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Huanjing yu Zhiye Yixue = Journal of Environmental & Occupational Medicine ; 38(11):1244, 2021.
Article in English | ProQuest Central | ID: covidwho-1604254


[Background] Front-line medical staff are an important group in fighting against Coronavirus Disease 2019 (COVID-19), and their mental health should not be ignored. [Objective] This study investigates the current situation and influencing factors of post-traumatic stress disorder (PTSD) among front-line anti-epidemic medical staff during COVID-19 epidemic. [Methods] Medical staff who had participated in fighting against the COVID-19 epidemic wereselected from three grade III Class A hospitals and four grade II Class A hospitals in a city of Hubei Province by convenient sampling method in May 2020. The survey was conducted online using the Post-traumatic Stress Checklist-Civilian Version (PCL-C) as the main survey tool to investigate current situation and characteristics of PTSD among these participants. A total of 1120 questionnaires were collected, of which 1071 were valid, and the effective rate was 95.6%. [Results] Of the 1071 participants, the average age was (32.59±5.21) years;the ratio of male to female was 1: 5.02;the ratio of doctor to nurse was 1:5.8;nearly 70% participants came from grade III Class A hospitals;married participants accounted for 75.4%;most of them held a bachelor degree or above (86.5%);members of the Communist Party of China (CPC) accounted for 22.9%;50.9% had junior titles;the working years were mainly 5−10 years (42.8%);more than 80.0% participants volunteered to join the front-line fight;95.1% participants received family support;43.0% participated in rescue missions;78.1% participants fought the epidemic in their own hospitals;more than 60% participants considered the workload was greater than before;34.4% participants fought in the front-line for 2−4 weeks, and 23.5% participants did for more than 6 weeks. There were 111 cases of positive PTSD syndromes (PCL-C total score ≥38) with an overall positive rate of 10.4%, and the scores of reexperience [1.40 (1.00, 1.80)] and hypervigilance [1.40 (1.00, 2.00)] were higher than the score of avoidance [1.14 (1.00, 2.57)]. The results of univariate analysis revealed that PTSD occurred differently among participants grouped by age, political affiliation, working years, anti-epidemic activities location, accumulated working hours in fighting against COVID-19, having child parenting duty, voluntariness, family support, whether family members participated in front-line activities, and rescue mission assignment (P<0.05). The results of logistic regression analysis showed that the incidence rates of reporting PTSD syndromes in medical personnel aged 31−40 years (OR=0.346, 95%CI: 0.164−0.730) and aged 41 years and above (OR=0.513, 95%CI: 0.319-0.823) were lower than that in those aged 20−30 years;the incidence rates of reporting PTSD syndromes in medical staff who were CPC members (OR=0.499, 95%CI: 0.274−0.909), volunteered to participate (OR=0.584, 95%CI: 0.360−0.945), and received family support (OR=0.453, 95%CI: 0.222-0.921) were lower than those did not (P<0.05);the incidence rates of reporting PTSD syndromes among medical workers who had child parenting duty (OR=2.372, 95%CI: 1.392−4.042), whose family members participated in front-line activities (OR=1.709, 95%CI: 1.135−2.575), and who participated in rescue missions (OR=1.705, 95%CI: 1.133-2.565) were higher than those who did not (P<0.05). [Conclusion] The positive PTSD syndrome rate is 10.4% in the front-line anti-epidemic medical staff. Age, political affiliation, voluntariness, family support, having child parenting duty, with a family members participating in the fight, and rescue mission assignment are the influencing factors of PTSD.

Blood ; 136(Supplement 1):29-30, 2020.
Article in English | PMC | ID: covidwho-1339113


Background and Rationale Patients with multiple myeloma (MM) are at a higher risk of viral infection due to immune deficiency. Importantly, recent studies highlighted the severity of COVID-19 in MM. To date, however, the mechanism(s) underlying the lack of anti-viral immune response in MM are unclear. Plasmacytoid dendritic cells (pDCs) play a key role in both recognition of viral nucleic acid and initiating anti-viral activity via type 1 interferon (IFN) response signaling. We showed that interactions of dysfunctional pDCs with MM cells, T cells, and NK cells confer immune suppression in the host-MM bone marrow (BM) microenvironment (Chauhan et al, Cancer Cell 2009;16: p309;Ray et al, Leukemia 2015;29: p1441). Here, we analyzed the immune-pathway proteins implicated in Covid-19-host interactions [Gordon et al, Nature 2020;583, p459] to assess whether pDC-MM interactions modulate these pathways to confer immune suppression and susceptibility to COVID-19. We identified the TLR pathway serine/threonine kinase TBK1 (TANK-binding kinase 1), involved in type I IFN induction, as a potential immunotherapeutic target in MM. Moreover, Covid-19 relies on host-Ubiquitin-proteasome-system for propagation, and we found that targeting ubiquitin receptor Rpn13 with a specific inhibitor RA190 restores TBK1 expression in MM.Methods For our studies, we examined SARS-CoV-2-human protein-protein interactions (PPIs) maps (Gordon et al, 2020). pDC-MM co-cultures, and RNAseq using next- generation sequencing (NGS): Purified MM patient pDCs were cocultured with autologous MM cells (1pDC/5MM) for 48h, followed by separation of MM cells from pDCs using FACS. Total RNA from MM cells was subjected to RNAseq analysis using Illumina NGS. Raw sequence data were analyzed to generate differential expression (DEseq2). Linear model (Limma) and its GUI (Glimma) were also used. Statistical significance: log2FC (fold change) values in coculture vs control, with a False Discovery Rate value of <0.05, was considered significant (CI >95). The heatmap analysis was done using Morpheus software (Broad Institute, MIT). MM patient and pDCs data used for bioinformatics were from the NCBI GEO.Results A total of 41 genes involved in the Covid-19 host-pathogen immune interactions are also differentially expressed in MM after coculture with pDCs. (log2Fold change: ± 3.5-fold;p <0.00001;pDC-MM vs MM alone). The gene expression widely varies in pDC-MM vs MM [Median (log10): -0.13 to 4.5;adj p <0.001]. We identified 3 specific innate immunity-linked genes TBK1, IRF3 (Interferon regulatory factor 3), and RAE1 (interferon-inducible mRNA nuclear export factor) which are essential for IFN production in MM. Importantly, pDCs decrease TBK1 (Log2FC: -0.5) and RAE1 (Log2FC: -0.3) as well as induce IRF3 (Log2FC: 1.5) in MM (p <0.0001). Analysis of publicly available gene profiling datasets on relapsed MM patient showed low levels of TBK1 and RAE1 and higher IRF3 (n = 50) [Log2FC: TBK1: -0.208;RAE1: -0.286;IRF3: 0.273;vs normal;p <0.05). Of note, low TBK1 expression correlates with poor survival in MM patients (n = 350) and elevated TBK1 correlates with a better prognosis (p = 0.026). Similar analysis showed that most of 41 genes involved in the Covid-19 host-pathogen immune interactions are expressed in pDCs. In unstimulated pDCs, TBK1 expression is significantly lower than IRF3 and RAE1 (2-3-fold, p <0.05). In functional studies, treatment of pDCs with IFN-α activating CpG-ODN type-A increases both TBK1 (adj P = 0.004) and RAE1 (adj P = 0.043), without significantly altering IRF3 expression. Taken together, we show that TBK1 is downregulated in pDCs, and pDCs-MM interactions further decreases TBK1 in MM, thereby attenuating IFN-mediated anti-viral immune response signaling in MM. Finally, we found that blockade of proteasome-mediated protein degradation via inhibition of Ubiquitin receptor Rpn13 upregulates TBK-1 expression, indicating potential clinical use of targeting Rpn13 in restoring anti-viral immune responses in MM.Conclusion We ound that pDC-MM interactions downregulate TBK1, which in turn reduces IFN response signaling essential to generate an effective anti-viral immune response in the MM BM microenvironment. Our findings suggest that: 1) low levels of TBK1 may confer increased susceptibility of MM patients to COVID-19;and 2) targeting TBK1 may restore anti-viral immune response and reduce COVID-19 severity in MM.

Bioconjug Chem ; 31(11): 2553-2563, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-872629


As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, Au@Ag nanorods (Au@AgNRs) were successfully synthesized by coating AuNRs with silver and were shown for the first time to have activity against the replication of porcine epidemic diarrhea virus (PEDV). Viral titer analysis demonstrated that Au@AgNRs could inhibit PEDV infection by 4 orders of magnitude at 12 h post-infection, which was verified by viral protein expression analysis. The potential mechanism of action showed that Au@AgNRs could inhibit the entry of PEDV and decrease the mitochondrial membrane potential and caspase-3 activity. Additionally, we demonstrated that a large amount of virus proliferation can cause the generation of reactive oxygen species in cells, and the released Ag+ and exposed AuNRs by Au@AgNRs after the stimulation of reactive oxygen species has superior antiviral activity to ensure long-term inhibition of the PEDV replication cycle. The integrated results support that Au@AgNRs can serve as a potential therapeutic strategy to prevent the replication of coronavirus.

Gold/chemistry , Gold/pharmacology , Metal Nanoparticles/chemistry , Porcine epidemic diarrhea virus/drug effects , Porcine epidemic diarrhea virus/physiology , Silver/chemistry , Virus Replication/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/toxicity , Chlorocebus aethiops , Dose-Response Relationship, Drug , Gold/toxicity , Nanotubes/chemistry , Vero Cells