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1.
Oxidative medicine and cellular longevity ; 2022, 2022.
Article in English | EuropePMC | ID: covidwho-1837179

ABSTRACT

The purpose of this research was to explore the underlying biological processes causing coronavirus disease 2019- (COVID-19-) related stroke. The Gene Expression Omnibus (GEO) database was utilized to obtain four COVID-19 datasets and two stroke datasets. Thereafter, we identified key modules via weighted gene co-expression network analysis, following which COVID-19- and stroke-related crucial modules were crossed to identify the common genes of COVID-19-related stroke. The common genes were intersected with the stroke-related hub genes screened via Cytoscape software to discover the critical genes associated with COVID-19-related stroke. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common genes associated with COVID-19-related stroke, and the Reactome database was used to annotate and visualize the pathways involved in the key genes. Two COVID-19-related crucial modules and one stroke-related crucial module were identified. Subsequently, the top five genes were screened as hub genes after visualizing the genes of stroke-related critical module using Cytoscape. By intersecting the COVID-19- and stroke-related crucial modules, 28 common genes for COVID-19-related stroke were identified. ITGA2B and ITGB3 have been further identified as crucial genes of COVID-19-related stroke. Functional enrichment analysis indicated that both ITGA2B and ITGB3 were involved in integrin signaling and the response to elevated platelet cytosolic Ca2+, thus regulating platelet activation, extracellular matrix- (ECM-) receptor interaction, the PI3K-Akt signaling pathway, and hematopoietic cell lineage. Therefore, platelet activation, ECM-receptor interaction, PI3K-Akt signaling pathway, and hematopoietic cell lineage may represent the potential biological processes associated with COVID-19-related stroke, and ITGA2B and ITGB3 may be potential intervention targets for COVID-19-related stroke.

2.
Vaccines ; 10(5):647, 2022.
Article in English | MDPI | ID: covidwho-1792356

ABSTRACT

As the third year of the global COVID-19 pandemic, vaccination remains the most effective tool against infections and symptomatic illness. Comprehension regarding immunity to SARS-CoV-2 is limited, and the durability of immune responses after vaccination is currently not clear. In this study, we randomly collected 395 questionnaires to analyze the current state of COVID-19 vaccination. At the same time, the serum of 16 individuals who had received two doses of the COVID-19 vaccine were collected at different times before and after the booster vaccination. We analyzed the dynamic changes of SARS-CoV-2 S-specific binding antibodies in serum and immunological indicators. By collecting public opinion surveys and analyzing variational trends of SARS-CoV-2 S-specific binding antibodies and immune indicators after COVID-19 booster vaccination, we endeavored to demonstrate the concerns affecting people's booster vaccinations, as well as the frequency, timing, and necessity of COVID-19 booster vaccinations. The analysis of antibody results in 16 vaccinated volunteers showed that the antibody concentration decreased six months after the second dose and the protective effect of the virus was reduced. The third dose of COVID-19 vaccination is necessary to maintain the antibody concentration and the protective effect of the virus. The vaccination with the vaccine booster depends not only on the time interval but also on the initial concentration of the SARS-CoV-2 S-specific binding antibody before the booster. Our study has important implications for raising public awareness of vaccinating against SARS-CoV-2 and the necessity of COVID-19 booster vaccinations.

3.
Res Sq ; 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1786500

ABSTRACT

The COVID-19 pandemic spurred a broad interest in antiviral drug discovery. The SARS-CoV-2 main protease (M pro ) and papain-like protease (PL pro ) are attractive antiviral drug targets given their vital roles in viral replication and modulation of host immune response. Structurally disparate compounds were reported as M pro and PL pro inhibitors from either drug repurposing or rational design. Two polyphenols dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) were recently reported as SARS-CoV-2 main protease (M pro ) inhibitors. With our continuous interest in studying the mechanism of inhibition and resistance of M pro inhibitors, we report herein our independent validation/invalidation of these two natural products. Our FRET-based enzymatic assay showed that neither dieckol nor PGG inhibited SARS-CoV-2 M pro (IC 50 > 20 µM), which is in contrary to previous reports. Serendipitously, PGG was found to inhibit the SARS-CoV-2 papain-like protease (PL pro ) with an IC 50 of 3.90 µM. The binding of PGG to PL pro was further confirmed in the thermal shift assay. However, PGG was cytotoxic in 293T-ACE2 cells (CC 50 = 7.7 µM), so its intracellular PL pro inhibitory activity could not be quantified by the cell-based Flip-GFP PL pro assay. In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PL pro inhibitors using the Flip-GFP assay. Overall, our results call for stringent hit validation, and the serendipitous discovery of PGG as a putative PL pro inhibitor might worth further pursuing.

4.
ACS Infect Dis ; 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1783938

ABSTRACT

The global COVID-19 pandemic underscores the dire need for effective antivirals. Encouraging progress has been made in developing small-molecule inhibitors targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). However, the development of papain-like protease (PLpro) inhibitors faces several obstacles. Nevertheless, PLpro represents a high-profile drug target given its multifaceted roles in viral replication. PLpro is involved in not only the cleavage of viral polyprotein but also the modulation of host immune response. In this study, we conducted a drug-repurposing screening of PLpro against the MedChemExpress bioactive compound library and identified three hits, EACC, KY-226, and tropifexor, as potent PLpro inhibitors with IC50 values ranging from 3.39 to 8.28 µM. The three hits showed dose-dependent binding to PLpro in the thermal shift assay. In addition, tropifexor inhibited the cellular PLpro activity in the FlipGFP assay with an IC50 of 10.6 µM. Gratifyingly, tropifexor showed antiviral activity against SARS-CoV-2 in Calu-3 cells at noncytotoxic concentrations. Overall, tropifexor represents a novel PLpro inhibitor that can be further developed as SARS-CoV-2 antivirals.

5.
Zhongguo Fei Ai Za Zhi ; 25(3): 147-155, 2022 Mar 20.
Article in Chinese | MEDLINE | ID: covidwho-1780097

ABSTRACT

BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS: The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.


Subject(s)
Adenocarcinoma of Lung , Anaplastic Lymphoma Kinase , Lung Neoplasms , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/genetics , Aged , Anaplastic Lymphoma Kinase/genetics , ErbB Receptors/genetics , Female , Genes, erbB-1 , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Tomography, X-Ray Computed/methods
6.
Front Surg ; 9: 853441, 2022.
Article in English | MEDLINE | ID: covidwho-1776104

ABSTRACT

Aim: Limited data are available on the impact of the coronavirus disease 2019 (COVID-19) pandemic on patient-reported outcome measures (PROMs) in patients who underwent spine surgery. In this study, we aimed to investigate the associations between the COVID-19 outbreak in Taiwan (May 2021) and PROMs in patients who underwent spine surgery. Method: We retrospectively identified patients who underwent spine surgery during identical defined 6-week time-intervals (May 16 to June 30) in 2019, 2020, and 2021. PROMs, including visual analog scale (VAS) score for pain, Oswestry disability index (ODI), and EuroQol-5D (EQ-5D), were investigated before surgical intervention and at a 1-month follow-up. Relevant clinical information was collected from the electronic medical records of patients. Linear regression analysis was used to examine the association between the pandemic in 2021 (vs. 2019/2020) and the PROMs after adjusting for age, sex, and relevant clinical variables. Results: The number of patients who underwent spine surgery at our hospital during the identical defined 6-week time-intervals in 2019, 2020, and 2021 was 77, 70, and 48, respectively. The surgical intervention significantly improved VAS, ODI, and EQ-5D of the patients (1 month after surgery vs. before surgery, all p < 0.001) in all three study periods. However, there was a significant between-group difference in change from baseline in VAS (p = 0.002) and EQ-5D (p = 0.010). The decrease in VAS and increase in EQ-5D after surgery in 2021 were not as much as those in 2019 and 2020. The associations between the pandemic in 2021 (vs. 2019/2020) and changes in VAS (ß coefficient 1.239; 95% confidence interval [CI] 0.355 to 2.124; p = 0.006) and EQ-5D (ß coefficient, -0.095; 95% CI, -0.155 to -0.035; p = 0.002) after spine surgery were independent of relevant clinical factors. Conclusion: There was less improvement in short-term PROMs (VAS and EQ-5D) after spine surgery during the COVID-19 pandemic. Assessment of PROMs in surgical patients during a pandemic may be clinically relevant, and psychological support in this condition might help improve patients' outcomes.

7.
Psychol Res Behav Manag ; 15: 777-784, 2022.
Article in English | MEDLINE | ID: covidwho-1770853

ABSTRACT

Purpose: This study aims to evaluate the psychological status and the attitudes toward the novel coronavirus disease 2019 (COVID-19) vaccine among anesthesiologists. We expected to analyze related factors and offer them some strategies to prevent and manage psychological issues under the post COVID-19 era. Methods: Based on the Checklist for Reporting Results of Internet E-Surveys (CHERRIES), an online survey was designed and conducted among anesthesiologists in Shaanxi, China. Participants were asked to complete a validated questionnaire voluntarily. The following tests were performed: Depression, Anxiety and Stress Scale (DASS-21), Primary Care Post-traumatic Stress Disorder Screen (PC-PTSD), and the attitudes toward COVID-19 vaccine. Results: A total of 795 anesthesiologists completed the survey, the majority of them were female, young and middle-aged, well educated, and married. The prevalence of depression, anxiety, and stress in this sample were 26.5%, 35.5%, and 19.9%, respectively. Longer daily working time, concomitant basic chronic disease, and COVID-19 exposure were extracted as risk factors for the psychological symptoms, while vaccination, elder age, and married status were negatively associated with them. An unsatisfied vaccination rate (71.9%) which might be linked with inadequate awareness and perception of the COVID-19 vaccine was also detected in this study. Conclusion: Anesthesiologists are still under rising pressure of psychological symptoms in the post COVID-19 era. It is imperative to afford continuous psychological support to them and ensure their mental health and professional performance.

8.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331809

ABSTRACT

The COVID-19 pandemic spurred a broad interest in antiviral drug discovery. The SARS-CoV-2 main protease (M pro ) and papain-like protease (PL pro ) are attractive antiviral drug targets given their vital roles in viral replication and modulation of host immune response. Structurally disparate compounds were reported as M pro and PL pro inhibitors from either drug repurposing or rational design. Two polyphenols dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) were recently reported as SARS-CoV-2 main protease (M pro ) inhibitors. With our continuous interest in studying the mechanism of inhibition and resistance of M pro inhibitors, we report herein our independent validation/invalidation of these two natural products. Our FRET-based enzymatic assay showed that neither dieckol nor PGG inhibited SARS-CoV-2 M pro (IC 50 > 20 µM), which is in contrary to previous reports. Serendipitously, PGG was found to inhibit the SARS-CoV-2 papain-like protease (PL pro ) with an IC 50 of 3.90 µM. The binding of PGG to PL pro was further confirmed in the thermal shift assay. However, PGG was cytotoxic in 293T-ACE2 cells (CC 50 = 7.7 µM), so its intracellular PL pro inhibitory activity could not be quantified by the cell-based Flip-GFP PL pro assay. In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PL pro inhibitors using the Flip-GFP assay. Overall, our results call for stringent hit validation, and the serendipitous discovery of PGG as a putative PL pro inhibitor might worth further pursuing.

9.
Jpn J Radiol ; 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1763448

ABSTRACT

PURPOSE: To spotlight the trends and hot topics looming from the highly cited papers in the subject category of Radiology, Nuclear Medicine & Medical Imaging with bibliometric analysis. MATERIALS AND METHODS: Based on the Essential Science Indicators, this study employed a bibliometric method to examine the highly cited papers in the subject category of Radiology, Nuclear Medicine & Medical Imaging in Web of Science (WoS) Categories, both quantitatively and qualitatively. In total, 1325 highly cited papers were retrieved and assessed spanning from the years of 2011 to 2021. In particular, the bibliometric information of the highly cited papers based on WoS database such as the main publication venues, the most productive countries, and the top cited publications was presented. An Abstract corpus was built to help identify the most frequently explored topics. VoSviewer was used to visualize the co-occurrence networks of author keywords. RESULTS: The top three active journals are Neuroimage, Radiology and IEEE T Med Imaging. The United States, Germany and England have the most influential publications. The top cited publications unrelated to COVID-19 can be grouped in three categories: recommendations or guidelines, processing software, and analysis methods. The top cited publications on COVID-19 are dominantly in China. The most frequently explored topics based on the Abstract corpus and the author keywords with the great link strengths overlap to a great extent. Specifically, phrases such as magnetic resonance imaging, deep learning, prostate cancer, chest CT, computed tomography, CT images, coronavirus disease, convolutional neural network(s) are among the most frequently mentioned. CONCLUSION: The bibliometric analysis of the highly cited papers provided the most updated trends and hot topics which may provide insights and research directions for medical researchers and healthcare practitioners in the future.

10.
J Control Release ; 345: 494-511, 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1756278

ABSTRACT

Abnormal immune cell functions are commonly related to various diseases, including cancer, autoimmune diseases, and infectious diseases. Messenger RNA (mRNA)-based therapy can regulate the functions of immune cells or assign new functions to immune cells, thereby generating therapeutic immune responses to treat these diseases. However, mRNA is unstable in physiological environments and can hardly enter the cytoplasm of target cells; thus, effective mRNA delivery systems are critical for developing mRNA therapy. The two mRNA vaccines of Pfizer-BioNTech and Moderna have demonstrated that lipid nanoparticles (LNPs) can deliver mRNA into dendritic cells (DCs) to induce immunization against severe acute respiratory syndrome coronavirus 2, which opened the floodgates to the development of mRNA therapy. Apart from DCs, other immune cells are promising targets for mRNA therapy. This review summarized the barriers to mRNA delivery and advances in mRNA delivery for regulating the functions of different immune cells.

11.
Acta Pharm Sin B ; 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1756265

ABSTRACT

Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

12.
Am J Orthod Dentofacial Orthop ; 2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1748312

ABSTRACT

INTRODUCTION: Orthodontic students need to accurately identify cephalometric landmarks to perform cephalometric measurements, which is the prerequisite to proper orthodontic diagnosis and treatment. To provide insights into future cephalometric education, we compared the performance of different methods that can be used in tracing practice, including a novel online game-based method, the cephalometric training module of Uceph (version 948; Uceph, Chengdu, China). METHODS: A total of 45 first-year orthodontic graduate students were divided into 3 groups to receive different kinds of cephalometric training (module group, practicing with the cephalometric training module of Uceph; teaching group, practicing under the teacher's guidance; self-training group, practicing with traced cephalogram as reference). After training with 4 cephalograms, students completed 2 test samples in which the tracing accuracy and time were recorded and a questionnaire concerning their feelings. RESULTS: Both the teaching and module group offered performance advantages on increasing the tracing accuracy and speed of students. The module group provided a better performance on improving tracing accuracy than the teaching group. Students in the module group showed improved concentration, interest, satisfaction toward the teaching method and confidence of correctly identifying landmarks than self-training group, and enhanced interest than students in the teaching group. CONCLUSIONS: The shooting game-based cephalometric training module of Uceph has demonstrated better performance than traditional face-to-face teaching and self-learning, proving to be a viable online tool to train cephalometric tracing, especially during the coronavirus disease 2019 pandemic.

14.
J Genet Genomics ; 48(9): 792-802, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1720311

ABSTRACT

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.


Subject(s)
Gastrointestinal Microbiome/physiology , Inflammation/metabolism , COVID-19/microbiology , Dysbiosis/microbiology , Gastrointestinal Microbiome/genetics , Humans , Inflammation/genetics , Proteomics/methods
15.
Bio Protoc ; 12(3): e4314, 2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1716345

ABSTRACT

Coronaviruses are important human pathogens, among which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic. To combat the SARS-CoV-2 pandemic, there is a pressing need for antivirals, especially broad-spectrum antivirals that are active against all seven human coronaviruses (HCoVs). For this reason, we are interested in developing antiviral assays to expedite the drug discovery process. Here, we provide the detailed protocol for the cytopathic effect (CPE) assay and the plaque assay for human coronaviruses 229E (HCoV-229E), HCoV-OC43, and HCoV-NL63, to identify novel antivirals against HCoVs. Neutral red was used in the CPE assay, as it is relatively inexpensive and more sensitive than other reagents. Multiple parameters including multiplicity of infection, incubation time and temperature, and staining conditions have been optimized for CPE and plaque assays for HCoV-229E in MRC-5, Huh-7, and RD cell lines; HCoV-OC43 in RD, MRC-5, and BSC-1 cell lines, and HCoV-NL63 in Vero E6, Huh-7, MRC-5, and RD cell lines. Both CPE and plaque assays have been calibrated with the positive control compounds remdesivir and GC-376. Both CPE and plaque assays have high sensitivity, excellent reproducibility, and are cost-effective. The protocols described herein can be used as surrogate assays in the biosafety level 2 facility to identify entry inhibitors and protease inhibitors for SARS-CoV-2, as HCoV-NL63 also uses ACE2 as the receptor for cell entry, and the main proteases of HCoV-OC43 and SARS-CoV-2 are highly conserved. In addition, these assays can also be used as secondary assays to profile the broad-spectrum antiviral activity of existing SARS-CoV-2 drug candidates.

16.
Front Pharmacol ; 13: 817793, 2022.
Article in English | MEDLINE | ID: covidwho-1705160

ABSTRACT

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

17.
iScience ; 2022.
Article in English | EuropePMC | ID: covidwho-1695175

ABSTRACT

Clotting Factor V (FV) is primarily synthesised in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes and T regulatory cells as sources of increased FV in hospitalised patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system. Graphical

18.
iScience ; 25(3): 103971, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1699877

ABSTRACT

Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324511

ABSTRACT

Background: Corona Virus Disease 2019 (COVID-19) is a recently emerged life-threatening disease caused by SARS-CoV-2. It has the characteristics of rapid transmission, difficult treatment, rapid deterioration, and high mortality rate. Reliable and rapid diagnosis of SARS-CoV-2 infection is critical to treat patients and control transmission in time. Methods To detect SARS-CoV-2 nucleic acid faster and more convenient, RT-LAMP method (reverse transcription loop-mediated isothermal amplification) was developed. ORF1ab gene, E gene and N gene were selected as the target genes, because ORF1ab gene is the most specific and N gene is the most sensitive, while E gene has both sensitivity and specificity. Over thirty primer sets for them were designed, then the primer sets with rapid response and high specificity were screened out and their loop primers were designed and selected in order to improve the reaction speed further. Using these primers, RNA reverse transcription and nucleic acid amplification were performed in one step at 63 ℃ isothermal conditions, and the results can be judged by naked eyes through color change within 30 minutes. Finally, the optimal primer set for each gene was verified with over 208 clinical samples. Results ORF1ab gene, E gene and N gene were detected simultaneously by this method. ORF1ab gene has high specificity and the same sensitivity as RT-PCR currently used in clinic. Although N gene is less specific than ORF1ab, it is 80 times more sensitive than ORF1ab. The sensitivity and specificity of E gene are between them. Simultaneous detection of these three genes can neither cause false positives nor miss samples with low virus concentration, ensuring the sensitivity and specificity of SARS-CoV-2 detection. BLAST comparing results showed the primers for the three genes were highly specific for SARS-CoV-2. And the sequencing results of RT-LAMP products showed that the amplified fragments were unique to SARS-CoV-2. The accuracy of RT-LAMP assay was 99% as detecting 208 clinical specimens. Conclusions The RT-LAMP assay reported here has the advantages of rapid amplification, simple operation, and easy detection, which is useful for the rapid and reliable clinical diagnosis of SARS-CoV-2.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324417

ABSTRACT

New coronavirus disease (COVID-19) has constituted a global pandemic and has spread to most countries and regions in the world. By understanding the development trend of a regional epidemic, the epidemic can be controlled using the development policy. The common traditional mathematical differential equations and population prediction models have limitations for time series population prediction, and even have large estimation errors. To address this issue, we propose an improved method for predicting confirmed cases based on LSTM (Long-Short Term Memory) neural network. This work compared the deviation between the experimental results of the improved LSTM prediction model and the digital prediction models (such as Logistic and Hill equations) with the real data as reference. And this work uses the goodness of fitting to evaluate the fitting effect of the improvement. Experiments show that the proposed approach has a smaller prediction deviation and a better fitting effect. Compared with the previous forecasting methods, the contributions of our proposed improvement methods are mainly in the following aspects: 1) we have fully considered the spatiotemporal characteristics of the data, rather than single standardized data;2) the improved parameter settings and evaluation indicators are more accurate for fitting and forecasting. 3) we consider the impact of the epidemic stage and conduct reasonable data processing for different stage.

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