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1.
Front Pharmacol ; 13: 764305, 2022.
Article in English | MEDLINE | ID: covidwho-1785389

ABSTRACT

Background: To explore the effect of combining traditional Chinese medicine (TCM) and Western medicine in hemodialysis patients with coronavirus disease 2019 (COVID-19). Methods: This study was conducted from 27 January 2020 to 17 March 2020 in Wuhan Third Hospital Guanggu Branch, Wuhan, China. Fifty-three patients were included and divided into a control group (CG), which received Western medicine and a combined treatment group, which received TCM and Western medicine (TG). Clinical and laboratory data, TCM symptom scores, and chest computed tomography results were extracted and compared between the two groups. Results: The TG included 21 (67.7%) men and 10 (32.3%) women with a mean age of 61.02 (standard deviation [SD] 15.07, range 26-89) years. The mean dialysis duration in the TG was 49 (SD 31) months. Of all patients in the TG, 27 (87.1%) had fatigue, 18 (58.1%) had dry cough, 16 (51.6%) had anorexia, 11 (35.5%) had dyspnea, and 11 (35.5%) had fever. The CG included 14 (63.6%) men and 8 (36.4%) women with a mean age of 61.45 (SD 13.78, range 36-84) years. The mean dialysis duration in the CG was 63 (SD 46) months. Of all patients in the CG, 21 (95.5%) had fatigue, 12 (54.5%) had dry cough, 17 (77.3%) had anorexia, 12 (54.5%) had dyspnea, and 7 (31.8%) had fever. After treatment, the TCM symptom scores of the two groups decreased; the anorexia scores were lower in the TG than in the CG (p < 0.05). After treatment, albumin increased and D-dimer, C-reactive protein, and lactate dehydrogenase levels decreased in the TG. The d-dimer levels were lower and the albumin level was higher in the TG than in the CG after treatment (p < 0.05). The cure rate was higher, and the mortality rate was lower in the TG than in the CG (p < 0.05). Conclusion: A combination of TCM and Western medicine in hemodialysis patients with COVID-19 could relieve symptoms and help recovery. Further evidence from larger randomized controlled trials is needed to confirm our results.

2.
Comput Biol Med ; 145: 105509, 2022 06.
Article in English | MEDLINE | ID: covidwho-1778064

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), is a major threat to public health worldwide. Previous studies have shown that the spike protein of SARS-CoV-2 determines viral infectivity and major antigenicity. However, the spike protein has been undergoing various mutations, which bring a great challenge to the prevention and treatment of COVID-19. Here we present the MutCov, a pipeline for evaluating the effect of mutations in spike protein on infectivity and antigenicity of SARS-CoV-2 by calculating the binding free energy between spike protein and angiotensin-converting enzyme 2 (ACE2) or neutralizing monoclonal antibody (mAb). The predicted infectivity and antigenicity were highly consistent with biologically experimental results, and demonstrated that the MutCov achieved good prediction performance. In conclusion, the MutCov is of high importance for systematically evaluating the effect of novel mutations and improving the prevention and treatment of COVID-19. The source code and installation instruction of MutCov are freely available at http://jianglab.org.cn/MutCov.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , COVID-19/genetics , Humans , Mutation , Protein Binding , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308334

ABSTRACT

Objective: Based on the Prevention and Control of COVID-19, this paper points out the shortcomings of China's current medical insurance system, and puts forward the concept of establishing emergency medical insurance system. Methods: : This paper analyzes the characteristics of the modern epidemic and its special requirements for medical insurance. Putting forward the idea of mechanism construction. Results: : The operation of China's national medical insurance system is mainly operated by the insured, the government, medical institutions and medical institutions. However, the rapid spread of the epidemic has caused great disasters to the society. In the face of major public health events, medical insurance should have four characteristics: the "normalization" of the emergency medical insurance system, the fairness of guarantees, the public quality of treatment and positive externalities. China should establish an emergency system in line with these four characteristics from the four parties. Therefore, this paper analyzes the characteristics of modern epidemic risk, its development process and the requirements for the insurance industry in combination with the situation of China's response to dealing with COVID-19, and puts forward that China should further improve the universal medical insurance system and establish an emergency medical security system to better deal with all kinds of sudden public health events, which will still happen in the future. Conclusions: : China's national medical insurance system should not be limited to meet people's conventional medical needs. When public health emergencies occur, it is also necessary to establish a sound medical insurance system to operate.The establishment of emergency medical security system is one of the important development directions of our country in the future.

5.
Front Cell Dev Biol ; 9: 697035, 2021.
Article in English | MEDLINE | ID: covidwho-1367745

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge with Glu329 of hACE2, which resulted in greater electrostatic complementarity, and created a weak salt bridge with Asp442 of RBD. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. The results show consistent with the previous experimental conclusion and clarify the structural mechanism under affinity changes. Our methods will offer guidance on the assessment of the infection efficiency and antigenicity effect of continuing mutations in SARS-CoV-2.

6.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1367012

ABSTRACT

Accurate prediction of immunogenic peptide recognized by T cell receptor (TCR) can greatly benefit vaccine development and cancer immunotherapy. However, identifying immunogenic peptides accurately is still a huge challenge. Most of the antigen peptides predicted in silico fail to elicit immune responses in vivo without considering TCR as a key factor. This inevitably causes costly and time-consuming experimental validation test for predicted antigens. Therefore, it is necessary to develop novel computational methods for precisely and effectively predicting immunogenic peptide recognized by TCR. Here, we described DLpTCR, a multimodal ensemble deep learning framework for predicting the likelihood of interaction between single/paired chain(s) of TCR and peptide presented by major histocompatibility complex molecules. To investigate the generality and robustness of the proposed model, COVID-19 data and IEDB data were constructed for independent evaluation. The DLpTCR model exhibited high predictive power with area under the curve up to 0.91 on COVID-19 data while predicting the interaction between peptide and single TCR chain. Additionally, the DLpTCR model achieved the overall accuracy of 81.03% on IEDB data while predicting the interaction between peptide and paired TCR chains. The results demonstrate that DLpTCR has the ability to learn general interaction rules and generalize to antigen peptide recognition by TCR. A user-friendly webserver is available at http://jianglab.org.cn/DLpTCR/. Additionally, a stand-alone software package that can be downloaded from https://github.com/jiangBiolab/DLpTCR.


Subject(s)
COVID-19/drug therapy , Epitopes/immunology , Peptides/immunology , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Amino Acid Sequence/genetics , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Computer Simulation , Deep Learning , Epitopes/genetics , Humans , Peptides/genetics , Peptides/therapeutic use , Protein Binding/genetics , Receptors, Antigen, T-Cell/genetics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Software
7.
Am J Chin Med ; 49(5): 1063-1092, 2021.
Article in English | MEDLINE | ID: covidwho-1263933

ABSTRACT

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; [Formula: see text]¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; [Formula: see text]¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Drugs, Chinese Herbal/administration & dosage , Aged , COVID-19/pathology , Critical Illness , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Retrospective Studies , Severity of Illness Index
9.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1236217

ABSTRACT

The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients. In this study, we used the single-cell V(D)J sequencing to characterize the BCR repertoire across convalescent COVID-19 patients. We observed that the BCR diversity was significantly reduced in disease compared with healthy controls. And BCRs tend to skew toward different V gene segments in COVID-19 and healthy controls. The CDR3 sequences of heavy chain in clonal BCRs in patients were more convergent than that in healthy controls. In addition, we discovered increased IgG and IgA isotypes in the disease, including IgG1, IgG3 and IgA1. In all clonal BCRs, IgG isotypes had the most frequent class switch recombination events and the highest somatic hypermutation rate, especially IgG3. Moreover, we found that an IgG3 cluster from different clonal groups had the same IGHV, IGHJ and CDR3 sequences (IGHV4-4-CARLANTNQFYDSSSYLNAMDVW-IGHJ6). Overall, our study provides a comprehensive characterization of the BCR repertoire in COVID-19 patients, which contributes to the understanding of the mechanism for the immune response to SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , VDJ Exons/genetics , B-Lymphocytes/immunology , COVID-19/genetics , COVID-19/virology , Female , Humans , Immunoglobulin A/genetics , Immunoglobulin A/immunology , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Male , Receptors, Antigen, B-Cell/immunology , SARS-CoV-2/pathogenicity , Sequence Analysis , Single-Cell Analysis , VDJ Exons/immunology
11.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1062273

ABSTRACT

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Subject(s)
COVID-19/immunology , Megakaryocytes/immunology , Monocytes/immunology , RNA, Viral , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , China , Cohort Studies , Cytokines/metabolism , Female , Humans , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/isolation & purification , Single-Cell Analysis , Transcriptome/immunology , Young Adult
12.
Cell ; 184(3): 775-791.e14, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1014394

ABSTRACT

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.


Subject(s)
COVID-19/metabolism , Gene Expression Regulation , Proteome/biosynthesis , Proteomics , SARS-CoV-2/metabolism , Autopsy , COVID-19/pathology , COVID-19/therapy , Female , Humans , Male , Organ Specificity
13.
Genomics ; 113(2): 456-462, 2021 03.
Article in English | MEDLINE | ID: covidwho-989433

ABSTRACT

T-cell receptor (TCR) is crucial in T cell-mediated virus clearance. To date, TCR bias has been observed in various diseases. However, studies on the TCR repertoire of COVID-19 patients are lacking. Here, we used single-cell V(D)J sequencing to conduct comparative analyses of TCR repertoire between 12 COVID-19 patients and 6 healthy controls, as well as other virus-infected samples. We observed distinct T cell clonal expansion in COVID-19. Further analysis of VJ gene combination revealed 6 VJ pairs significantly increased, while 139 pairs significantly decreased in COVID-19 patients. When considering the VJ combination of α and ß chains at the same time, the combination with the highest frequency on COVID-19 was TRAV12-2-J27-TRBV7-9-J2-3. Besides, preferential usage of V and J gene segments was also observed in samples infected by different viruses. Our study provides novel insights on TCR in COVID-19, which contribute to our understanding of the immune response induced by SARS-CoV-2.


Subject(s)
COVID-19/genetics , High-Throughput Nucleotide Sequencing , Receptors, Antigen, T-Cell/genetics , SARS-CoV-2 , Single-Cell Analysis , COVID-19/immunology , Female , Humans , Male , T-Lymphocytes/immunology
15.
Chin. Trad. Herbal Drugs ; 6(51): 1450-1454, 20200328.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-380429

ABSTRACT

Objective: To analyze the influencing factors of death in patients with coronavirus disease 2019 (COVID-19) and provide a reference for clinically reducing the mortality of patients with COVID-19. Methods: Based on the retrospective analysis of the case data of all patients with COVID-19 admitted in our hospital from January 17th to February 25th, 2020, and the sex, age, whether or not to take Chinese medicine preparations during hospitalization, clinical classification, comorbidities, nucleic acid test results, admission time, discharge and other relevant indicators were collected for statistical analysis. Results: During the period of COVID-19, the number of patients of COVID-19 in our hospital gradually increased. At the epidemic peak period, 904 patients with COVID-19 were treated simultaneously. From January 17th to February 25th, 2020, a total of 1 305 patients with COVID-19 were treated in our hospital, including 632 males and 673 females, and the male to female ratio was 1:1.06. The age distribution ranged from 7 to 111 years, with a median of 63 (51, 70) years old. There was no significant difference in the age distribution of patients between different genders (Z = 1.217, P = 0.224). The results of univariate analysis showed that the patient's gender, age, whether to take Chinese medicine preparations during treatment, clinical classification, whether combined with underlying diseases (hypertension, coronary heart disease, diabetes, tumors and uremia) and nucleic acid test results all could affect patients fatality rate. Logistics multivariate regression analysis found that taking traditional Chinese medicine preparations, clinical classification, and whether combined with underlying diseases were independent risk factors for death in patients with COVID-19. Conclusion: The death of patients with COVID-19 is related to various factors. Reducing the occurrence of critical illness, controlling underlying diseases, stabilizing blood pressure and blood sugar, actively improving cardio-cerebral vascular conditions, and stabilizing renal function are main measures to improve the therapeutic effect, and early application of traditional Chinese medicine treatment also plays a very important role in reducing the mortality of patients with COVID-19.

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