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1.
Front Immunol ; 12: 697622, 2021.
Article in English | MEDLINE | ID: covidwho-1518482

ABSTRACT

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported. Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset. Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR-CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers. Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Adaptive Immunity , Aged , Aged, 80 and over , Antibodies, Viral/blood , B-Lymphocytes/immunology , COVID-19/blood , COVID-19/classification , COVID-19/physiopathology , Cytokines/blood , Dendritic Cells/immunology , Female , Humans , Immunity, Innate , Immunoglobulin G/blood , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , SARS-CoV-2/immunology , Severity of Illness Index , T-Lymphocytes/immunology
2.
International Journal of Infectious Diseases ; 95:436-440, 2020.
Article in English | CAB Abstracts | ID: covidwho-1409652

ABSTRACT

Background: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice.

3.
Front Med (Lausanne) ; 7: 374, 2020.
Article in English | MEDLINE | ID: covidwho-646639

ABSTRACT

Background: The predictive value of prealbumin for the prognosis of coronavirus disease 2019 (COVID-19) has not been extensively investigated. Methods: A total of 1,115 patients with laboratory-confirmed COVID-19 were enrolled at Tongji hospital from February to April 2020 and classified into fatal (n = 129) and recovered (n = 986) groups according to the patient's outcome. Prealbumin and other routine laboratory indicators were measured simultaneously. Results: The level of prealbumin on admission was significantly lower in fatal patients than in recovered patients. For predicting the prognosis of COVID-19, the performance of prealbumin was better than most routine laboratory indicators, such as albumin, lymphocyte count, neutrophil count, hypersensitive C-reactive protein, d-dimer, lactate dehydrogenase, creatinine, and hypersensitive cardiac troponin I. When a threshold of 126 mg/L was used to discriminate between fatal and recovered patients, the sensitivity and specificity of prealbumin were, respectively, 78.29 and 90.06%. Furthermore, a model based on the combination of nine indexes showed an improved performance in predicting the death of patients with COVID-19. Using a cut-off value of 0.19, the prediction model was able to distinguish between fatal and recovered individuals with a sensitivity of 86.82% and a specificity of 90.37%. Conclusions: A lower level of prealbumin on admission may indicate a worse outcome of COVID-19. Immune and nutritional status may be vital factors for predicting disease progression in the early stage of COVID-19.

4.
J Clin Immunol ; 40(7): 960-969, 2020 10.
Article in English | MEDLINE | ID: covidwho-641161

ABSTRACT

BACKGROUND: There are currently rare satisfactory markers for predicting the death of patients with coronavirus disease 2019 (COVID-19). The aim of this study is to establish a model based on the combination of serum cytokines and lymphocyte subsets for predicting the prognosis of the disease. METHODS: A total of 739 participants with COVID-19 were enrolled at Tongji Hospital from February to April 2020 and classified into fatal (n = 51) and survived (n = 688) groups according to the patient's outcome. Cytokine profile and lymphocyte subset analysis was performed simultaneously. RESULTS: The fatal patients exhibited a significant lower number of lymphocytes including B cells, CD4+ T cells, CD8+ T cells, and NK cells and remarkably higher concentrations of cytokines including interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor-α on admission compared with the survived subjects. A model based on the combination of interleukin-8 and the numbers of CD4+ T cells and NK cells showed a good performance in predicting the death of patients with COVID-19. When the threshold of 0.075 was used, the sensitivity and specificity of the prediction model were 90.20% and 90.26%, respectively. Meanwhile, interleukin-8 was found to have a potential value in predicting the length of hospital stay until death. CONCLUSIONS: Significant increase of cytokines and decrease of lymphocyte subsets are found positively correlated with in-hospital death. A model based on the combination of three markers provides an attractive approach to predict the prognosis of COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/mortality , Cytokines/blood , Lymphocyte Subsets/immunology , Models, Biological , Pneumonia, Viral/mortality , Aged , Aged, 80 and over , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Biomarkers/blood , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques/methods , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cytokines/immunology , Female , Humans , Length of Stay , Lymphocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Prognosis , RNA, Viral/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Risk Assessment/methods , SARS-CoV-2
5.
Chin. Trad. Herbal Drugs ; 7(51): 1804-1813, 20200412.
Article in Chinese | ELSEVIER | ID: covidwho-258232

ABSTRACT

Objective: To explore the main active components, key targets and signaling pathways of Qingfei Dayuan Granules in treating of COVID-19 based on network pharmacology and molecular docking. Methods: TCMSP, ETCM and YATCM databases were used to search the chemical constituents of Qingfei Dayuan Granules, and the threshold values of OB ≥ 30% and DL ≥0.18 were used to screen the potential active compounds. SIB and STITCH databases were used to query the targets corresponding to the active compounds, and the PPI network and network topology parameters were obtained by using STRING database. Cytoscape 3.6.0 was used to screen the hub targets. The key targets were analyzed by Gene Ontology (GO), the Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment and tissue enrichment using DAVID 6.8 software. The molecular docking was performed by AutoDock Tools 1.5.6 software. Results: A total of 251 active compounds and 1 037 targets were obtained, 107 key targets and 185 corresponding compounds were screened. The key targets involved ESR1, AR, EGFR, KDR, MMP2, and 52 genes were coexpressed with ACE2. The results of GO function enrichment analysis showed that Qingfei Dayuan Granules mainly regulated the biological processes of cell surface signaling transduction, molecular function, phosphorylation and transcription. KEGG pathway enrichment mainly involved chemokine signaling pathway, T cell receptor signaling pathway, B cell receptor signaling pathway, natural killer cell mediated cytotoxicity and Toll like receptor signaling pathway. The results of tissue enrichment showed that the key gene expression sites were mainly in lung and epithelial cells, involving a variety of immune cells, such as T cells, B cells, lymphocytes, etc. Molecular docking showed that the compounds with good binding power to SARS-CoV-2-RBD-ACE2 complex in Qingfei Dayuan granules were mainly come from Bupleuri Radix, Codonopsis Radix, Anemarrhenae Rhizoma, and Glycyrrhizae Radix et Rhizoma. Saikosaponin, glycyrrhizic acid, anemarsaponin had good binding power with SARS-CoV-2-S-RBD-ACE2, which may be potential active components against SARS-CoV-2. Conclusion: Qingfei Dayuan Granules has the characteristics of multi-components, multi-targets and multi-pathway regulation. Saikosaponin, glycyrrhizic acid, and anemarsaponin may be the potential active components against SARS-CoV-2. The mechanisms of its treatment against COVID-19 may be related to the regulation of the co-expressed genes with ACE2, inhibition of inflammation and immune related signaling pathways, and the destruction of the complex structure of SARS-CoV-2-S-RBD-ACE2.

6.
Int J Infect Dis ; 95: 436-440, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-155290

ABSTRACT

BACKGROUND: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. METHODS: Between January 2018 and March 2020, 1,027 NCPP and 1,140 IP were recruited from Tongji hospital. Routine blood examination, biochemical indicators and coagulation function analysis were simultaneously performed in all participants. RESULTS: There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56±16 years) was higher than IP (47±17 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant differences, some laboratory tests showed an obvious change in NCPP. It was observed that NCPP had significantly decreased white blood cells, alkaline phosphatase and d-dimer compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with IP. The diagnostic model based on a combination of 18 routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777-0.814), with a sensitivity of 46.93% and specificity of 90.09% when using a cut-off value of 0.598. CONCLUSIONS: Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on a combination of routine laboratory results provided an adjunct approach in the differential diagnosis between NCPP and IP.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Influenza, Human/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Diagnosis, Differential , Female , Humans , Leukocyte Count , Male , Middle Aged , Pandemics , SARS-CoV-2
7.
JCI Insight ; 5(10)2020 05 21.
Article in English | MEDLINE | ID: covidwho-118074

ABSTRACT

BACKGROUNDThe coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown.METHODSThe routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission.RESULTSA total of 65 SARS-CoV-2-positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ-producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ-producing CD4+ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients.CONCLUSIONThe number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.FUNDINGThis work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Betacoronavirus , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cytokines/metabolism , Diagnostic Tests, Routine , Female , Humans , Immunity , Lymphocyte Count , Male , Middle Aged , Pandemics , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology
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