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1.
J Epidemiol Glob Health ; 2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2060197

ABSTRACT

BACKGROUND: Glutamine family amino acids such as glutamate, pyroglutamate, and glutamine have been shown to play important roles in COVID-19. However, it is still unclear about the role of pyroglutamate in COVID-19. Thus, we use a two-sample Mendelian randomization (MR) study to identify the genetic causal link between blood pyroglutamine levels and COVID-19 risk. METHODS: Pyroglutamine genetic instrumental variables (IVs) were chosen from the largest pyroglutamine-associated genome-wide association studies (GWAS). The largest COVID-19 GWAS dataset was employed to evaluate the causal link between blood pyroglutamine levels and COVID-19 risk using two-sample MR analysis. RESULTS: We found no significant pleiotropy or heterogeneity of pyroglutamine-associated genetic IVs in COVID-19 GWAS. Interestingly, we found that as pyroglutamine genetically increased, the risk of COVID-19 decreased using inverse variance weighted (IVW) (Beta = - 0.644, p = 0.003; OR = 0.525, 95% CI [0.346-0.798]) and weighted median (Beta = - 0.609, p = 0.013; OR = 0.544, 95% CI [0.337-0.878]). CONCLUSION: Our analysis suggests a causal link between genetically increased pyroglutamine and reduced risk of COVID-19. Thus, pyroglutamine may be a protective factor for patients with COVID-19.

2.
J Med Virol ; 94(7): 3233-3239, 2022 07.
Article in English | MEDLINE | ID: covidwho-1756618

ABSTRACT

Although individuals with coronavirus disease 2019 (COVID-19) are known to be at increased risk for other conditions resulting from pathogenic changes (including metaplastic or anaplastic) in the lungs and other organs and organ systems, it is still unknown whether COVID-19 affects childhood intelligence. The present two-sample Mendelian randomization study aims to identify the genetic causal link between COVID-19 and childhood intelligence. Four COVID-19 genetic instrumental variants (IVs) were chosen from the largest genome-wide association studies (GWAS) for COVID-19 (hospitalized vs. population) (6406 cases and 902 088 controls of European ancestry). The largest childhood intelligence GWAS (n = 12 441 individuals of European ancestry) was used to evaluate the effect of the identified COVID-19-associated genetic IVs on childhood intelligence. We found that as the genetic susceptibility to COVID-19 increased, childhood intelligence followed a decreasing trend, according to mr_egger (ß = -0.156; p = 0.601; odds ratio [OR] = 0.856; 95% confidence interval [CI]: 0.522-1.405), simple mode (ß = -0.126; p = 0.240; OR = 0.882; 95% CI: 0.745-1.044), and weighted mode (ß = -0.121; p = 0.226; OR = 0.886; 95% CI: 0.758-1.036) analyses. This trend was further demonstrated by the weighted median (ß = -0.134; p = 0.031; OR = 0.875; 95% CI: 0.774-0.988) and the inverse variance weighted (ß = -0.152; p = 0.004; OR = 0.859; 95% CI: 0.776-0.952). Our analysis suggests a causal link between genetically increased COVID-19 and decreased childhood intelligence. Thus, COVID-19 may be a risk factor for declines in childhood intelligence.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Intelligence , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323719

ABSTRACT

The SARS-CoV-2 has led to a worldwide health crisis. The ACE2 has been identified as the entry receptor in a species-specific manner. Classic laboratory mice were insusceptible since the virus cannot use murine ACE2 orthologue. Animal models rely on gene modification on the virus or the host. However, these mice were restricted in limited genetic backgrounds and did not support natural infection. Here we showed two wild-type inbred lines (CAST and FEW) from Genetic Diversity mice supported authentic SARS-CoV-2 infection, and developed mild to moderate interstitial pneumonia, along with infiltrating inflammatory cells. Particularly, FEW featured age-dependent damages, while CAST charactered by pulmonary fibrosis. Genome and transcriptome comparative analysis suggested the mutated ACE2 was not responsible for SARS-CoV-2 infection in CAST and FEW, and the differential gene expressions in immune response and immune cell may be risk factors for the infection. In summary, the GD mice, derived from the multi-parental panel, provided promising murine models for exploring sophisticated pathogenesis in SARS-CoV-2.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311706

ABSTRACT

The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.Funding: This work was supported by the National Natural Science Foundation of China (31570891;31872736), the National Key Research and Development Program of China (2016YFA0500302;2020YFA0707800), the National Key Research and Development Program (2020YFA0707500) and the Strategic Priority Research Program (XDB29010000). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (81921005). We thank National Mega projects of China for Major Infectious Diseases (2017ZX10304402), CAMS initiative for Innovative Medicine of China (2016-12M-2-006) and The National Natural Science Foundation of China (82041008) for the support on the animal model study. Conflict of Interest: The authors have no conflicts of interest to declare.Ethical Approval: All experiments with live SARS-CoV-2 viruses were carried out in the enhanced biosafety level 3 (P3+) facilities in the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) approved by the National Health Commission of the People’s Republic of China. All animals care and use were in accordance with the Guide for the Care and Use of Laboratory Animals of the Chinese Association for Laboratory Animal Science. All procedures of animal handling were approved by the Animal Care Committee of Peking University Health Science Center.

7.
Cell Mol Immunol ; 19(2): 210-221, 2022 02.
Article in English | MEDLINE | ID: covidwho-1608557

ABSTRACT

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.


Subject(s)
Angiotensin-Converting Enzyme 2/administration & dosage , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cell-Derived Microparticles/metabolism , Cholesterol/metabolism , Endosomes/chemistry , Macrophages, Alveolar/metabolism , SARS-CoV-2/metabolism , A549 Cells , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Female , Humans , Hydrogen-Ion Concentration , Lysosomes/chemistry , Mice , Mice, Inbred ICR , Mice, Transgenic , Oxidation-Reduction , RAW 264.7 Cells , Treatment Outcome , Vero Cells
8.
Int J Environ Res Public Health ; 18(24)2021 12 10.
Article in English | MEDLINE | ID: covidwho-1572453

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic has resulted in significant delays and cost overrun in construction projects. The implementation of health and safety (H&S) technologies is one of the most important strategies to alleviate the adverse impacts of COVID-19 on the construction industry and help the industry adapt to the new normal. This study aims to evaluate the adoption of H&S technologies for pandemic management in the construction sector under the COVID-19 pandemic. Semi-structured interviews with eighteen practitioners engaged from construction companies and technology firms were conducted to collect their views on the driving forces and issues of the adoption of H&S technologies for pandemic management in Chinese construction projects. The results reveal that the major H&S technologies used included the health quick response (QR) code system, artificial intelligence (AI)-powered fever monitoring, and site access control system. These technologies were reported to be effective in preventing the spread of the pandemic in workplaces. The findings of the study amplify that the pandemic may serve as an acceleration of the adoption of H&S technologies in the construction sector. Other technologies, such as building information modeling, drones, AI-based safety monitoring, and robotics, however, were seldom used in the studied projects. The interviewees addressed several problems regarding the implementation of these technologies. High costs of technologies, a lack of client support, and disruptions to the normal work process were the main hurdles of the adoption of these technologies. The results indicated that the external influence factor-the COVID-19 pandemic-could considerably drive the use of H&S technologies, whereas the internal influence factors-cost and compatibility of technology-might be the major barriers to technology adoption. To encourage the wider use of H&S technologies in construction, the government is recommended to support the technology transformation by granting financial subsidies for costs involved in innovation adoption. Project owners may consider investing substantially in H&S technologies that can strengthen their resilient and innovative ability to adapt to the post-COVID-19 landscape. The present results will be useful to industry stakeholders and researchers interested in developing H&S technologies for combating the COVID-19 pandemic and future crises.


Subject(s)
COVID-19 , Pandemics , Artificial Intelligence , China/epidemiology , Humans , Pandemics/prevention & control , SARS-CoV-2 , Technology
9.
Mol Biomed ; 2(1): 29, 2021.
Article in English | MEDLINE | ID: covidwho-1515465

ABSTRACT

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection. Supplementary Information: The online version contains supplementary material available at 10.1186/s43556-021-00054-z.

10.
Cell Host Microbe ; 29(2): 222-235.e4, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-987276

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.


Subject(s)
Alarmins/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Neutrophils/drug effects , SARS-CoV-2/drug effects , Animals , COVID-19/metabolism , COVID-19/virology , Disease Models, Animal , Female , Humans , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/metabolism , Transcriptome , Viral Load
11.
J Virol Methods ; 279: 113855, 2020 05.
Article in English | MEDLINE | ID: covidwho-827847

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) causes very high mortality in newborn piglets. The mucosal immune system in the gut must eliminate potential pathogens while maintaining a mutually beneficial relationship with the commensal microbiota. Antibodies derived from the secretory immunoglobulin A (SIgA) class, act as the first line of antigen-specific immunity in the gut by recognizing both pathogens and commensals. Therefore, the measurement of SIgA levels is an important index in evaluating PEDV infections and immune status. A simple and rapid method for the detection of PEDV-specific SIgA using an immunochromatographic test strip has been developed; incorporating a colloidal gold-labeled anti-SIgA secretory component (SC) mAb probe for the detection of anti-PEDV-specific SIgA in swine. On the strip, a gold-labeled anti-SIgA SC mAb was applied to a conjugate pad; purified PEDV particles and goat anti-mouse antibodies were blotted onto a nitrocellulose membrane to form the test and control lines, respectively. Results showed that the immunochromatographic test strip had high sensitivity and specificity. When compared with enzyme-linked immunosorbent assay, kappa value suggesting that the strip could be used to detect PEDV specific SIgA in colostrum samples. Furthermore, the strip assay is rapid and easy to perform with no requirement for professional-level skills or equipment. We found that the immunochromatographic test strip was a rapid, sensitive, and reliable method for the identification of PEDV specific SIgA, indicating its suitability for epidemiological surveillance as well as vaccine immunity when studying PEDV.


Subject(s)
Antibodies, Viral/analysis , Colostrum/immunology , Immunoassay/methods , Immunoglobulin A, Secretory/isolation & purification , Porcine epidemic diarrhea virus/immunology , Animals , Female , Gold Colloid , Reagent Strips , Sensitivity and Specificity , Specific Pathogen-Free Organisms , Swine , Swine Diseases/diagnosis , Swine Diseases/immunology , Swine Diseases/virology
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