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1.
Front Public Health ; 10: 833967, 2022.
Article in English | MEDLINE | ID: covidwho-1731872

ABSTRACT

Recent advances in the pathophysiologic understanding of coronavirus disease 2019 (COVID-19) suggests that cytokine release syndrome (CRS) has an association with the severity of disease, which is characterized by increased tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-2, IL-7, and IL-10. Hence, managing CRS has been recommended for rescuing severe COVID-19 patients. TNF-α, one of the pro-inflammatory cytokines commonly upregulated in acute lung injury, triggers CRS and facilitates SARS-CoV-2 interaction with angiotensin-converting enzyme 2 (ACE2). TNF-α inhibitors, therefore, may serve as an effective therapeutic strategy for attenuating disease progression in severe SARS-CoV-2 infection. Below, we review the possibilities and challenges of targeting the TNF-α pathway in COVID-19 treatment.


Subject(s)
COVID-19 , COVID-19/drug therapy , Cytokine Release Syndrome , Humans , SARS-CoV-2 , Tumor Necrosis Factor-alpha/metabolism
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315643

ABSTRACT

Background: The novel coronavirus disease (COVID-19) is leading to high morbidity and mortality. This study aimed to test whether blood urea nitrogen-to-creatinine ratios (BCR) is a predictor of poor prognosis in patients with COVID-19. Method: From 9,165 generally healthy subjects, we calculated ranges of “normal” BCR values. 416 COVID-19 patients were randomly assigned to training cohort and validation cohort contained 337, 79 patients, respectively. The prognostic ability of abnormal BCR range was assessed using a Logistic regression. Development a nomogram for predicting in-hospital mortality incorporated age, sex and BCR. The model discrimination was assessed using the calibration curves and concordance index in training and validation cohort. The predictive accuracy and clinical values of the nomogram was measured by decision curve analysis (DCA) and clinical impact curve analysis (CICA). Results: : Among 337 COVID-19 patients, 13.4% and 11.3% were classified into higher and lower than normal range group, respectively. The BCR was identified as an independent risks factor for death in COVID-19 patients (P<0.0001), with area under the curve (AUC) 0.768;95%CI: 0.717-0.819). Kaplan-Meier curves for all-cause mortality outcomes showed that patients with above normal range of BCR had worse prognosis (p<0.0001). Logistic regression analysis revealed that BCR above the normal range was independently associated with death in COVID-19 patients (Odds ratio 7.54;95%CI: 1.55-36.66;P=0.012). ROC curves showed that the nomogram had good discrimination in the training cohort (AUC 0.838;95%CI 0.795–0.880) and the validation cohort (AUC 0.929;95%CI 0.869-0.989). Using maximum Youden index, the cutoff values of 59.8 points, the sensitivity and specificity were 75.4% and 81%. The calibration curves showed good agreement between nomogram prediction and actual observation. DCA and CICA indicated the clinical usefulness of the prediction nomogram. Conclusion: BCR was a useful prognostic factor for COVID-19 patients. Development of an individualized prediction nomogram BCR-based, which can effectively predict the risk of mortality, and then, help clinicians to improve individual treatment, make clinical decisions timely and early.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311723

ABSTRACT

Background: Deep venous thrombosis (DVT) is a severe complication of the coronavirus disease 2019 (COVID-19). It may interfere with COVID-19 treatment and delay the recovery, but there is less data about the anticoagulant therapy and sex difference of VTE in patients with COVID-19. The purpose of this study is to study the prevalence, risk factors, anticoagulant therapy and sex difference of deep venous thrombosis (DVT) in patients with COVID-19. Methods: The enrolled 121 patients were confirmed positive for COVID-19. All suspected patients with a high Caprini index (≥4) or PADUA index (≥4) received color Doppler Ultrasound (US) to screen DVT in both lower extremities. Clinical characteristics of DVT-COVID-19 patients were analyzed. Multivariate logistic regression was performed to identify risk factors related to DVT in COVID-19 patients. The distribution of DVT locations, anticoagulation therapy with sex difference, and the outcomes were also analyzed. Results: DVT was found in 48% asymptomatic COVID-19 patients with increased PAUDA index or Caprini index by US scanning. Multivariate logistic regression determined that age, CRP and baseline D-dimer were risk factors among COVDI-19 patients. Although the most common DVT location was infrapopliteal (Class I and Class II), higher mortality in DVT-COVID-19 patients was confirmed. DVT-COVID-19 patients presented significant increases in the CRP, neutrophil count and D-dimer throughout the whole inpatient period compared to non-DVT-COVID-19 patients. Although anticoagulation therapy accelerated the recovery of lymphocytopenia condition in DVT patients, men DVT-COVID-19 patients showed higher CRP and neutrophil count vs. lymphocyte count (N/L) ratio but lower lymphocyte count compared to women DVT-COVID-19 patients. Conclusions: DVT is common in COVID-19 patients with high risk factors, especially for older age, higher CRP and baseline D-dimer populations. It is important to consider sex differences in the anticoagulant therapy among DVT-COVID-19 patients.

5.
J Med Virol ; 93(4): 1999-2009, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217364

ABSTRACT

This study aims to screen useful predictors of critical cases among coronavirus disease 2019 (COVID-19) patients and to develop a simple-to-use nomogram for clinical utility. A retrospective study was conducted that consisted of a primary cohort with 315 COVID-19 patients and two validation cohorts with 69 and 123 patients, respectively. Logistic regression analyses were used to identify the independent risks of progression to critical. An individualized prediction model was developed, and calibration, decision curve, and clinical impact curves were used to assess the performance of the model. External validations for the predictive nomogram were also provided. The variables of age, comorbid diseases, neutrophil-to-lymphocyte ratio, d-dimer, C-reactive protein, and platelet count were estimated to be independent predictors of progression to critical, which were incorporated to establish a model of the nomogram. It demonstrated good discrimination (with a C-index of 0.923) and calibration. Good discrimination (C-index, 0.882 and 0.906) and calibration were also noted on applying the nomogram in two validation cohorts. The clinical relevance of the nomogram was justified by the decision curve and clinical impact curve analysis. This study presents an individualized prediction nomogram incorporating six clinical characteristics, which can be conveniently applied to assess an individual's risk of progressing to critical COVID-19.


Subject(s)
COVID-19/epidemiology , Critical Illness , Nomograms , Adult , Aged , China , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment
6.
Risk Manag Healthc Policy ; 14: 117-128, 2021.
Article in English | MEDLINE | ID: covidwho-1038557

ABSTRACT

BACKGROUND: The novel coronavirus disease (COVID-19) is leading to high morbidity and mortality. This aim of this study was to test whether blood urea nitrogen-to-creatinine ratio (BCR) is a predictor for mortality in patients with COVID-19. METHODS: Ranges of "normal" BCR values were calculated from 9165 healthy subjects, and 337 and 79 COVID-19 patients were randomly assigned to the training cohort and the validation cohort, respectively. Prognostic factor of death incidence was selected by LASSO regression analyses. The prognostic ability of BCR range was assessed by logistic regression analysis. A nomogram for predicting in-hospital mortality based on BCR was developed. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. RESULTS: Among 337 COVID-19 patients, 13.4% and 11.3% were classified into higher and lower than normal range group, respectively. Kaplan-Meier curves for all-cause mortality showed that patients with higher BCR group had worse prognosis (P<0.0001). BCR above the normal range was independently associated with death in COVID-19 patients (OR: 7.54; 95%CI: 1.55-36.66; P=0.012). The nomogram had good discrimination in the training cohort (C-index 0.838; 0.795-0.880) and the validation cohort (C-index 0.929; 0.869-0.989), and good calibration. Using maximum Youden index, the cutoff values of 59.8 points, the sensitivity and specificity were 75.4% and 81%. Decision curve and clinical impact curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: BCR was a useful prognostic factor for COVID-19 patients. Development of an individualized BCR-based prediction nomogram can effectively predict the risk of mortality and help clinicians to make individual treatment early.

7.
Clin Appl Thromb Hemost ; 26: 1076029620982669, 2020.
Article in English | MEDLINE | ID: covidwho-999509

ABSTRACT

Deep venous thrombosis (DVT) is a severe complication of coronavirus disease 2019 (COVID-19). The purpose of this study was to study the prevalence, risk factors, anticoagulant therapy and sex differences of DVT in patients with COVID-19. The enrolled 121 hospitalized non-ventilator patients were confirmed positive for COVID-19. All suspected patients received color Doppler ultrasound (US) to screen for DVT in both lower extremities. Multivariate logistic regression was performed to identify risk factors related to DVT in COVID-19 patients. DVT was found in 48% of the asymptomatic COVID-19 patients with an increased PADUA or Caprini index using US scanning. The multivariate logistic regression determined that age (OR, 1.05; p = .0306), C-reactive protein (CRP) (OR, 1.02; p = .0040), and baseline D-dimer (OR, 1.42; p = .0010) were risk factors among COVID-19 patients. Although the most common DVT location was infrapopliteal (classes I and II), higher mortality in DVT-COVID-19 patients was confirmed. DVT-COVID-19 patients presented significant increases in CRP, neutrophil count, and D-dimer throughout the whole inpatient period compared to non-DVT-COVID-19 patients. Although anticoagulation therapy accelerated the recovery of lymphocytopenia in DVT patients, men DVT-COVID-19 patients with anticoagulant therapy showed significant higher CRP and neutrophil count vs. lymphocyte count (N/L) ratio, but showed lower lymphocyte counts compared to women DVT-COVID-19 patients. DVT is common in COVID-19 patients with high-risk factors, especially for older age and higher CRP and baseline D-dimer populations. It is important to consider sex differences in anticoagulant therapy among DVT-COVID-19 patients.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Venous Thrombosis/etiology , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , C-Reactive Protein/analysis , COVID-19/blood , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Sex Characteristics
9.
Int J Antimicrob Agents ; 56(3): 106110, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-663165

ABSTRACT

The crude mortality rate in critical pneumonia cases with coronavirus disease 2019 (COVID-19) reaches 49%. This study aimed to test whether levels of blood urea nitrogen (BUN) in combination with D-dimer were predictors of in-hospital mortality in COVID-19 patients. The clinical characteristics of 305 COVID-19 patients were analysed and were compared between the survivor and non-survivor groups. Of the 305 patients, 85 (27.9%) died and 220 (72.1%) were discharged from hospital. Compared with discharged cases, non-survivor cases were older and their BUN and D-dimer levels were significantly higher (P < 0.0001). Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses identified BUN and D-dimer levels as independent risk factors for poor prognosis. Kaplan-Meier analysis showed that elevated levels of BUN and D-dimer were associated with increased mortality (log-rank, P < 0.0001). The area under the curve for BUN combined with D-dimer was 0.94 (95% CI 0.90-0.97), with a sensitivity of 85% and specificity of 91%. Based on BUN and D-dimer levels on admission, a nomogram model was developed that showed good discrimination, with a concordance index of 0.94. Together, initial BUN and D-dimer levels were associated with mortality in COVID-19 patients. The combination of BUN ≥ 4.6 mmol/L and D-dimer ≥ 0.845 µg/mL appears to identify patients at high risk of in-hospital mortality, therefore it may prove to be a powerful risk assessment tool for severe COVID-19 patients.


Subject(s)
Betacoronavirus/pathogenicity , Blood Urea Nitrogen , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Fibrin Fibrinogen Degradation Products/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Aged , Area Under Curve , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk , SARS-CoV-2
10.
Clin Infect Dis ; 72(4): 652-660, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-638980

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. METHODS: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. RESULTS: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. CONCLUSIONS: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.


Subject(s)
COVID-19 , Nomograms , China/epidemiology , Humans , Prognosis , Retrospective Studies , SARS-CoV-2
11.
Trends Pharmacol Sci ; 41(8): 531-543, 2020 08.
Article in English | MEDLINE | ID: covidwho-600931

ABSTRACT

Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/virology , Pneumonia, Viral/physiopathology , Animals , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokines/immunology , Humans , Janus Kinases/metabolism , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , SARS-CoV-2 , STAT Transcription Factors/metabolism , Signal Transduction/physiology
12.
Int J Antimicrob Agents ; 55(6): 105948, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-143536

ABSTRACT

COVID-19, the disease caused by SARS-CoV-2, is a highly contagious disease. The World Health Organization has declared the ongoing outbreak to be a global public health emergency. Currently, the research on SARS-CoV-2 is in its primary stages. Based on current published evidence, this review systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of COVID-19. It is hoped that this review will help the public to recognize and deal with SARS-CoV-2, and provide a reference for future studies.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections , Pandemics , Pneumonia, Viral , Betacoronavirus/classification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Genome, Viral/genetics , Host Specificity/physiology , Humans , Immunization, Passive/methods , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Prevalence , SARS-CoV-2
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