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1.
Health Science Reports ; 5(3):e560, 2022.
Article in English | Wiley | ID: covidwho-1797887

ABSTRACT

Background and Aims Globally, coronavirus disease-2019 (COVID-19) is persistent in many countries and presents a major threat to public health. Critically, elderly individuals, especially those with underlying disease, poor nutritional and immune functions, are highly susceptible. Therefore, we analyzed the epidemiological features in elderly COVID-19 patients. Methods In total, 126 patients were recruited in the Fifth Affiliated Hospital of Sun Yat-sen University, China from January 2020 to March 2020 (including 103 confirmed COVID-19 patients and 23 elderly suspected cases). Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. We assessed nutritional risks in elderly patients by calculating the Geriatric Nutritional Risk Index (GNRI). Results When compared with young patients, elderly patients were more likely to have underlying comorbidities and received nutritional support and intensive care unit treatment. Elderly patients had significantly lower levels of the following: lymphocyte percentages, red blood cell counts, hemoglobin levels, and serum albumin values. When compared with suspected COVID-19 elderly cases, elderly patients had significantly lower red blood cell counts and hemoglobin levels. The average GNRI of suspected cases and confirmed patients indicated no nutritional risk. There were no marked differences in GNRI values between groups. Conclusion Nutritional risk assessments may provide valuable information for predicting a COVID-19 prognosis, especially in elderly patients. Anemia prevention and management should be actively and timely provided. GNRI is a potentially prognostic factor for hospitalized elderly patients. Moreover, it is also important to follow up discharged patients for continuous nutritional observations.

2.
Virol Sin ; 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1730151

ABSTRACT

The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2 (ACE2). Here, by using lentivirus based pseudotypes bearing spike protein, we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry. Finally, we showed that the current predominant Delta variant, although with high infectivity and high syncytium formation, also entered cells through clathrin-mediated endocytosis. These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325084

ABSTRACT

The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324350

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) is one of the most wide-spread and threatening infectious diseases in human history. Experts in the field of medicine and biology are working to develop methods to treat and prevent COVID-19. Currently, COVID-19 is predominantly treated with symptomatic therapy and there is still a lack of effective antiviral therapy. Therefore, the prevention and control of novel coronavirus is primarily focused on vaccine development. Several vaccines have been developed, but their relative efficacy and safety have not been proven. Therefore, the aim of this study is to investigate the efficacy and safety of COVID-19 vaccines. Methods: and analysis: The electronic databases we will use to retrieve information include PubMed, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database and Weipu Electronics. The retrieval period is from the establishment of the database to March 2021. All randomized controlled trials in humans vaccinated with COVID-19 were collected, and data were independently selected and extracted according to predesigned inclusion/exclusion criteria. Full-text screening, data extraction and quality assessment were conducted independently by two reviewers. Two additional investigators will conduct report quality, risk of bias, sensitivity analysis and subgroup analysis to ensure the reliability of our study results. The software RevMan 5.3 was used for statistical analysis. Systematic review and meta-analyses will be conducted to evaluate the pooled evidence of efficacy and safety of the COVID-19 vaccines. Result: This study will evaluate the efficacy and safety of the COVID-19 vaccines. Conclusion: The conclusions of this study will provide an evidence-based analysis of the safety and efficacy of COVID-19 vaccines. Systematic review registration: PROSPERO CRD42021242581

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323658

ABSTRACT

Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain. Methods: By calculating the sample size of random sampling, anonymous questionnaire was used in Wen Juan Xing survey platform. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations with samples of healthcare workers and nonhealth care workers. Findings: A total of 2580 respondents have completed the questionnaire, including 1,329 healthcare workers and 1,251 nonhealthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the nonhealthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12–2.07);vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44–3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03–3.90). Among the nonhealthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31–2.11);vaccine-resistant individuals were also more likely to be female (AOR =1.87, 95% CI: 1.16–3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40–7.62). There are great differences between healthcare workers and nonhealthcare workers in their cognition and attitude towards vaccines. Interpretation: Our study shows that healthcare workers are more willing to be vaccinated than nonhealthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for nonhealthcare workers.Funding: Medical and Technology Project of Zhejiang ProvinceDeclaration of Interest: None to declare. Ethical Approval: This study is a nation-wide cross-sectional study in China;the ethics committee ofAffiliated Hospital of Hangzhou Normal University approved all the procedures performed.

7.
Nature ; 603(7903): 919-925, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1655591

ABSTRACT

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
8.
Cell ; 185(5): 860-871.e13, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1650841

ABSTRACT

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge, and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members, as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies, sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.


Subject(s)
Immune Evasion/physiology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/immunology , Binding Sites , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Cryoelectron Microscopy , Humans , Mutagenesis, Site-Directed , Neutralization Tests , Protein Binding , Protein Domains/immunology , Protein Structure, Quaternary , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Surface Plasmon Resonance , Virus Attachment
9.
Sci Rep ; 11(1): 24432, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585772

ABSTRACT

Despite the initial success of some drugs and vaccines targeting COVID-19, understanding the mechanism underlying SARS-CoV-2 disease pathogenesis remains crucial for the development of further approaches to treatment. Some patients with severe Covid-19 experience a cytokine storm and display evidence of inflammasome activation leading to increased levels of IL-1ß and IL-18; however, other reports have suggested reduced inflammatory responses to Sars-Cov-2. In this study we have examined the effects of the Sars-Cov-2 envelope (E) protein, a virulence factor in coronaviruses, on inflammasome activation and pulmonary inflammation. In cultured macrophages the E protein suppressed inflammasome priming and NLRP3 inflammasome activation. Similarly, in mice transfected with E protein and treated with poly(I:C) to simulate the effects of viral RNA, the E protein, in an NLRP3-dependent fashion, reduced expression of pro-IL-1ß, levels of IL-1ß and IL-18 in broncho-alveolar lavage fluid, and macrophage infiltration in the lung. To simulate the effects of more advanced infection, macrophages were treated with both LPS and poly(I:C). In this setting the E protein increased NLRP3 inflammasome activation in both murine and human macrophages. Thus, the Sars-Cov-2 E protein may initially suppress the host NLRP3 inflammasome response to viral RNA while potentially increasing NLRP3 inflammasome responses in the later stages of infection. Targeting the Sars-Cov-2 E protein especially in the early stages of infection may represent a novel approach to Covid-19 therapy.


Subject(s)
Coronavirus Envelope Proteins/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SARS-CoV-2/metabolism , Animals , Bronchoalveolar Lavage Fluid/chemistry , COVID-19/pathology , COVID-19/virology , Coronavirus Envelope Proteins/genetics , Down-Regulation/drug effects , Endoplasmic Reticulum Stress , Humans , Inflammasomes/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Janus Kinases/genetics , Janus Kinases/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein/deficiency , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Poly I-C/pharmacology , RNA, Viral/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
10.
Lancet Infect Dis ; 22(1): 73-84, 2022 01.
Article in English | MEDLINE | ID: covidwho-1452446

ABSTRACT

BACKGROUND: Improved seasonal influenza vaccines for older adults that can induce broadly cross-reactive antibodies and enhanced T-cell responses, particularly against A H3N2 viruses, while avoiding egg-adaptive antigenic changes, are needed. We aimed to show that the Matrix-M-adjuvanted quadrivalent nanoparticle influenza vaccine (qNIV) was immunologically non-inferior to a licensed, standard-dose quadrivalent inactivated influenza vaccine (IIV4) in older adults. METHODS: This was a phase 3 randomised, observer-blinded, active-comparator controlled trial done across 19 US community-based clinical research sites during the 2019-20 influenza season. Participants were clinically stable and community-dwelling, aged at least 65 years, and were randomised in a 1:1 ratio using an interactive web response system to receive a single intramuscular dose of qNIV or IIV4. The primary objective was to describe safety and show that qNIV was immunologically non-inferior to IIV4. The primary outcomes were adverse events by treatment group and comparative haemagglutination-inhibiting antibody responses (assayed with egg-propagated virus) on day 28, summarised in terms of the ratio of geometric mean titres (GMTRqNIV/IIV4) and seroconversion rate (SCR) difference between participants receiving qNIV or IIV4 for all four vaccine homologous influenza strains. The immunogenicity outcome was measured in the per-protocol population. Non-inferiority was shown if the lower bound of the two-sided 95% CI on the GMTRqNIV/IIV4 was at least 0·67 and the lower bound of the two-sided 95% CI on the SCR difference -was at least -10%. The study is registered with clinicaltrials.gov, NCT04120194, and is active and not recruiting. FINDINGS: 2742 adults were assessed for eligibility and 2654 were enrolled and randomised between Oct 14, 2019, and Oct 25, 2019; 1333 participants were randomised to the qNIV group and 1319 to the IIV4 group (two participants withdrew consent before being assigned to a group). qNIV showed immunological non-inferiority to IIV4: GMTRqNIV/IIV4 for the four vaccine homologous influenza strains was A/Brisbane 1·09 (95% CI 1·03 to 1·15), A/Kansas 1·19 (1·11 to 1·27), B/Maryland 1·03 (0·99 to 1·07), and B/Phuket 1·23 (1·16 to 1·29); and SCR difference was A/Brisbane 5·0 (95% CI 1·9 to 8·1), A/Kansas 7·3 (3·6 to 11·1), B/Maryland 0·5 (-1·9 to 2·9), and B/Phuket 8·5 (5·0 to 11·9). 659 (49·4%) of 1333 of participants in the qNIV group and 551 (41·8%) of 1319 participants in the IIV4 group had at least one treatment-emergent adverse event. More solicited adverse events were reported by participants in the qNIV group (551 [41·3%] of 1333) than in the IIV4 group (420 [31·8%] of 1319), and were comprised primarily of mild to moderate transient injection site pain (341 [25·6%] in the qNIV group vs 212 [16·1%] in the IIV4 group). INTERPRETATION: qNIV was well tolerated and produced qualitatively and quantitatively enhanced humoral and cellular immune response in older adults compared with IIV4. qNIV might enhance the effectiveness of seasonal influenza vaccination, and future studies to show clinical efficacy are planned. FUNDING: Novavax.


Subject(s)
/administration & dosage , Antibodies, Viral/blood , Immunogenicity, Vaccine , Influenza Vaccines/immunology , Influenza Vaccines/standards , Influenza, Human/prevention & control , Nanoparticles/administration & dosage , Saponins/administration & dosage , Aged , Female , Hemagglutination Inhibition Tests , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/immunology , Male , Nanoparticles/chemistry , Saponins/chemistry , Seasons
11.
View (Beijing) ; : 20200082, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1411072

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis and global panic. This infectious disease is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Digital polymerase chain reaction (dPCR), which is an emerging nucleic acid amplification technology that allows absolute quantification of nucleic acids, plays an important role in the detection of SARS-CoV-2. In this review, we introduce the principle and advantages of dPCR, and review the applications of dPCR in the COVID-19 pandemic, including detection of low copy number viruses, measurement of the viral load, preparation of reference materials, monitoring of virus concentration in the environment, detection of viral mutations, and evaluation of anti-SARS-CoV-2 drugs. We also discuss the challenges of dPCR in clinical practice.

14.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-1387275

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
15.
Front Public Health ; 9: 709056, 2021.
Article in English | MEDLINE | ID: covidwho-1365588

ABSTRACT

Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain. Methods: An anonymous questionnaire was used in Wen Juan Xing survey platform. All the respondents were divided into healthcare workers and non-healthcare workers. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations among the samples of healthcare workers and non-healthcare workers. Results: A total of 2,580 respondents completed the questionnaire, including 1,329 healthcare workers and 1,251 non-healthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the non-healthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12-2.07); vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44-3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03-3.90). Among the non-healthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31-2.11); vaccine-resistant individuals were also more likely to be female (AOR = 1.87, 95% CI: 1.16-3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40-7.62). There are great differences between healthcare workers and non-healthcare workers in their cognition and attitude toward vaccines. Conclusions: Our study shows that healthcare workers are more willing to be vaccinated than non-healthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for non-healthcare workers.


Subject(s)
COVID-19 Vaccines , COVID-19 , China/epidemiology , Cross-Sectional Studies , Female , Health Personnel , Humans , Male , Pandemics , SARS-CoV-2 , Surveys and Questionnaires , Vaccination
16.
Natl Sci Rev ; 8(8): nwab053, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1358471

ABSTRACT

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

17.
Cities ; 118:103361, 2021.
Article in English | ScienceDirect | ID: covidwho-1322027

ABSTRACT

The mental health of healthcare workers during epidemics is a complex topic. The outbreak of coronavirus disease 2019 (COVID-19) that occurred in late 2019 has become a global public health threat and provides an opportunity to investigate this topic. Based on a large-scale investigation of Chinese healthcare workers during the COVID-19 epidemic, the article tests the assumption that the socioeconomic level of a city affects the mental health status of healthcare workers. The result is interesting and important: the mental health status of this population differs based on the city level. Hospital level, hospital type and departments risk level were investigated separately. With regard to the degree of anxiety, depression and post-traumatic stress disorder (PTSD), there were obvious differences based on the city level: the negative mental health impacts increase with increasing city level, such that healthcare workers in first-tier cities have the least negative mental health impacts, while those in third-tier cities have the most. City level reflects the degree of urban development, resource richness, resident satisfaction, and positive social atmosphere. Urban prosperity may affect mental health.

18.
Front Immunol ; 12: 697074, 2021.
Article in English | MEDLINE | ID: covidwho-1311376

ABSTRACT

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


Subject(s)
Adenovirus Vaccines/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Schedule , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccination/methods , Adenovirus Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Pan troglodytes , RNA, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Transfection , Treatment Outcome
19.
Chem Soc Rev ; 50(17): 9741-9765, 2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1309470

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has accelerated efforts to develop high-performance antiviral surface coatings while highlighting the need to build a strong mechanistic understanding of the chemical design principles that underpin antiviral surface coatings. Herein, we critically summarize the latest efforts to develop antiviral surface coatings that exhibit virus-inactivating functions through disrupting lipid envelopes or protein capsids. Particular attention is focused on how cutting-edge advances in material science are being applied to engineer antiviral surface coatings with tailored molecular-level properties to inhibit membrane-enveloped and non-enveloped viruses. Key topics covered include surfaces functionalized with organic and inorganic compounds and nanoparticles to inhibit viruses, and self-cleaning surfaces that incorporate photocatalysts and triplet photosensitizers. Application examples to stop COVID-19 are also introduced and demonstrate how the integration of chemical design principles and advanced material fabrication strategies are leading to next-generation surface coatings that can help thwart viral pandemics and other infectious disease threats.


Subject(s)
Antiviral Agents/chemistry , Coated Materials, Biocompatible , Drug Design , COVID-19 , Humans , Pandemics , SARS-CoV-2
20.
Int J Health Plann Manage ; 36(5): 1561-1574, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1220217

ABSTRACT

BACKGROUND: Reliable and detailed nationwide data on the prevalence and distribution of mental disorders among healthcare workers in China during the coronavirus disease 2019 (COVID-19) outbreak are scarce. METHODS: We did a cross-sectional online survey from March 2 to 2 April 2020 and a total of 19,379 healthcare workers from 25 provinces participated. Depression, anxiety and post-traumatic stress disorder (PTSD) were assessed by the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and PTSD Checklist for DSM-5 (PCL-5), respectively. RESULTS: The age-standardized prevalence of depression, anxiety and PTSD was 15.5%, 12.7% and 5.2%, respectively. Frontline workers had higher prevalence estimates than non-frontline workers (depression: 18.2% vs. 13.9%; anxiety: 14.7% vs. 11.6%; PTSD: 6.1% vs. 4.6%). Subgroups who were nurses, were married or had dependent children reported higher prevalence of depression, anxiety and PTSD. Despite of the large variations, the prevalence of mental disorders was lowest in East China, followed by Middle China, and highest in West China. CONCLUSION: Healthcare workers faced enormous stress not only from the direct risk presented by the COVID-19 outbreak, but also from the profound changes in their professional practice. Prevalence of adverse psychological outcomes has a significant association with geographically distribution of health resources and regional economic level. Sufficient medical resource may be a protective factor to mental health condition of healthcare personnel when such a public health emergency happened.


Subject(s)
COVID-19 , Mental Disorders , Stress Disorders, Post-Traumatic , Anxiety , China/epidemiology , Cross-Sectional Studies , Health Personnel , Humans , Mental Disorders/epidemiology , Prevalence , SARS-CoV-2 , Stress Disorders, Post-Traumatic/epidemiology
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