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1.
Aging Dis ; 11(2): 216-228, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1102674

ABSTRACT

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

2.
Eur J Radiol ; 137: 109602, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1084604

ABSTRACT

PURPOSE: Differentiating COVID-19 from other acute infectious pneumonias rapidly is challenging at present. This study aims to improve the diagnosis of COVID-19 using computed tomography (CT). METHOD: COVID-19 was confirmed mainly by virus nucleic acid testing and epidemiological history according to WHO interim guidance, while other infectious pneumonias were diagnosed by antigen testing. The texture features were extracted from CT images by two radiologists with 5 years of work experience using modified wavelet transform and matrix computation analyses. The random forest (RF) classifier was applied to identify COVID-19 patients and images. RESULTS: We retrospectively analysed the data of 95 individuals (291 images) with COVID-19 and 96 individuals (279 images) with other acute infectious pneumonias, including 50 individuals (160 images) with influenza A/B. In total, 6 texture features showed a positive association with COVID-19, while 4 features were negatively associated. The mean AUROC, accuracy, sensitivity, and specificity values of the 5-fold test sets were 0.800, 0.722, 0.770, and 0.680 for image classification and 0.858, 0.826, 0.809, and 0.842 for individual classification, respectively. The feature 'Correlation' contributed most both at the image level and individual level, even compared with the clinical factors. In addition, the texture features could discriminate COVID-19 from influenza A/B, with an AUROC of 0.883 for images and 0.957 for individuals. CONCLUSIONS: The developed texture feature-based RF classifier could assist in the diagnosis of COVID-19, which could be a rapid screening tool in the era of pandemic.


Subject(s)
COVID-19 , Humans , Machine Learning , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
4.
Front Immunol ; 11: 585647, 2020.
Article in English | MEDLINE | ID: covidwho-874483

ABSTRACT

Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-γ (IFN-γ) levels were twofold lower than those without fibrosis (p > 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-γ levels with an estimate of 0.43 (p = 0.02). Per the 1-SD increase of basal IFN-γ level in circulation, the fibrosis volume decreased by 0.070% (p = 0.04) at the discharge of participants. The basal circulating IFN-γ levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-γ is a risk factor of lung fibrosis in COVID-19.


Subject(s)
Coronavirus Infections/complications , Interferon-gamma/blood , Pneumonia, Viral/complications , Pulmonary Fibrosis/etiology , Aged , Artificial Intelligence , Biomarkers/blood , COVID-19 , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/immunology , Cross-Sectional Studies , Female , Humans , Inflammation/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/immunology , Pulmonary Fibrosis/blood , Pulmonary Fibrosis/diagnostic imaging , Risk Factors , Tomography, X-Ray Computed
5.
Signal Transduct Target Ther ; 5(1): 240, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-872677

ABSTRACT

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Lung Injury/genetics , Pneumonia, Viral/genetics , Proteome/genetics , Proteomics/methods , Severe Acute Respiratory Syndrome/genetics , Aged , Autopsy , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/genetics , Cytokines/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Lung Injury/metabolism , Lung Injury/pathology , Lung Injury/virology , Male , Metabolic Networks and Pathways , Molecular Sequence Annotation , NF-kappa B/genetics , NF-kappa B/metabolism , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Proteome/metabolism , SARS-CoV-2 , Severe Acute Respiratory Syndrome/metabolism , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Signal Transduction
6.
Intern Emerg Med ; 16(4): 875-882, 2021 06.
Article in English | MEDLINE | ID: covidwho-846869

ABSTRACT

A novel human coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic of coronavirus disease 2019 (COVID-19). In this study, we aimed to explore the clinical characteristics and outcomes in older patients with COVID-19. Ninety-one patients with SARS-CoV-2 infection were included in the study, 27 of which (29.67%) were elderly. The median age of these 27 patients was 74.9 years (interquartile range 68-82; range 65-94 years), and 15 (55.56%) were female. Elderly with COVID-19 in Beijing (China) were more likely to have underlying comorbidities and more frequently tended to have critical illness and suffer from more complications. The main treatments of the elderly consisted of symptomatic and respiratory support. The most frequent complications in the elderly were pleural effusion [10, (37.04%)], secondary infection [7, (25.93%)], and kidney damage [7, (25.93%)]. Six (22.22%) of the 27 elderly patients received invasive ventilation (three of them switched to extracorporeal membrane oxygenation). As of March 7, 20 (74.07%) of the 27 elderly patients were discharged, two (7.41%) were still hospitalized, and five died; the mortality in the elderly was 18.52%. Age was associated with the mortality in patients with COVID-19 (OR 0.82; 95% CI 0.70-0.97; P = 0.019). Therefore, more attention should be paid to the treatment of comorbidities and complications in elderly patients.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Age Factors , Aged , Aged, 80 and over , COVID-19/therapy , China , Critical Care , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate
7.
Chinese Journal of Nosocomiology ; 30(10):1452-1457, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-826354

ABSTRACT

OBJECTIVE: To rapidly establish a prevention and control system in response to the epidemic so as to reduce the risk of infection in medical staff during diagnosis and treatment of patients with confirmed COVID-19, other patients and their family members. METHODS: The strategies for prevention and control of nosocomial infection that were carried out during the treatment of the COVID-19 patients, including personnel management, material management, process management and execution supervision, were summarized and analyzed. RESULTS: The working group on prevention and control of the epidemic ran efficiently, the classification of the personnel in medical institutions, classification and division management, scientific assessment of usage amount of protective equipment, reasonable allocation and surveillance of epidemiological history and symptoms covered all the patients and working staff of the entire hospital, the construction was combined with the working process, the control line was effectively implemented, and the status of implementation of the measures was rigidly checked out. CONCLUSION: The scientific implementation of the prevention and control strategies maintains orderly diagnosis and treatment of the patients with COVID-19 and effectively prevent hospital-acquired COVID-19.

9.
Front Cell Infect Microbiol ; 10: 318, 2020.
Article in English | MEDLINE | ID: covidwho-615471

ABSTRACT

Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Severity of Illness Index , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , China , Comorbidity , Disease Progression , Female , Glomerular Filtration Rate/physiology , Humans , Leukocyte Count , Male , Middle Aged , Myoglobin/analysis , Neutrophil Infiltration/immunology , Neutrophils/immunology , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2
10.
J Infect Dis ; 222(1): 34-37, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-599711

ABSTRACT

A major unanswered question in the current global coronavirus disease 2019 (COVID-19) outbreak is why severe disease develops in a small minority of infected individuals. In the current article, we report that homozygosity for the C allele of rs12252 in the interferon-induced transmembrane protein 3 (IFITM3) gene is associated with more severe disease in an age-dependent manner. This supports a role for IFITM3 in disease pathogenesis and the opportunity for early targeted intervention in at-risk individuals.


Subject(s)
Alleles , Betacoronavirus/genetics , Coronavirus Infections/genetics , Membrane Proteins/genetics , Pneumonia, Viral/genetics , Polymorphism, Single Nucleotide , RNA-Binding Proteins/genetics , Severity of Illness Index , Adult , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Coronavirus Infections/virology , Female , Genotype , High-Throughput Nucleotide Sequencing , Homozygote , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , SARS-CoV-2
11.
JCI Insight ; 5(13)2020 07 09.
Article in English | MEDLINE | ID: covidwho-541270

ABSTRACT

BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.


Subject(s)
Chemokine CCL5/immunology , Coronavirus Infections/immunology , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin-10/immunology , Pneumonia, Viral/immunology , Adult , Aged , Betacoronavirus , COVID-19 , Case-Control Studies , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Female , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Hospitalization , Humans , Immunoassay , Interferon-gamma/immunology , Interleukin-6/immunology , Longitudinal Studies , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , Tumor Necrosis Factor-alpha/immunology
12.
Infect Dis (Lond) ; 52(7): 498-505, 2020 07.
Article in English | MEDLINE | ID: covidwho-186351

ABSTRACT

Background: To investigate the risk factors related to aggravation and clinical outcomes in coronavirus disease 2019 (COVID-19) patients.Methods: We performed a retrospective study on the risk factors for disease progression of cases with COVID-19. Based on the clinical types, the patients were divided into a progression group and an improvement group. Multivariable logistic regression and ROC curve analysis were performed to explore the risk factors for disease progression.Results: A total of 101 patients were included in this study; diseases progression occurred in 17 patients, 84 patients improved, 6 were transferred to intensive care unit (ICU), and 5 died. The mean time to obtain negative nucleic acid results was 12.5 ± 5.0 days. Multivariate logistic analysis indicated that age (OR, 0.104; p = .002), C-reactive protein (CRP) (OR, 0.093; p < .001) and lymphocyte count (OR, 3.397; p = .022) were risk factors for disease progression. ROC curve analysis revealed that the AUC of age, CRP and lymphocyte count for disease progression were 0.873, 0.911 and 0.817, respectively.Conclusions: Older age increased CRP and decreased lymphocyte count resulted in potential risk factors for COVID-19 progression. This may be helpful in identifying patients whose condition worsens at an early stage.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Adult , Aged , Beijing/epidemiology , C-Reactive Protein/metabolism , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/therapy , Coronavirus Infections/virology , Disease Progression , Female , Hospitalization , Humans , Intensive Care Units , Logistic Models , Lymphocyte Count , Male , Middle Aged , Multivariate Analysis , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
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