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2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327593

ABSTRACT

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to the poor stability, most current mRNA delivery platforms need to be stored at -20 °C or -70 °C. Here we present lyophilized thermostable mRNA loaded lipid nanoparticles, which could be stored at room temperature with long-term stability. We demonstrate the applicability of lyophilization techniques to different mRNA sequences and lipid components. Three lyophilized vaccines targeting wild-type, Delta and Omicron SARS-CoV-2 variant were prepared and demonstrated to be able induce high-level of IgG titer and neutralization response. In the Delta challenge in vivo experiment, the lyophilized mRNA vaccine successfully protected the mice from infection and clear the virus. This lyophilization platform could significantly improve the accessibility of mRNA vaccine or therapeutics, particularly in remote regions.

3.
Gut ; 71(2): 238-253, 2022 02.
Article in English | MEDLINE | ID: covidwho-1622066

ABSTRACT

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.


Subject(s)
Family Health , Helicobacter Infections/prevention & control , Helicobacter pylori , Infection Control/organization & administration , Adolescent , Adult , Aged , Child , Child, Preschool , China , Consensus , Delphi Technique , Helicobacter Infections/diagnosis , Helicobacter Infections/transmission , Humans , Infant , Middle Aged , Young Adult
4.
Innovation (N Y) ; 3(1): 100181, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1595417

ABSTRACT

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

5.
Heliyon ; 7(8): e07829, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1531295

ABSTRACT

AIMS: To explore the structural characteristics and influential factors of psychological stress of urban residents in Jiangxi province during the COVID-19 pandemic through a survey of psychological stress, personality traits, family function and life satisfaction. METHODS: By the convenient sampling, 1422 urban residents from Jiangxi province were assessed with Eysenck Personality Questionnaire Short Scale (EPQ-RSC), Psychological Questionnaires for Emergent Events of Public Health (PQEEPH), Family APGAR Scale (APGAR) and Satisfaction With Life Scale (SWLS). The relation among personality traits, psychological stress, family function and life satisfaction during the COVID-19 pandemic was analyzed by using the canonical correlation analysis and the serial mediation model. RESULTS: (1) Among the estimated correlation coefficients, the first two pairs were significant (P < 0.001 in each). (2) In the first pair of canonical variables, the loadings of neuroticism and neurasthenia were the higher (0.94, 0.70). (3) Neuroticism and life satisfaction mediated the relationship between family function and neurasthenia (ß neuroticism = -0.174; 95%CI:-0.224, -0.134; ß life satisfaction = -0.034, 95%CI:-0.012, -0.062), respectively. In addition, serial mediation analyses indicated that the association of family function and neurasthenia is mediated by neuroticism and life satisfaction in a sequential manner (ß = -0.010; 95%CI:-0.020, -0.004). CONCLUSIONS: During the COVID-19 pandemic, neuroticism was closely related to psychological stress of urban residents, especially neurasthenia. In addition, the serial mediating effect of neuroticism and life satisfaction played an important role in the process of family function influencing neurasthenia. These findings contributed to a more comprehensive understanding of the influential factors for psychological stress of urban residents during the COVID-19 pandemic.

6.
Cell Prolif ; 54(9): e13091, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1320384

ABSTRACT

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.


Subject(s)
Cytokines/analysis , Placenta/virology , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Viral Proteins/isolation & purification , Adult , Amniotic Fluid/chemistry , COVID-19/pathology , Female , Fetal Blood/chemistry , Humans , Infant, Newborn , Macrophages/immunology , Nucleic Acid Amplification Techniques , Placenta/immunology , Pregnancy , RNA, Viral/blood , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Viral Proteins/blood
7.
Mol Cell ; 81(10): 2135-2147.e5, 2021 05 20.
Article in English | MEDLINE | ID: covidwho-1117323

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global pandemic. CoVs are known to generate negative subgenomes (subgenomic RNAs [sgRNAs]) through transcription-regulating sequence (TRS)-dependent template switching, but the global dynamic landscapes of coronaviral subgenomes and regulatory rules remain unclear. Here, using next-generation sequencing (NGS) short-read and Nanopore long-read poly(A) RNA sequencing in two cell types at multiple time points after infection with SARS-CoV-2, we identified hundreds of template switches and constructed the dynamic landscapes of SARS-CoV-2 subgenomes. Interestingly, template switching could occur in a bidirectional manner, with diverse SARS-CoV-2 subgenomes generated from successive template-switching events. The majority of template switches result from RNA-RNA interactions, including seed and compensatory modes, with terminal pairing status as a key determinant. Two TRS-independent template switch modes are also responsible for subgenome biogenesis. Our findings reveal the subgenome landscape of SARS-CoV-2 and its regulatory features, providing a molecular basis for understanding subgenome biogenesis and developing novel anti-viral strategies.


Subject(s)
COVID-19 , Genome, Viral , High-Throughput Nucleotide Sequencing , RNA, Viral , SARS-CoV-2 , Animals , COVID-19/genetics , COVID-19/metabolism , Caco-2 Cells , Chlorocebus aethiops , Humans , RNA, Viral/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Vero Cells
8.
Nat Ecol Evol ; 5(5): 600-608, 2021 05.
Article in English | MEDLINE | ID: covidwho-1111986

ABSTRACT

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.


Subject(s)
COVID-19 , Chiroptera , Angiotensin-Converting Enzyme 2 , Animals , Humans , Peptidyl-Dipeptidase A/genetics , Receptors, Virus/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
9.
Cell Res ; 31(4): 395-403, 2021 04.
Article in English | MEDLINE | ID: covidwho-1091494

ABSTRACT

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.


Subject(s)
COVID-19/pathology , Coinfection/pathology , Influenza A virus/physiology , Orthomyxoviridae Infections/pathology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/deficiency , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Cell Line , Coinfection/virology , Humans , Influenza A virus/isolation & purification , Lung/pathology , Mice , Mice, Transgenic , Orthomyxoviridae Infections/virology , RNA, Guide/metabolism , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Severity of Illness Index , Viral Load , Virus Internalization
10.
Nano Today ; 36: 101019, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-907175

ABSTRACT

In just a few months, SARS-CoV-2 and the disease it causes, COVID-19, created a worldwide pandemic. Virologists, biologists, pharmacists, materials scientists, and clinicians are collaborating to develop efficient treatment strategies. Overall, in addition to the use of clinical equipment to assist patient rehabilitation, antiviral drugs and vaccines are the areas of greatest focus. Given the physical size of SARS-CoV-2 and the vaccine delivery platforms currently in clinical trials, the relevance of nanotechnology is clear, and previous antiviral research using nanomaterials also supports this connection. Herein we briefly summarize current representative strategies regarding nanomaterials in antiviral research. We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment.

11.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-587

ABSTRACT

Circulating in China and 75 other countries and territories, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public h

12.
Emerg Microbes Infect ; 9(1): 1175-1179, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-361278

ABSTRACT

Different primers/probes sets have been developed all over the world for the nucleic acid detection of SARS-CoV-2 by quantitative real time polymerase chain reaction (qRT-PCR) as a standard method. In our recent study, we explored the feasibility of droplet digital PCR (ddPCR) for clinical SARS-CoV-2 nucleic acid detection compared with qRT-PCR using the same primer/probe sets issued by Chinese Center for Disease Control and Prevention (CDC) targeting viral ORF1ab or N gene, which showed that ddPCR could largely minimize the false negatives reports resulted by qRT-PCR [Suo T, Liu X, Feng J, et al. ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens. medRxiv [Internet]. 2020;2020.02.29.20029439. Available from: https://medrxiv.org/content/early/2020/03/06/2020.02.29.20029439.abstract]. Here, we further stringently compared the performance of qRT-PCR and ddPCR for 8 primer/probe sets with the same clinical samples and conditions. Results showed that none of 8 primer/probe sets used in qRT-PCR could significantly distinguish true negatives and positives with low viral load (10-4 dilution). Moreover, false positive reports of qRT-PCR with UCDC-N1, N2 and CCDC-N primers/probes sets were observed. In contrast, ddPCR showed significantly better performance in general for low viral load samples compared to qRT-PCR. Remarkably, the background readouts of ddPCR are relatively lower, which could efficiently reduce the production of false positive reports.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Multiplex Polymerase Chain Reaction , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , COVID-19 , DNA Primers , DNA Probes , Humans , Multiplex Polymerase Chain Reaction/methods , Pandemics , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/standards , SARS-CoV-2 , Sensitivity and Specificity , Viral Load
13.
Emerg Microbes Infect ; 9(1): 1259-1268, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-342833

ABSTRACT

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , COVID-19 , False Negative Reactions , Humans , Limit of Detection , Pandemics , RNA, Viral/genetics , SARS-CoV-2 , Viral Load/methods
14.
Nature ; 582(7813): 557-560, 2020 06.
Article in English | MEDLINE | ID: covidwho-137432

ABSTRACT

The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood1-3. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.


Subject(s)
Aerosols/analysis , Aerosols/chemistry , Bathroom Equipment , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Hospitals , Pneumonia, Viral/virology , Workplace , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Crowding , Disinfection , Humans , Intensive Care Units , Masks , Medical Staff , Pandemics/prevention & control , Patients/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , RNA, Viral/analysis , SARS-CoV-2 , Social Isolation , Ventilation
15.
Emerg Microbes Infect ; 9(1): 761-770, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-29222

ABSTRACT

Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.


Subject(s)
Bronchoalveolar Lavage Fluid , Chemokines/analysis , Coronavirus Infections/genetics , Cytokines/analysis , Leukocytes, Mononuclear , Pneumonia, Viral/genetics , Transcriptome , Apoptosis , Betacoronavirus , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Humans , Lymphopenia , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , RNA-Seq , SARS-CoV-2 , Signal Transduction , Tumor Suppressor Protein p53
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