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1.
Nature ; 599(7884): 283-289, 2021 11.
Article in English | MEDLINE | ID: covidwho-1404888

ABSTRACT

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.


Subject(s)
COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Cellular Senescence/drug effects , Molecular Targeted Therapy , SARS-CoV-2/pathogenicity , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Animals , COVID-19/complications , Cell Line , Cricetinae , Dasatinib/pharmacology , Dasatinib/therapeutic use , Disease Models, Animal , Female , Humans , Male , Mice , Quercetin/pharmacology , Quercetin/therapeutic use , SARS-CoV-2/drug effects , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thrombosis/complications , Thrombosis/immunology , Thrombosis/metabolism
2.
J Clin Lab Anal ; 35(8): e23871, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1361198

ABSTRACT

BACKGROUND: To verify the differential expression of miR-30c and miR-142-3p between tuberculosis patients and healthy controls and to investigate the performance of microRNA (miRNA) and subsequently models for the diagnosis of tuberculosis (TB). METHODS: We followed up 460 subjects suspected of TB, and finally enrolled 132 patients, including 60 TB patients, 24 non-TB disease controls (TB-DCs), and 48 healthy controls (HCs). The differential expression of miR-30c and miR-142-3p in serum samples of the TB patients, TB-DCs, and HCs were identified by reverse transcription-quantitative real-time PCR. Diagnostic models were developed by analyzing the characteristics of miRNA and electronic health records (EHRs). These models evaluated by the area under the curves (AUC) and calibration curves were presented as nomograms. RESULTS: There were differential expression of miR-30c and miR-142-3p between TB patients and HCs (p < 0.05). Individual miRNA has a limited diagnostic value for TB. However, diagnostic performance has been both significantly improved when we integrated miR-142-3p and ordinary EHRs to develop two models for the diagnosis of tuberculosis. The AUC of the model for distinguishing tuberculosis patients from healthy controls has increased from 0.75 (95% CI: 0.66-0.84) to 0.96 (95% CI: 0.92-0.99) and the model for distinguishing tuberculosis patients from non-TB disease controls has increased from 0.67 (95% CI: 0.55-0.79) to 0.94 (95% CI: 0.89-0.99). CONCLUSIONS: Integrating serum miR-142-3p and EHRs is a good strategy for improving TB diagnosis.

4.
Glob Health Res Policy ; 6(1): 18, 2021 05 28.
Article in English | MEDLINE | ID: covidwho-1247610

ABSTRACT

BACKGROUND: To put COVID-19 patients into hospital timely, the clinical diagnosis had been implemented in Wuhan in the early epidemic. Here we compared the epidemiological characteristics of laboratory-confirmed and clinically diagnosed cases with COVID-19 in Wuhan. METHODS: Demographics, case severity and outcomes of 29,886 confirmed cases and 21,960 clinically diagnosed cases reported between December 2019 and February 24, 2020, were compared. The risk factors were estimated, and the effective reproduction number (Rt) of SARS-CoV-2 was also calculated. RESULTS: The age and occupation distribution of confirmed cases and clinically diagnosed cases were consistent, and their sex ratio were 1.0 and 0.9, respectively. The epidemic curve of clinical diagnosis cases was similar to that of confirmed cases, and the city centers had more cumulative cases and higher incidence density than suburbs in both of two groups. The proportion of severe and critical cases (21.5 % vs. 14.0 %, P < 0.0001) and case fatality rates (5.2 % vs. 1.2 %, P < 0.0001) of confirmed cases were all higher than those of clinically diagnosed cases. Risk factors for death we observed in both of two groups were older age, male, severe or critical cases. Rt showed the same trend in two groups, it dropped below 1.0 on February 6 among confirmed cases, and February 8 among clinically diagnosed cases. CONCLUSIONS: The demographic characteristics and spatiotemporal distributions of confirmed and clinically diagnosed cases are roughly similar, but the disease severity and clinical outcome of clinically diagnosed cases are better than those of confirmed cases. In cases when detection kits are insufficient during the early epidemic, the implementation of clinical diagnosis is necessary and effective.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Basic Reproduction Number , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Epidemics , Female , Humans , Infant , Male , Middle Aged , Mortality , Retrospective Studies , Risk Factors , Young Adult
6.
J Infect Chemother ; 27(6): 876-881, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1091770

ABSTRACT

INTRODUCTION: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. METHODS: A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. RESULTS: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. CONCLUSIONS: In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.


Subject(s)
COVID-19/drug therapy , Ribavirin , Aged , China , Female , Humans , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Treatment Outcome
8.
Int J Clin Pract ; 75(8): e14031, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1039826

ABSTRACT

OBJECTIVE: The ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Excluded typical manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients also have abnormal D-dimer concentration in the serum, but the results are controversial. METHOD: A meta-analysis first aims to explored the connection between D-dimer concentration and COVID-19 patients. RESULTS: Our results found a significant relationship between D-dimer and COVID-19, with a pooled OR of 1.90 (95% CI: 1.32-2.48; P < .001). The pooled data were calculated with the REM as a high heterogeneity within the studies. The sensitivity analysis results showed that the WMD ranged from 1.69 (95% CI: 1.15 to 2.23) to 2.06 (95% CI: 1.51 to 2.62) and there was no publication bias. CONCLUSIONS: Our meta-analysis showed that the severity of patients with COVID-19 significance related to D-dimer concentrations. Meanwhile, the severe COVID-19 patients tend to have a higher concentration of D-dimer when compared with non-severe patients. REVIEW CRITERIA: We used MASH word and searched the online database and followed the inclusion and exclusion standard. The detailed information can be found in the text. MESSAGE FOR THE CLINIC: Our meta-analysis showed that the severity of patients with COVID-19 significance related to D-dimer concentrations. This may be helpful for the clinic COVID-19 patients.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products , Humans , Pandemics , SARS-CoV-2
9.
Glob Health Res Policy ; 5(1): 54, 2020 12 21.
Article in English | MEDLINE | ID: covidwho-992590

ABSTRACT

OBJECTIVES: To analyze the epidemiological characteristics of COVID-19 related deaths in Wuhan, China and comprehend the changing trends of this epidemic along with analyzing the prevention and control measures in Wuhan. METHODS: Through the China's Infectious Disease Information System, we collected information about COVID-19 associated deaths from December 15, 2019 to February 24, 2020 in Wuhan. We analyzed the patient's demographic characteristics, drew epidemiological curve and made geographic distribution maps of the death toll in each district over time, etc. ArcGIS was used to plot the numbers of daily deaths on maps. Statistical analyses were performed using SPSS and @Risk software. RESULTS: As of February 24, 2020, a total of 1833 deaths were included. Among the deaths with COVID-19, mild type accounted for the most (37.2%), followed by severe type (30.1%). The median age was 70.0 (inter quartile range: 63.0-79.0) years. Most of the deaths were distributed in 50-89 age group, whereas no deaths occurred in 0-9 age group. Additionally, the male to female ratio was 1.95:1. A total of 65.7% of the deaths in Wuhan combined with underlying diseases, and was more pronounced among males. Most of the underlying diseases included hypertension, diabetes and cardiovascular diseases. The peak of daily deaths appeared on February 14 and then declined. The median interval from symptom onset to diagnosis was 10.0 (6.0-14.0) days; the interval from onset to diagnosis gradually shortened. The median intervals from diagnosis to death and symptom onset to deaths were 6.0 (2.0-11.0), 17.0 (12.0-22.0) days, respectively. Most of the disease was centralized in central urban area with highest death rate in Jianghan District. CONCLUSION: COVID-19 poses a greater threat to the elderly people and men with more devastating effects, particularly in the presence of underlying diseases. The geographical distributions show that the epidemic in the central area of Wuhan is more serious than that in the surrounding areas. Analysis of deaths as of February 24 indicates that a tremendous improvement of COVID-19 epidemic in Wuhan has achieved by effective control measures taken by Wuhan Government.


Subject(s)
COVID-19/mortality , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Aged , Aged, 80 and over , China/epidemiology , Female , Fever/epidemiology , Humans , Male , Middle Aged
10.
Braz. j. infect. dis ; 24(2):178-179, 2020.
Article in English | LILACS (Americas), Grey literature | ID: grc-743029
11.
Bull World Health Organ ; 98(12): 830-841D, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-964002

ABSTRACT

Objective: To design models of the spread of coronavirus disease-2019 (COVID-19) in Wuhan and the effect of Fangcang shelter hospitals (rapidly-built temporary hospitals) on the control of the epidemic. Methods: We used data on daily reported confirmed cases of COVID-19, recovered cases and deaths from the official website of the Wuhan Municipal Health Commission to build compartmental models for three phases of the COVID-19 epidemic. We incorporated the hospital-bed capacity of both designated and Fangcang shelter hospitals. We used the models to assess the success of the strategy adopted in Wuhan to control the COVID-19 epidemic. Findings: Based on the 13 348 Fangcang shelter hospitals beds used in practice, our models show that if the Fangcang shelter hospitals had been opened on 6 February (a day after their actual opening), the total number of COVID-19 cases would have reached 7 413 798 (instead of 50 844) with 1 396 017 deaths (instead of 5003), and the epidemic would have lasted for 179 days (instead of 71). Conclusion: While the designated hospitals saved lives of patients with severe COVID-19, it was the increased hospital-bed capacity of the large number of Fangcang shelter hospitals that helped slow and eventually stop the COVID-19 epidemic in Wuhan. Given the current global pandemic of COVID-19, our study suggests that increasing hospital-bed capacity, especially through temporary hospitals such as Fangcang shelter hospitals, to isolate groups of people with mild symptoms within an affected region could help curb and eventually stop COVID-19 outbreaks in communities where effective household isolation is not possible.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Hospital Bed Capacity/statistics & numerical data , Mobile Health Units/organization & administration , China/epidemiology , Humans , Markov Chains , Models, Statistical , Pandemics , SARS-CoV-2
12.
Nano Today ; 36: 101037, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-939172

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic represents a severe global health threat. Selenium (Se), as one of the essential trace elements in human body, is well known for its antioxidant and immunity-boosting capabilities that induce a strong antiviral effect. In response to the global pandemic, we highlight here the current status of Se in combating different viruses, as well as the potential application of nano-selenium (nanoSe) in combating COVID-19.

13.
Int J Epidemiol ; 49(6): 1940-1950, 2021 01 23.
Article in English | MEDLINE | ID: covidwho-910372

ABSTRACT

BACKGROUND: The new coronavirus (COVID-19) rapidly resulted in a pandemic. We report the characteristics of patients with severe or critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan city, China, and the risk factors related to infection severity and death. METHODS: We extracted the demographic and clinical data of 7283 patients with severe COVID-19 infection from designated Wuhan hospitals as of 25 February 2020. Factors associated with COVID-19 critical illness and mortality were analysed using logistic- and Cox-regression analyses. RESULTS: We studied 6269 patients with severe COVID-19 illness and 1014 critically ill patients. The median (IQR) age was 64 (53-71) years; 51.2% were male, 38.9% were retirees and 7.4% had self-reported histories of chronic disease. Up to the end of the study, 1180 patients (16.2%) recovered and were discharged, 649 (8.9%) died and the remainder were still receiving treatment. The number of daily confirmed critical cases peaked between 23 January and 1 February 2020. Patients with advanced age [odds ratio (OR), 1.03; 95% confidence intervals (CIs), 1.03-1.04], male sex (OR, 1.57; 95% CI, 1.33-1.86) and pre-existing diabetes (OR, 2.11), hypertension (OR, 2.72), cardiovascular disease (OR, 2.15) or respiratory disease (OR, 3.50) were more likely to be critically ill. Compared with those who recovered and were discharged, patients who died were older [hazard ratio (HR), 1.04; 95% CI, 1.03-1.05], more likely to be male (HR, 1.74; 95% CI, 1.44-2.11) and more likely to have hypertension (HR, 5.58), cardiovascular disease (HR, 1.83) or diabetes (HR, 1.67). CONCLUSION: Advanced age, male sex and a history of chronic disease were associated with COVID-19 critical illness and death. Identifying these risk factors could help in the clinical monitoring of susceptible populations.


Subject(s)
COVID-19/mortality , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Hypertension/epidemiology , Respiratory Tract Diseases/epidemiology , SARS-CoV-2/isolation & purification , Aged , China/epidemiology , Comorbidity , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Retrospective Studies , Treatment Outcome
14.
Biomed Environ Sci ; 33(8): 614-619, 2020 Aug 20.
Article in English | MEDLINE | ID: covidwho-771380

ABSTRACT

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever (< 37.3 °C), but shorter cough and fever duration, lower body temperature, and lower rates of cough, fever, high fever (> 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Influenza, Human/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , COVID-19 , Case-Control Studies , Child , Coronavirus Infections/blood , Coronavirus Infections/immunology , Female , Humans , Influenza, Human/blood , Influenza, Human/immunology , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , SARS-CoV-2
16.
Chin J Acad Radiol ; : 1-6, 2020 May 11.
Article in English | MEDLINE | ID: covidwho-232587

ABSTRACT

Purpose: To explore lung involvement in patients with coronavirus disease-19 (COVID-19) using quantitative computed tomography (QCT). Methods: A total of 52 patients with COVID-19 who were admitted to three hospitals in China from January 23, 2020 to February 1, 2020 were retrospectively analyzed using QCT. The accuracy of QCT segmentation was assessed. The relationship between the time from symptom onset to initial CT and QCT parameters acquired on the initial CT were explored. Results: First, the ability of QCT to detect and segment lesions was investigated and it was unveiled that results of segmentation of the majority of cases (42/52) were satisfactory and for 8 out of 52 patients, the images depicted lesions with miss-segmentation; besides, 2 out of 52 cases had negative finding on chest CT achieved by both radiologists and QCT. QCT-related parameters showed to have a relationship with the time from symptom onset to initial CT. In the early-stage (0-3 days), the percentage of lung involvement was 4%, with a mean density of - 462 ± 99 HU. The peak density of lesions appeared at the range of - 500 to - 700 HU on density histogram. In the intermediate-stage (4-6 days), the mean percentage of lung involvement noticeably increased compared with that in early stage (7%, p < 0.05). In late stage (7-14 days), the percentage of lung involvement decreased to 5%. The mean density of lesions was the highest (- 430 ± 80), and heterogeneity density distribution showed a dual-peak on density histogram. Conclusion: COVID-19 can be promptly detected by QCT. In addition, the QCT-related parameters can highly facilitate assessment of pulmonary involvement.

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