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1.
Journal of Safety Science and Resilience ; 2023.
Article in English | ScienceDirect | ID: covidwho-2311815

ABSTRACT

Crisis information dissemination plays a key role in the development of emergency responses to epidemic-level public health events. Therefore, clarifying the causes of crisis information dissemination and making accurate predictions to effectively control such situations have attracted extensive attention. Based on media richness theory and persuasion theory, this study constructs an index system of crisis information dissemination impact factors from two aspects: the crisis information publisher and the published crisis information content. A multi-layer perceptron is used to analyze the weight of the index system, and the prediction is transformed into a pattern classification problem to test crisis information dissemination. In this study, COVID-19 is considered a representative event. An experiment is conducted to predict the crisis information dissemination of COVID-19 in two megacities. Data related to COVID-19 from these two megacities are acquired from the well-known Chinese social media platform Weibo. The experimental results show that not only the identity but also the social influence of the information publisher has a significant impact on crisis information dissemination in epidemic-level public health events. Furthermore, the proposed model achieves more than 95% test accuracy, precision rate, recall value and f1-score in the prediction task. The study provides decision-making support for government departments and a guide for correctly disseminating crisis information and public opinion during future epidemic-level public health events.

2.
ACS Infect Dis ; 9(5): 1064-1077, 2023 05 12.
Article in English | MEDLINE | ID: covidwho-2304204

ABSTRACT

Entry of enveloped viruses in host cells requires the fusion of viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. These viral fusion proteins need to be triggered by host factors, and for some viruses, this event occurs inside endosomes and/or lysosomes. Consequently, these 'late-penetrating viruses' must be internalized and delivered to entry-conducive intracellular vesicles. Because endocytosis and vesicular trafficking are tightly regulated cellular processes, late-penetrating viruses also depend on specific host proteins for efficient delivery to the site of fusion, suggesting that these could be targeted for antiviral therapy. In this study, we investigated a role for sphingosine kinases (SKs) in viral entry and found that chemical inhibition of sphingosine kinase 1 (SK1) and/or SK2 and knockdown of SK1/2 inhibited entry of Ebola virus (EBOV) into host cells. Mechanistically, inhibition of SK1/2 prevented EBOV from reaching late-endosomes and lysosomes that contain the EBOV receptor, Niemann Pick C1 (NPC1). Furthermore, we present evidence that suggests that the trafficking defect caused by SK1/2 inhibition occurs independently of sphingosine-1-phosphate (S1P) signaling through cell-surface S1P receptors. Lastly, we found that chemical inhibition of SK1/2 prevents entry of other late-penetrating viruses, including arenaviruses and coronaviruses, and inhibits infection by replication-competent EBOV and SARS-CoV-2 in Huh7.5 cells. In sum, our results highlight an important role played by SK1/2 in endocytic trafficking, which can be targeted to inhibit entry of late-penetrating viruses and could serve as a starting point for the development of broad-spectrum antiviral therapeutics.


Subject(s)
Arenavirus , COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Humans , Cell Line , Sphingosine , SARS-CoV-2 , Viral Fusion Proteins
3.
J Biopharm Stat ; 33(4): 476-487, 2023 Jul 04.
Article in English | MEDLINE | ID: covidwho-2286214

ABSTRACT

Defining the right question of interest is important to a clinical study. ICH E9 (R1) introduces the framework of an estimand and its five attributes, which provide a basis for connecting different components of a study with its clinical questions. Most of the applications of the estimand framework focus on efficacy instead of safety assessment. In this paper, we expand the estimand framework into the safety evaluation and compare/contrast the similarity and differences between safety and efficacy estimand. Furthermore, we present and discuss applications of a safety estimand to oncology trials and pooled data analyses. At last, we also discuss the potential usage of safety estimand to handle the impacts of COVID-19 pandemic on safety assessment.


Subject(s)
COVID-19 , Neoplasms , Humans , Research Design , Pandemics , Data Interpretation, Statistical
4.
Computational and mathematical methods in medicine ; 2022, 2022.
Article in English | EuropePMC | ID: covidwho-2045663

ABSTRACT

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide. While COVID-19 generally affects the lungs, it also damages other organs, including those of the cardiovascular system. Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder. Studies have shown that HCM patients with COVID-19 have a higher mortality rate;however, the reason for this phenomenon is not yet elucidated. Herein, we conducted transcriptomic analyses to identify shared biomarkers between HCM and COVID-19 to bridge this knowledge gap. Differentially expressed genes (DEGs) were obtained using the Gene Expression Omnibus ribonucleic acid (RNA) sequencing datasets, GSE147507 and GSE89714, to identify shared pathways and potential drug candidates. We discovered 30 DEGs that were common between these two datasets. Using a combination of statistical and biological tools, protein-protein interactions were constructed in response to these findings to support hub genes and modules. We discovered that HCM is linked to COVID-19 progression based on a functional analysis under ontology terms. Based on the DEGs identified from the datasets, a coregulatory network of transcription factors, genes, proteins, and microRNAs was also discovered. Lastly, our research suggests that the potential drugs we identified might be helpful for COVID-19 therapy.

5.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.08.12.503750

ABSTRACT

Entry of enveloped viruses in host cells requires the fusion of the viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. For fusion, viral fusion proteins need to be triggered by host factors and for some viruses, such as Ebola virus (EBOV) and Lassa fever virus, this event occurs inside endosomes and/or lysosomes. Consequently, these late-penetrating viruses must be internalized and delivered to entry-conducive intracellular vesicles. Because endocytosis and vesicular trafficking are tightly regulated cellular processes, late penetrating viruses also depend on specific host factors, such as signaling molecules, for efficient viral delivery to the site of fusion, suggesting that these could be targeted for antiviral therapy. In this study, we investigated a role for sphingosine kinases (SKs) in viral entry and found that chemical inhibition of sphingosine kinase 1 (SK1) and/or SK2 and knockdown of SK1 or SK2, inhibited entry of EBOV into host cells. Mechanistically, inhibition of SK1 and/or SK2 prevented EBOV from reaching late-endosomes and lysosomes that are positive for the EBOV receptor, Niemann Pick C1 (NPC1). Furthermore, we present evidence that suggests the trafficking defect caused by SK1/2 inhibition occurs independently of S1P signaling through cell-surface S1PRs. Lastly, we found that chemical inhibition of SKs prevents entry of other late-penetrating viruses, including arenaviruses and coronaviruses, in addition to inhibiting infection by replication competent EBOV and SARS-CoV-2 in Huh7.5 cells. In sum, our results highlight an important role played by SKs in endocytic trafficking which can be targeted to inhibit entry of late-penetrating viruses. SK inhibitors could serve as a starting point for the development of broad-spectrum antiviral therapeutics.


Subject(s)
Fever , Hemorrhagic Fever, Ebola
7.
Oxid Med Cell Longev ; 2022: 5397733, 2022.
Article in English | MEDLINE | ID: covidwho-1635531

ABSTRACT

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Apoptosis , COVID-19/immunology , Plasma Cells/immunology , SARS-CoV-2/physiology , Superoxide Dismutase-1/physiology , Adjuvants, Immunologic , Alcoholic Beverages , Alum Compounds , Angiotensin-Converting Enzyme 2/physiology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/enzymology , COVID-19 Vaccines/immunology , Heat-Shock Response , Immunization, Secondary , Immunogenicity, Vaccine , Janus Kinase 2/physiology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress , Plasma Cells/drug effects , Plasma Cells/pathology , Reactive Oxygen Species/metabolism , STAT1 Transcription Factor/physiology , Signal Transduction , Specific Pathogen-Free Organisms , Spike Glycoprotein, Coronavirus/immunology , Vaccination
8.
Journal of multidisciplinary healthcare ; 14:3485-3495, 2021.
Article in English | EuropePMC | ID: covidwho-1602540

ABSTRACT

Purpose This study investigated the association between professional quality of life, working context, and mental health outcomes among hospital personnel in Taiwan during the worldwide upsurge in COVID-19 cases. Patients and Methods We recruited 503 hospital personnel to whom we administered online questionnaires containing items from the Professional Quality of Life (ProQoL) scale, which covers compassion satisfaction (CS), burnout (BO) and compassion fatigue (CF), the Depression, Anxiety and Stress Scale (DASS-21) and questions on work-related variables. Data were collected from 13 July to 19 August 2020. Results The participants generally reported moderate CS and BO and low CF. Overall prevalence of mild-to-extremely-severe stress, anxiety and depression was 24.5%, 39.6% and 31.2%, respectively. Multiple logistic regression revealed that moderate-to-high BO and CF correlated with increased risks of mild-to-extremely-severe stress (OR = 4.17 and 2.23, respectively), anxiety (OR = 4.86 and 2.81, respectively) and depression (OR = 5.83 and 3.01, respectively), while moderate-to-high CS correlated with reduced risks of stress (OR = 0.53) and depression (OR = 0.45) only. There were CS and BO differences in groups categorized by marital status and profession. Anxiety increased linearly by seniority <10, 10–19 and ≥20 years (p for trend <0.05). Conclusion In conclusion, the subscales of ProQOL, BO and CF appeared to be associated with increased risks of stress, anxiety and depression among hospital personnel during the COVID-19 epidemic. A long-term contingency program may be needed to adjust work context variables and support emotional well-being of these workers.

9.
Cell Rep ; 37(3): 109869, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1517084

ABSTRACT

The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.


Subject(s)
Administration, Intranasal , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Bispecific/immunology , COVID-19/immunology , SARS-CoV-2 , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Neutralizing , Antibodies, Viral/immunology , Camelids, New World , Epitopes/chemistry , Female , Humans , Kinetics , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neutralization Tests , Protein Binding , Protein Domains , Protein Engineering/methods , Serum Albumin, Human/chemistry , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus/immunology
10.
Drugs and Clinic ; 35(4):625-630, 2020.
Article in Chinese | GIM | ID: covidwho-1374638

ABSTRACT

Objective: To analyze the utilization of anti-new coronavirus disease 2019 (COVID-19) drugs of inpatients in Hubei N0.3 People's Hospital.

11.
Signal Transduct Target Ther ; 6(1): 300, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1351933

ABSTRACT

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.


Subject(s)
COVID-19/genetics , Diabetes Mellitus/genetics , MicroRNAs/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , Age Factors , Aged , COVID-19/blood , COVID-19/pathology , COVID-19/virology , China , Circulating MicroRNA/blood , Circulating MicroRNA/genetics , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Exercise , Exosomes/genetics , Exosomes/metabolism , Exosomes/virology , Female , Gene Expression Regulation , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , Male , MicroRNAs/blood , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/blood , Virus Replication
12.
J Ethnopharmacol ; 275: 114098, 2021 Jul 15.
Article in English | MEDLINE | ID: covidwho-1164035

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. AIM OF THE STUDY: To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study. MATERIALS AND METHODS: Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1. RESULTS: According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P < 0.0001). CONCLUSION: The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , COVID-19/prevention & control , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , SARS-CoV-2/drug effects , Adult , Animals , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Databases, Genetic , Female , Gene Expression Profiling , Gene Regulatory Networks , Host-Pathogen Interactions , Humans , Male , Middle Aged , Molecular Docking Simulation , Protein Interaction Maps , RNA-Seq , Retrospective Studies , SARS-CoV-2/pathogenicity , Signal Transduction , Transcriptome , Young Adult
13.
CMAJ ; 192(48): E1648-E1656, 2020 Nov 30.
Article in French | MEDLINE | ID: covidwho-1094079

ABSTRACT

CONTEXTE: Les atteintes cardiaques sont fréquentes dans les cas graves de maladie à coronavirus 2019 (COVID-19) et sont associées à un mauvais pronostic. Notre étude portait sur les facteurs prédictifs de mortalité intrahospitalière, les caractéristiques de l'arythmie et les effets des traitements qui allongent l'intervalle QT chez les patients ayant une atteinte cardiaque. MÉTHODES: Nous avons fait une étude de cohorte rétrospective des cas graves de COVID-19 admis à l'hôpital Tongji, à Wuhan, en Chine, entre le 29 janvier et le 8 mars 2020. En examinant ceux qui avaient une atteinte cardiaque, définie ici comme un taux élevé de troponine I cardiaque (TnIc), nous avons déterminé les caractéristiques biologiques et cliniques associées à la mortalité et au besoin de ventilation invasive. RÉSULTATS: Parmi les 1284 cas graves de COVID-19, 1159 avaient au dossier un taux de TnIc mesuré à l'admission, qui pour 170 (14,7 %) participants indiquait une atteinte cardiaque. Les patients ayant une atteinte cardiaque avaient un taux de mortalité nettement plus élevé que les autres patients (71,2 % c. 6,6 %; p < 0,001). Nous avons constaté que le taux de TnIc initial (pour chaque augmentation d'un facteur 10, rapport de risque [HR] 1,32, intervalle de confiance [IC] à 95 % 1,06­1,66) et le taux de TnIc maximal atteint au cours de la maladie (pour chaque augmentation d'un facteur 10, HR 1,70, IC à 95 % 1,38­2,10) étaient associés à de minces chances de survie. Le taux de TnIc maximal était aussi associé au besoin de ventilation invasive (rapport de cotes 3,02, IC à 95 % 1,92­4,98). Sur les 170 patients ayant une atteinte cardiaque, 44 (25,9 %) présentaient une arythmie. Les 6 qui souffraient de tachycardie ou de fibrillation ventriculaires sont morts. Nous avons remarqué que les patients qui recevaient des médicaments allongeant l'intervalle QT avaient un intervalle QTc plus long que ceux qui n'en recevaient pas (différence entre les médianes 45 ms; p = 0,01), mais que ce traitement n'était pas directement lié à la mortalité (HR 1,04, IC à 95 % 0,69­1,57). INTERPRÉTATION: Chez les patients ayant la COVID-19 et une atteinte cardiaque, les taux initial et maximal de TnIc sont associés à de minces chances de survie, et le taux maximal est un facteur prédictif du besoin de ventilation invasive. Les malades de la COVID-19 doivent subir un dépistage des atteintes cardiaques et être surveillés, surtout si on leur fait suivre un traitement qui peut prolonger la repolarisation. Enregistrement de l'essai : Registre des essais cliniques chinois, n° ChiCTR2000031301.

14.
Sci Rep ; 11(1): 3779, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1084610

ABSTRACT

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3-25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hypertension/epidemiology , Multiple Organ Failure/epidemiology , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Treatment Outcome , Post-Acute COVID-19 Syndrome
16.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1066781

ABSTRACT

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.


Subject(s)
COVID-19/metabolism , DNA-Binding Proteins/metabolism , Macrophages/metabolism , Pulmonary Fibrosis/metabolism , Animals , Bleomycin/pharmacology , Carcinoma, Non-Small-Cell Lung/metabolism , Fibrosis , Gene Expression Profiling , Gene Expression Regulation , Humans , Liposomes/chemistry , Lung Diseases, Interstitial/metabolism , Lung Neoplasms/metabolism , Macrophages/virology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Pulmonary Fibrosis/virology , RNA, Small Interfering/metabolism , Scleroderma, Systemic/metabolism , Signal Transduction , Transforming Growth Factor beta1/metabolism
17.
Int J Med Sci ; 18(5): 1198-1206, 2021.
Article in English | MEDLINE | ID: covidwho-1055258

ABSTRACT

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation. Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation. Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients. Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.


Subject(s)
COVID-19/mortality , Critical Illness/mortality , Respiration, Artificial/mortality , Adult , Aged , Aged, 80 and over , COVID-19/therapy , China/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
18.
J Clin Lab Anal ; 35(1): e23654, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-932443

ABSTRACT

BACKGROUND: Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population. METHODS: One hundred and eighty inpatients who were admitted for COVID-19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients. RESULTS: Age (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin-2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high-sensitivity C-reactive protein (p = 0.001), D-dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression. CONCLUSION: Our results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.


Subject(s)
COVID-19/complications , Cardiomyopathies/virology , Aged , Aged, 80 and over , COVID-19/blood , Cardiomyopathies/etiology , Creatine Kinase/blood , Humans , Inflammation Mediators/blood , Killer Cells, Natural , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Myocarditis/etiology , Myocarditis/virology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Risk Factors , Troponin T/blood
19.
Asian Agricultural Research ; 12(8):1-5, 2020.
Article in English | CAB Abstracts | ID: covidwho-914892

ABSTRACT

The COVID-19 epidemic has exerted an impact on the global food supply chain, and also has contributed to the tendency of food hoarding and short supply;strong food demand has led to a rapid rise in international food prices, which has put enormous pressure on China's food import, and domestic food price showed a rise trend accordingly. In order to ensure sufficient and stable supply of China's food market, it is necessary to adhere to the food security strategy of "food self-sufficiency" for a long term. In the spring agricultural production, Shandong Province has taken effective measures to stabilize food production and achieved goad results. It has not been greatly affected by the COVID-19 epidemic;however, under the continuous spread of foreign epidemics, we must adhere to the dual hard core operation of epidemic prevention and production, and explore the establishment of technical specifications for agricultural production under normal conditions for epidemic prevention and control to ensure the food security.

20.
J Med Virol ; 93(4): 2168-2176, 2021 04.
Article in English | MEDLINE | ID: covidwho-871395

ABSTRACT

Hyperglycemia commonly occurs in severe cases with COVID-19. In this study, we explored the associations between admission fasting plasma glucose (FPG) and 28-day mortality in COVID-19 patients. In this single centre retrospective study, 263 adult patients with COVID-19 were included. Demographic and clinical information were collected and compared between patients with and without diabetes. Cox regression analyses were used to investigate the risk factors of 28-day mortality in hospitals. Of 263 patients, 161 (61.2%) were male, 62 (25.6%) had a known history of diabetes, and 135 (51.3%) experienced elevated FPG (>7.0 mmol/L) at hospital admission. The median FPG in patients with diabetes was much higher than in patients without diabetes (12.79 vs. 6.47 mmol/L). Patients with diabetes had higher neutrophil count and D-dimer, less lymphocyte count, lower albumin level, and more fatal complications. Multivariable Cox regression analyses showed that age (per 10-year increase) (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.13-1.74), admission FPG between 7.0 and 11.0 and ≥11.1 mmol/L (HR, 1.90; 95% CI, 1.11-3.25 and HR, 2.09; 95% CI, 1.21-3.64, respectively), chronic obstructive pulmonary disease (HR, 2.89; 95% CI, 1.31-6.39), and cardiac injury (HR, 2.14; 95% CI, 1.33-3.47) were independent predictors of 28-day mortality in COVID-19 patients. Hyperglycemia on admission predicted worse outcome in hospitalized patients with COVID-19. Intensive monitoring and optimal glycemic control may improve the prognosis of COVID-19 patients.


Subject(s)
Blood Glucose/metabolism , COVID-19/blood , COVID-19/mortality , Fasting/blood , Adolescent , Adult , Aged , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Regression Analysis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Survival Analysis , Young Adult
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