Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Front Cell Infect Microbiol ; 12: 880915, 2022.
Article in English | MEDLINE | ID: covidwho-1847156

ABSTRACT

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection.


Subject(s)
COVID-19 , Liver Failure, Acute , Murine hepatitis virus , Animals , Complement Activation , Liver Failure, Acute/pathology , Mice , Mice, Inbred C57BL
2.
Signal Transduct Target Ther ; 7(1): 139, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815514

ABSTRACT

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/genetics , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Cryoelectron Microscopy , Epitopes , Humans , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Envelope Proteins
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324975

ABSTRACT

Background: No therapeutics have demonstrated specific efficacy for patients with COVID-19. Methods We retrospectively evaluated 351 patients with COVID-19 admitted to the Third People's Hospital of Yichang from 9 January to 25 March, 2020.Univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were employed to identify risk factors associated with progression, which were then incorporated into the nomogram. Survival of patients between high-risk and low-risk groups was compared by kaplan-Meier analysis. Moreover, we assessed the effects of existing common drugs on survival of patients with high-risk. Results Based on the LASSO, four variables (white blood cell, C-reactive protein, whether lymphocyte ≥ 0.8 × 10 9 /L, and whether lactate dehydrogenase ≥ 400 U/L) were selected for construction of the nomogram. Patients in the total cohort were stratified into low-risk group (total point < 160) and high-risk group (total point ≥ 160). Kaplan-Meier analysis demonstrated that there was significant difference in survival of patients between high-risk and low-risk groups (8-week survival rate: 71.41% vs 100%, P < 0.0001). Among the common drugs, we found that patients with high-risk received oseltamivir, lopinavir/ritonavir or Reduning injection exhibited better survival. The combination of these three drugs showed the effect of improving survival, although single drug may have no effect in different grouping analysis. Conclusions The combination of oseltamivir, lopinavir/ritonavir and Reduning injection may improve survival of COVID-19 patients with high-risk identified by our simple-to-use nomogram.

4.
Respir Physiol Neurobiol ; 297: 103813, 2022 03.
Article in English | MEDLINE | ID: covidwho-1521498

ABSTRACT

This study was aimed to explore the precise dose of corticosteroid therapy in critical COVID-19. A total of forty-five critical COVID-19 patients were enrolled. The process of critical COVID-19 was divided into alveolitis and fibrosis stages. Most nonsurvivors died in fibrosis phase. Nonsurvivors had more dyspnea symptoms, fewer days of hospitalization, shorter duration of alveolitis and fibrosis. High-dose daily corticosteroid therapy (≥150 mg/d) was associated with shorter survival time and lower lymphocyte count in fibrosis phase. Moreover, a high cumulative dose (≥604 mg) was tied to longer duration of virus shedding, lower oxygenation index (OI), higher incidence of tracheal intubation, fewer lymphocytes and higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In alveolitis phase, the low-to-moderate-dose daily corticosteroid therapy and a small cumulative dose reduced lymphocytes. In conclusion, low-to-moderate dose corticosteroids may be beneficial in the fibrosis phase. High-dose corticosteroid therapy in the fibrosis phase aggravates the severity of critical COVID-19.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/administration & dosage , Lung/diagnostic imaging , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Aged , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/physiopathology , Critical Illness , Female , Fibrosis , Glucocorticoids/therapeutic use , Humans , L-Lactate Dehydrogenase/metabolism , Lung/pathology , Lung/physiopathology , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Prednisolone/administration & dosage , Prednisolone/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Survival Rate , Tomography, X-Ray Computed , Virus Shedding
5.
Educational Measurement: Issues & Practice ; : 1, 2021.
Article in English | Academic Search Complete | ID: covidwho-1226669

ABSTRACT

With the emergence of COVID‐19 worldwide, interest in blended learning in higher education is rapidly increasing. Despite the fact that the unipolar view that satisfaction and dissatisfaction are measured separately has been emphasized in higher education, fewer efforts have been made in a blended learning context. Therefore, this study attempts to document the unipolar view of satisfaction and dissatisfaction in a blended learning context by adopting the Kano model. More specifically, the objectives of this study is to (1) conceptualize online and offline service dimensions in blended learning, (2) examine the asymmetric effect between satisfaction and dissatisfaction, and (3) apply those results to the Kano model. The following results are reported: (1) system quality and assurance are symmetric, functioning as a satisfier;and (2) information quality, responsiveness, and tangibility are asymmetric, functioning as a delighter. Theoretical and practical implications are addressed. [ABSTRACT FROM AUTHOR] Copyright of Educational Measurement: Issues & Practice is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

6.
BMC Infect Dis ; 21(1): 356, 2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1190061

ABSTRACT

BACKGROUND: COVID-19 pandemic has forced physicians to quickly determine the patient's condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients. METHODS: A total of 351 COVID-19 patients admitted to the Third People's Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point. RESULTS: The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 109/L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91-0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P < 0.0001). CONCLUSION: A simple-to-use nomogram with excellent performance in predicting deterioration risk and survival of COVID-19 patients was developed and validated. However, it is necessary to verify this nomogram using a large-scale multicenter study.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Nomograms , Adult , Aged , C-Reactive Protein/analysis , China , Female , Hospitalization , Humans , L-Lactate Dehydrogenase/blood , Leukocyte Count , Logistic Models , Male , Middle Aged , Pandemics , ROC Curve , Retrospective Studies , Risk Factors , Survival Rate
7.
J Multidiscip Healthc ; 14: 629-637, 2021.
Article in English | MEDLINE | ID: covidwho-1140594

ABSTRACT

PURPOSE: COVID-19 is a new infectious disease with global spread. The aim of the present study was to explore possible risk factors and evaluate prognosis in COVID-19 with liver injury. METHODS: A retrospective study was conducted on 356 COVID-19 patients in the Third People's Hospital of Yichang, Hubei, China. Clinical characteristics and laboratory tests between patients with and without liver injury were compared, while risk factors of COVID-19-related liver injury were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify risk factors of in-hospital death. RESULTS: Of the patients with liver injury, severe and critical types of COVID-19 comprised 12.43% and 14.69%, respectively, higher than in patients without liver injury (both P<0.05). CRP and male sex were independent risk factors for for patients with liver injury, while decreased lymphocyte count (HR 0.024, 95% CI 0.001-0.821) and elevated monocytes (HR 1.951, 95% CI 1.040-3.662) and CRP (HR 1.028, 95% CI 1.010-1.045) were independent risk factors of prognosis of death in COVID-19 patients with liver injury. CONCLUSION: Liver injury is a common complication in severe COVID-19 patients. Male sex and elevated CRP were independent risk factors in COVID-19 complicated by liver damage. Liver damage with increased CRP and monocyte count and decreased lymphocyte count may imply a poor prognosis.

8.
J Med Virol ; 92(10): 2152-2158, 2020 10.
Article in English | MEDLINE | ID: covidwho-260279

ABSTRACT

The coronavirus disease 2019 (COVID-19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID-19 are of little clinical significance. Lower albumin level is seen in severe COVID-19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID-19. This retrospective cohort study included adult patients with confirmed COVID-19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2-5). Approximately one-third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non-survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = -.149, P = .01) and neutrophil to lymphocyte ratio (r = -.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361-34.133), lymphopenia (OR, 13.130; 95% CI, 1.632-105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315-31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID-19. The potential therapeutic value of albumin infusion in COVID-19 should be further explored at the earliest.


Subject(s)
COVID-19/diagnosis , Hospitalization/statistics & numerical data , Hypoalbuminemia/complications , Adult , Age Factors , Aged , COVID-19/physiopathology , China , Comorbidity , Electronic Health Records , Female , Humans , Liver Diseases/blood , Liver Diseases/complications , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors
9.
Am J Transplant ; 20(7): 1879-1881, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-101378

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020. We describe here 2 cases of COVID-19 infection in a posttransplant setting. First one is a 59-year-old renal transplant recipient; the second is a 51-year-old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID-19 infection. After the diagnosis of COVID-19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID-19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.


Subject(s)
Bone Marrow Transplantation , Coronavirus Infections/complications , Kidney Failure, Chronic/complications , Kidney Transplantation , Leukemia, Myeloid, Acute/complications , Pneumonia, Viral/complications , Transplant Recipients , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/complications , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Cross Infection/complications , Fatal Outcome , Humans , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/surgery , Leukemia, Myeloid, Acute/therapy , Male , Methylprednisolone/administration & dosage , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Postoperative Complications , Prognosis , Respiration, Artificial , T-Lymphocytes/cytology
SELECTION OF CITATIONS
SEARCH DETAIL