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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325094

ABSTRACT

Background: Coronavirus Disease-2019 (COVID-19) has caused considerable morbidity and mortality. Hence, there is an urgency to find effective treatment. Tocilizumab, an inhibitor of IL-6, has been widely proposed as a treatment of severely ill patients without robust evidence supporting its use. Methods: In this multicentre, retrospective, cohort study, we included 5,235 adult patients who were admitted to 3 hospitals in Wuhan, China with confirmed COVID-19 from January 20 to March 18, 2020 . 65 patients in tocilizumab group and 130 patients in non-tocilizumab group were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities. Detailed demographic data, comorbidities, radiological and laboratory parameters, complications and treatments were compared between tocilizumab group and non-tocilizumab group. Furthermore, univariable and multivariable Logistic and Cox regression models were used to explore the risk of complications and in-hospital death associated with tocilizumab. Findings: During the follow-up, patients in non-tocilizumab group were more likely to develop into death (42 [32·31%] vs 14 [21·54%]). After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus the non-tocilizumab group (HR=0·47;95% CI=0·25-0·90;p=0·023). In the multivariable logistic regression model, use of tocilizumab was associated with a lower risk of ARDS (OR=0 · 23;95% CI=0·11-0·45;p<0·0001). Before treatment the patients had heightened inflammation and more dysregulated immune cells, which might aggravate disease progression. However, abnormally elevated IL-6, CRP, fibrinogen and APTT decreased in COVID-19 patients after treatment. And the counts of lymphocytes and immune cells subset in peripheral blood, which decreased in patients, returned to normal after treatment. No obvious complications were observed. Interpretation: Tocilizumab may be of value in improving outcomes in severe patients of COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome (CRS). Our preliminary data could inform bedside decisions until more data from randomized, controlled clinical trials becomes available.Funding Statement: SARS-CoV-2 Pneumonia Emergency Technology Public Relations Project of Tongji Medical College, Huazhong University of Science and Technology (No. 2020kfyXGYJ043) and National Key Research and Development Plan for the Emergency Management of Novel Coronavi rus Pneumonia, China (No. 2020YFC0845100).Declaration of Interests: The authors report no conflicts of interest.Ethics Approval Statement: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-C20200108) and granted a waiver of informed consent from study participants.

3.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1066781

ABSTRACT

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.


Subject(s)
COVID-19/metabolism , DNA-Binding Proteins/metabolism , Macrophages/metabolism , Pulmonary Fibrosis/metabolism , Animals , Bleomycin/pharmacology , Carcinoma, Non-Small-Cell Lung/metabolism , Fibrosis , Gene Expression Profiling , Gene Expression Regulation , Humans , Liposomes/chemistry , Lung Diseases, Interstitial/metabolism , Lung Neoplasms/metabolism , Macrophages/virology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Pulmonary Fibrosis/virology , RNA, Small Interfering/metabolism , Scleroderma, Systemic/metabolism , Signal Transduction , Transforming Growth Factor beta1/metabolism
5.
J Immunol ; 206(3): 599-606, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-969665

ABSTRACT

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/drug therapy , Drug Repositioning , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/drug therapy , Aged , COVID-19/immunology , Cohort Studies , Cytokine Release Syndrome/immunology , Female , Humans , Interleukin-6/immunology , Male , Middle Aged , Respiratory Distress Syndrome/immunology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
6.
J Med Virol ; 92(11): 2870-2873, 2020 11.
Article in English | MEDLINE | ID: covidwho-935144

ABSTRACT

In this study, we performed a single-centered study of 307 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. It was found that co-infection of SARS-CoV-2 and influenza virus was common during COVID-19 outbreak. And patients coinfected with SARS-CoV-2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID-19 outbreak.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Coinfection/virology , Disease Outbreaks/statistics & numerical data , Influenza, Human/epidemiology , Adult , Aged , China/epidemiology , Female , Humans , Influenza A virus/pathogenicity , Influenza B virus/pathogenicity , Male , Middle Aged , Retrospective Studies
7.
J Asthma ; 59(2): 230-238, 2022 02.
Article in English | MEDLINE | ID: covidwho-922319

ABSTRACT

OBJECTIVE: Although it is reported that patients with coronavirus disease 2019 (COVID-19) disease who have comorbidities are at higher risk to suffer adverse clinical outcomes, there are inadequate evidence to clarify the association between COVID-19 and asthma. On this ground, this study aims to systematically analyze the clinical characteristics of COVID-19 patients with asthma. METHODS: In this single-center, retrospective and observational cohort study, 21 COVID-19 patients with asthma and 100 non-asthma COVID-19 patients were statistically matched by propensity score based on age, sex and comorbidities. Meanwhile, a collection and comparison concerning demographic indicators, clinical and laboratory examinations, treatments and outcomes were conducted between two groups to specify their differences. RESULTS: Statistically, the COVID-19 patients with asthma had a higher proportion of ICU admission (14.3% [3/21] vs. 2.1% [2/96] p = 0.040) than those who do not have. On top this, a higher level of inflammatory responses, such as interleukin 6, interleukin 8, procalcitonin, leukocytes, neutrophils and CD4+ T cells was presented in asthma patients. Moreover, the increase of organ damage indices like D-dimer, lactate dehydrogenase and high-sensitivity cardiac troponin I, were more pronounced in COVID-19 patients with asthma. CONCLUSIONS: Exacerbated inflammatory responses and multiple organ damages were triggered in COVID-19 patients with asthma, which highlights more intensive surveillance and supportive treatment.


Subject(s)
Asthma/epidemiology , COVID-19/epidemiology , COVID-19/physiopathology , Adult , Age Factors , Aged , China/epidemiology , Comorbidity , Female , Humans , Inflammation Mediators/metabolism , Intensive Care Units , Male , Middle Aged , Organ Dysfunction Scores , Retrospective Studies , SARS-CoV-2 , Sex Factors
8.
ERJ Open Res ; 6(2)2020 Apr.
Article in English | MEDLINE | ID: covidwho-853162

ABSTRACT

In response to the early outbreak of SARS-CoV-2, online fever clinics were set up. Then, an online face-to-face consultation was developed to solve the extreme difficulty of getting medical services to patients with chronic diseases. http://bit.ly/3cPppai.

9.
J Med Virol ; 92(7): 807-813, 2020 07.
Article in English | MEDLINE | ID: covidwho-823738

ABSTRACT

In December 2019, an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection occurred in Wuhan, and rapidly spread to worldwide, which has attracted many people's concerns about the patients. However, studies on the infection status of medical personnel is still lacking. A total of 54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between 7 January and 11 February 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. From 7 January to 11 February 2020, 54 medical staff of Tongji Hospital were hospitalized due to coronavirus disease 2019 (COVID-19). Most of them were from other clinical departments (72.2%) rather than emergency department (3.7%) or medical technology departments (18.5%). Among the 54 patients with COVID-19, the distribution of age had a significant difference between non-severe type and severe/critical cases (median age: 47 years vs 38 years; P = .0015). However, there was no statistical difference in terms of gender distribution and the first symptoms between theses two groups. Furthermore, we observed that the lesion regions in SARS-Cov-2 infected lungs with severe-/critical-type of medical staff were more likely to exhibit lesions in the right upper lobe (31.7% vs 0%; P = .028) and right lung (61% vs 18.2%; P = .012). Based on our findings with medical staff infection data, we suggest training for all hospital staff to prevent infection and preparation of sufficient protection and disinfection materials.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Infectious Disease Transmission, Patient-to-Professional/classification , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Female , Hospital Departments/classification , Humans , Immunoglobulins/therapeutic use , Interferons/therapeutic use , Male , Medical Staff, Hospital , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
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