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1.
BioMed Research International ; : 1-8, 2022.
Article in English | Academic Search Complete | ID: covidwho-1789057

ABSTRACT

Purpose. To report the first complete fox coronavirus (CoV) genome sequence obtained through genome-wide amplifications and to understand the adaptive evolution of fox CoV. Methods. Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results. Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species-specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion. The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments. [ FROM AUTHOR] Copyright of BioMed Research International is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
Sci Rep ; 12(1): 5539, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1768852

ABSTRACT

Changes in the aerosol composition of sulfate (SO42-) and nitrate (NO3-) from 2012 to 2019 have been captured as a paradigm shift in the region downwind of China. Specifically, SO42- dramatically decreased and NO3- dramatically increased over downwind locations such as western Japan due to the faster reduction of SO2 emissions than NOx emissions and the almost constant trend of NH3 emissions from China. Emissions from China sharply decreased during COVID-19 lockdowns in February-March 2020, after which China's economic situation seemed to recover going into 2021. Given this substantial change in Chinese emissions, it is necessary to clarify the impact of long-range PM2.5 transport into the leeward of East Asia. In this study, ground-based aerosol compositions observed at three sites in western Japan were analysed. The concentrations of PM2.5, SO42- and NO3- decreased in 2020 (during COVID-19) compared with 2018-2019 (before COVID-19). In 2021 (after COVID-19), PM2.5 and NO3- increased and SO42- was unchanged. This suggests the returning long-range PM2.5 transport in 2021. From numerical simulations, the status of Chinese emissions during COVID-19 did not explain this returning impact in 2021. This study shows that the status of Chinese emissions in 2021 recovered to that before COVID-19.


Subject(s)
Air Pollutants , COVID-19 , Air Pollutants/analysis , COVID-19/epidemiology , China/epidemiology , Communicable Disease Control , Environmental Monitoring , Far East/epidemiology , Humans , Pandemics , Particulate Matter/analysis
3.
Energy Build ; 263: 112055, 2022 May 15.
Article in English | MEDLINE | ID: covidwho-1763714

ABSTRACT

Restricting social distancing is an effective means of controlling the COVID-19 pandemic, resulting in a sharp drop in the utilization of commercial buildings. However, the specific changes in the operating parameters are not clear. This study aims to quantify the impact of COVID-19 lockdowns on commercial building energy consumption and the indoor environment, including correlation analysis. A large green commercial building in Dalian, China's only country to experience five lockdowns, has been chosen. We compared the performance during the lockdown to the same period last year. The study found that the first lockdown caused a maximum 63.5% drop in monthly energy consumption, and the second lockdown was 55.2%. The energy consumption per unit area in 2020 dropped by 55.4% compared with 2019. In addition, during the lockdown, the compliance rate of indoor thermal environment increased by 34.7%, and indoor air quality was 9.5%. These findings could partly explain the short-term and far-reaching effects of the lockdown on the operating parameters of large commercial buildings. Humans are likely to coexist with COVID-19 for a long time, and commercial buildings have to adapt to new energy and health demands. Effective management strategies need to be developed.

4.
BMC Health Serv Res ; 22(1): 284, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1724482

ABSTRACT

BACKGROUND: The present study aimed 1) to examine the effects of epidemic-related job stressors, perceived social support and organizational support on the burnout and well-being of Chinese healthcare workers in the period of COVID-19 regular epidemic prevention and control and 2) to investigate the moderating effects of social support and organizational support on the relationship between job stressors and burnout and well-being within the theoretical framework of the Job Demands-Resources (JD-R) model. METHODS: A sample of healthcare workers (N = 3477) from 22 hospitals in Beijing, China participated in the cross-sectional investigation in October 2020 and reported epidemic-related job stressors, perceived social support, organizational support, burnout, anxiety and depression symptoms. RESULTS: 1) Medical doctors, females, people aged from 30 to 50, and those who worked in the second line during the pandemic reported higher scores of psychological symptoms and burnout in the period of regular epidemic prevention and control; 2) Epidemic-related job stressors positively predicted burnout, anxiety, and depression among healthcare workers; 3) Perceived social support and organizational support were negatively related to reported burnout, anxiety and depression symptoms; 4) Social support reduced the adverse effects of epidemic-related job stressors on anxiety and depression but enhanced the association between stressors and burnout; 5) Organizational support mitigated the adverse effects of epidemic-related job stressors on depression. CONCLUSION: The results shed light on preventing burnout and enhancing the psychological well-being of healthcare workers under epidemic prevention and control measures by reducing epidemic-related job stressors and strengthening personal and organizational support systems.


Subject(s)
Burnout, Professional , COVID-19 , Aged , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Burnout, Psychological , COVID-19/epidemiology , Cross-Sectional Studies , Female , Health Personnel/psychology , Humans , Job Satisfaction , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328670

ABSTRACT

Changes in the aerosol composition of sulfate (SO 4 2− ) and nitrate (NO 3 − ) from 2012 to 2019 have been captured as a paradigm shift in the region downwind of China. Specifically, SO 4 2− dramatically decreased and NO 3 − dramatically increased over downwind locations such as western Japan due to the faster reduction of SO 2 emissions than NO x emissions and the almost constant trend of NH 3 emissions from China. Emissions from China sharply decreased during COVID-19 lockdowns in February–March 2020, after which China’s economic situation seemed to recover going into 2021. Given this substantial change in Chinese emissions, it is necessary to clarify the impact of long-range PM 2.5 transport over East Asia. In this study, ground-based aerosol compositions observed at three sites in western Japan were analysed. The concentrations of PM 2.5 , SO 4 2− and NO 3 − decreased in 2020 (during COVID-19) compared with 2018–2019 (before COVID-19). In 2021 (after COVID-19), PM 2.5 and NO 3 − increased and SO 4 2− was unchanged. This suggests the returning impact of long-range PM 2.5 transport in 2021. From numerical simulations, the status of Chinese emissions during COVID-19 did not explain this returning impact in 2021. This study shows that the status of Chinese emissions in 2021 was close to that before COVID-19.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323783

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. Our study aimed to utilize bioinformatics method to analyze the expression profiling by high throughput sequencing in human bronchial organoids/primary human airway epithelial infected with SARS-CoV-2 to identify the potentially crucial genes and pathways associated with COVID-19. Methods: : We analyzed microarray datasets GSE153970 and GSE150819 derived from the GEO database. Firstly, the Differentially expressed genes (DEGs) in human bronchial organoids/primary human airway epithelial infected with SARS-CoV-2. Next, the DEGs were used for GO and KEGG pathway enrichment analysis. Then, the PPI network was constructed and Cytoscape was used to find the key genes. Results: : Gene expression profiles of GSE153970 and GSE150819, in all 12 samples were analyzed. A total of 145 DEGs and 5 hub genes were identified in SARS-CoV-2. Meanwhile, we found that the 145 genes are associated with immune responses and the top 5 hub genes including CXCL8, CXCL1, CXCL2, CCL20, and CSF2 were mainly related to leukocyte migration, endoplasmic reticulum lumen, receptor ligand activity. In addition, the results also showed that the hub genes were associated with Cytokine−cytokine receptor interaction, IL−17 signaling pathway, and Rheumatoid arthritis in SARS-CoV-2 infection. Conclusion: The five crucial genes consisting of CXCL8 , CXCL1 , CXCL2 , CCL20 , and CSF2 were considered as hub genes of SARS-CoV-2, which may be used as diagnostic biomarkers or molecular targets for the treatment of SARS-CoV-2. It is evidenced that bioinformatics analyses in SARS-CoV-2 can be useful for understanding the underlying molecular mechanism and exploring effective therapeutic targets.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315658

ABSTRACT

Since early 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly across the world. As at the date of writing this article, the disease has been globally reported in 223 countries and regions, infected over 108 million people and caused over 2.4 million deaths (https://covid19.who.int/, accessed on Feb. 17, 2021). Avoiding person-to-person transmission is an effective approach to control and prevent the pandemic. However, many daily activities, such as transporting goods in our daily life, inevitably involve person-to-person contact. Using an autonomous logistic vehicle to achieve contact-less goods transportation could alleviate this issue. For example, it can reduce the risk of virus transmission between the driver and customers. Moreover, many countries have imposed tough lockdown measures to reduce the virus transmission (e.g., retail, catering) during the pandemic, which causes inconveniences for human daily life. Autonomous vehicle can deliver the goods bought by humans, so that humans can get the goods without going out. These demands motivate us to develop an autonomous vehicle, named as Hercules, for contact-less goods transportation during the COVID-19 pandemic. The vehicle is evaluated through real-world delivering tasks under various traffic conditions.

8.
Environ Sci Pollut Res Int ; 2022 Feb 06.
Article in English | MEDLINE | ID: covidwho-1669935

ABSTRACT

The spread of highly pathogenic avian influenza H5N1 has posed a major threat to global public health. Understanding the spatiotemporal outbreak characteristics and environmental factors of H5N1 outbreaks is of great significance for the establishment of effective prevention and control systems. The time and location of H5N1 outbreaks in poultry and wild birds officially confirmed by the World Organization for Animal Health from 2005 to 2019 were collected. Spatial autocorrelation analysis and multidistance spatial agglomeration analysis methods were used to analyze the global outbreak sites of H5N1. Combined with remote sensing data, the correlation between H5N1 outbreaks and environmental factors was analyzed using binary logistic regression methods. We analyzed the correlation between the H5N1 outbreak and environmental factors and finally made a risk prediction for the global H5N1 outbreaks. The results show that the peak of the H5N1 outbreaks occurs in winter and spring. H5N1 outbreaks exhibit aggregation, and a weak aggregation phenomenon is noted on the scale close to 5000 km. Water distance, road distance, railway distance, wind speed, leaf area index (LAI), and specific humidity were protective factors for the outbreak of H5N1, and the odds ratio (OR) were 0.985, 0.989, 0.995, 0.717, 0.832, and 0.935, respectively. Temperature was a risk factor with an OR of 1.073. The significance of these ORs was greater than 95%. The global risk prediction map was obtained. Given that the novel coronavirus (COVID-19) is spreading globally, the methods and results of this study can provide a reference for studying the spread of COVID-19.

10.
Biomedicines ; 10(1)2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1638079

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting about 25% of world population, while there are still no approved targeted therapies. Although platensimycin (PTM) was first discovered to be a broad-spectrum antibiotic, it was also effective against type II diabetes in animal models due to its ability to inhibit both bacterial and mammalian fatty acid synthases (FASN). Herein, we report the pharmacological effect and potential mode of action of PTM against NAFLD in a Western diet/CCI4-induced mouse model and a free fatty acids (FFAs)-induced HepG2 cell model. The proper dose of PTM and its liposome-based nano-formulations not only significantly attenuated the Western diet-induced weight gain and the levels of plasma total triglycerides and glucose, but reduced liver steatosis in mice according to histological analyses. Western blotting analysis showed a reduced protein level of FASN in the mouse liver, suggesting that PTM intervened in the development of NAFLD through FASN inhibition. PTM reduced both the protein and mRNA levels of FASN in FFAs-induced HepG2 cells, as well as the expression of several key proteins in lipogenesis, including sterol regulatory element binding protein-1, acetyl-CoA carboxylase, and stearoyl-CoA desaturase. The expression of lipid oxidation-related genes, including peroxisome proliferator activated receptor α and acyl-CoA oxidase 1, was significantly elevated. In conclusion, our study supports the reposition of PTM to intervene in NAFLD progression, since it could effectively inhibit de novo lipogenesis.

11.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
12.
J Chem Inf Model ; 61(12): 5763-5773, 2021 12 27.
Article in English | MEDLINE | ID: covidwho-1608918

ABSTRACT

COVID-19 caused by a novel coronavirus (SARS-CoV-2) has been spreading all over the world since the end of 2019, and no specific drug has been developed yet. 3C-like protease (3CLpro) acts as an important part of the replication of novel coronavirus and is a promising target for the development of anticoronavirus drugs. In this paper, eight machine learning models were constructed using naïve Bayesian (NB) and recursive partitioning (RP) algorithms for 3CLpro on the basis of optimized two-dimensional (2D) molecular descriptors (MDs) combined with ECFP_4, ECFP_6, and MACCS molecular fingerprints. The optimal models were selected according to the results of 5-fold cross verification, test set verification, and external test set verification. A total of 5766 natural compounds from the internal natural product database were predicted, among which 369 chemical components were predicted to be active compounds by the optimal models and the EstPGood values were more than 0.6, as predicted by the NB (MD + ECFP_6) model. Through ADMET analysis, 31 compounds were selected for further biological activity determination by the fluorescence resonance energy transfer (FRET) method and cytopathic effect (CPE) detection. The results indicated that (+)-shikonin, shikonin, scutellarein, and 5,3',4'-trihydroxyflavone showed certain activity in inhibiting SARS-CoV-2 3CLpro with the half-maximal inhibitory concentration (IC50) values ranging from 4.38 to 87.76 µM. In the CPE assay, 5,3',4'-trihydroxyflavone showed a certain antiviral effect with an IC50 value of 8.22 µM. The binding mechanism of 5,3',4'-trihydroxyflavone with SARS-CoV-2 3CLpro was further revealed through CDOCKER analysis. In this study, 3CLpro prediction models were constructed based on machine learning algorithms for the prediction of active compounds, and the activity of potential inhibitors was determined by the FRET method and CPE assay, which provide important information for further discovery and development of antinovel coronavirus drugs.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Bayes Theorem , Fluorescence Resonance Energy Transfer , Humans , Protease Inhibitors/pharmacology
13.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1556321

ABSTRACT

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Subject(s)
Antiviral Agents/administration & dosage , Azides/administration & dosage , COVID-19/drug therapy , Deoxycytidine/analogs & derivatives , SARS-CoV-2/metabolism , Thymus Gland , Adult , Aged , Aged, 80 and over , Animals , Coronavirus OC43, Human/metabolism , Deoxycytidine/administration & dosage , Female , Humans , Male , Middle Aged , Rats , Thymus Gland/metabolism , Thymus Gland/virology
14.
Front Psychiatry ; 12: 759449, 2021.
Article in English | MEDLINE | ID: covidwho-1551547

ABSTRACT

Introduction: To date, the mental health consequences of children hospitalized with COVID-19 remain unclear. We aimed to assess mental health status in children in the context of COVID-19, with a focus on discharged children. Methods: We recruited discharged children who recovered from COVID-19 and healthy controls between July and September 2020 in Wuhan Children's Hospital. Post-traumatic stress disorder (PTSD), anxiety, depression, and sleep problems were assessed in these children using questionnaires. Univariable and multivariable logistic and linear regressions were conducted to identify risk factors. Results: Totally, there were 152 children (61 discharged children and 91 healthy controls) aged 7-18 years old in our study. An increasing trend in the prevalence of PTSD, anxiety, and depression was observed in the discharged children compared with healthy controls (PTSD: 8.20 vs. 2.20%, anxiety: 22.95 vs. 13.19%; depression: 47.54 vs. 32.97%). Discharged children tended to report more depressive symptoms (ß = 0.39) and less sleep problems (ß = -0.37). Discharged children who lived in nuclear families and had longer hospital stays were more likely to report depression [odds ratio (OR) = 3.68 and 1.14, respectively]. Anxiety symptoms and the severity of sleep problems of discharged children were positively associated with caregivers' depression and PTSD symptoms (OR = 21.88 and 31.09, respectively). Conclusion: In conclusion, PTSD, anxiety, and depression symptoms were common among recovered children 4 months after COVID-19 hospitalization. Children from nuclear family and those had longer hospital stays need special attention. In addition, parental mental health had a significant impact on their children's mental resilience and recovery.

15.
Biomaterials ; 280: 121249, 2022 01.
Article in English | MEDLINE | ID: covidwho-1507702

ABSTRACT

The emergence and spread of antibiotic resistance is one of the biggest challenges in public health. There is an urgent need to discover novel agents against the occurrence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The drug-resistant pathogens are able to grow and persist in infected sites, including biofilms, phagosomes, or phagolysosomes, which are more difficult to eradicate than planktonic ones and also foster the development of drug resistance. For years, various nano-antibacterial agents have been developed in the forms of antibiotic nanocarriers. Inorganic nanoparticles with intrinsic antibacterial activity and inert nanoparticles assisted by external stimuli, including heat, photon, magnetism, or sound, have also been discovered. Many of these strategies are designed to target the unique microenvironment of bacterial infections, which have shown potent antibacterial effects in vitro and in vivo. This review summarizes ongoing efforts on antibacterial nanotherapeutic strategies related to bacterial infection microenvironments, including targeted antibacterial therapy and responsive antibiotic delivery systems. Several grand challenges and future directions for the development and translation of effective nano-antibacterial agents are also discussed. The development of innovative nano-antibacterial agents could provide powerful weapons against drug-resistant bacteria in systemic or local bacterial infections in the foreseeable future.


Subject(s)
Bacterial Infections , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Biofilms , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests
16.
Transl Psychiatry ; 11(1): 499, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447296

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.


Subject(s)
COVID-19 , Animals , Headache , Humans , Pandemics , SARS-CoV-2 , Seizures
17.
Signal Transduct Target Ther ; 6(1): 347, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1437669

ABSTRACT

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Basigin/antagonists & inhibitors , Basigin/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , COVID-19/genetics , Chlorocebus aethiops , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
19.
Building and Environment ; : 108288, 2021.
Article in English | ScienceDirect | ID: covidwho-1372902

ABSTRACT

Leadership in Energy and Environmental Design (LEED) certified buildings aim to offer a sustainable and healthy building environment. Previous studies have shown mixed and inconsistent results on whether occupants in LEED-certified buildings are more satisfied than in non-LEED-certified counterparts. Those studies are usually based on surveys or questionnaires for commercial buildings and were limited by sample size and pre-defined question structures. Since most people would spend more time at home after experiencing the COVID-19 pandemic due to the flexibility to work remotely, assessing the satisfaction with residential buildings benefits future environmental design and certification system development. In this work, we propose a natural language processing-based approach for such assessment. The study collected 16,761 online reviews of 232 LEED-certified and 129 non-LEED-certified apartment buildings from social media, then applied topic modeling and sentiment analysis to evaluate occupants’ satisfaction. Based on topic modeling, we categorized online comments into three topics, 1) location and transportation, 2) running cost, and 3) health and wellbeing. The subsequent sentiment analysis has shown a statistically significant but small or negligible enhancement in the satisfaction occurring in LEED-certified apartments compared to non-LEED-certified ones concerning all three topics. The “significant but small or negligible uptick” has also been found in online star rating and indoor environmental satisfaction. The only exception with a large effect size is lighting which is found to be significantly more satisfying in LEED-certified apartments. Nevertheless, the statistical significance in online star rating disappears when normalized by rent price and property house value.

20.
Signal Transduct Target Ther ; 6(1): 194, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232064

ABSTRACT

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , COVID-19/metabolism , Lung/metabolism , SARS-CoV-2/metabolism , Adolescent , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , COVID-19/pathology , Double-Blind Method , Female , Humans , Lung/pathology , Lung/virology , Male , Middle Aged
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