , Cell Line , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Pandemics/prevention & control , RNA, Messenger/genetics , RNA, Messenger/immunology , RNA, Viral/genetics , RNA, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Viral Envelope Proteins/immunology
11.
Nature ; 584(7819): 120-124, 2020 08.
Article in English | MEDLINE | ID: covidwho-381744

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/chemistry , Antibodies, Viral/pharmacology , Betacoronavirus/chemistry , Binding, Competitive , COVID-19 , Cell Line , Chlorocebus aethiops , Crystallization , Crystallography, X-Ray , Female , Humans , In Vitro Techniques , Macaca mulatta/immunology , Macaca mulatta/virology , Male , Models, Molecular , Neutralization Tests , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Binding/drug effects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Viral Load/immunology
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