Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19.
ABSTRACT: BACKGROUND:Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS:In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS:Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P?
Project description:Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.
Project description:<h4>Background</h4>The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients. Here, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients.<h4>Methods</h4>A literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI).<h4>Results</h4>A total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72-1.04; I<sup>2</sup> = 75.52% and 1.87; 95%CI 1.25-2.49; I<sup>2</sup> = 97.81%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.74 (95%CI 0.98-7.66).<h4>Conclusion</h4>High NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.
Project description:Background:As the pandemic of coronavirus disease 2019 (COVID-19) continues, prognostic markers are now being identified. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily accessible values that have been known to correlate with inflammation and prognosis in several conditions. We used the available data to identify the association of NLR and PLR with the severity of COVID-19. Methods:A literature search using EMBASE, MEDLINE, and Google Scholar for studies reporting the use of NLR and PLR in COVID-19 published until April 28, 2020, was performed. Random effects meta-analysis was done to estimate standard mean difference (SMD) of NLR and PLR values with 95% confidence interval (CI) between severe and non-severe COVID-19 cases. Results:A total of 20 studies with 3,508 patients were included. Nineteen studies reported NLR values, while five studies reported PLR values between severe and non-severe COVID-19 patients. Higher levels of NLR (SMD: 2.80, 95% CI: 2.12 - 3.48, P < 0.00001) and PLR (SMD: 1.82, 95% CI: 1.03 - 2.61, P < 0.00001)) were seen in patients with severe disease compared to non-severe disease. Conclusions:NLR and PLR can be used as independent prognostic markers of disease severity in COVID-19.
Project description:<h4>Background</h4>Coronavirus disease 2019 (COVID-19), a highly infectious disease, has been rapidly spreading all over the world and remains a great threat to global public health. Patients diagnosed with severe or critical cases have a poor prognosis. Hence, it is crucial for us to identify potentially severe or critical cases early and give timely treatments for targeted patients. In the clinical practice of treating patients with COVID-19, we have observed that the neutrophil-to-lymphocyte ratio (NLR) of severe patients is higher than that in mild patients. We performed this systematic review and meta-analysis to evaluate the predictive values of NLR on disease severity and mortality in patients with COVID-19.<h4>Methods</h4>We searched PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases to identify eligible studies (up to August 11, 2020). Two authors independently screened studies and extracted data. The methodological quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).<h4>Results</h4>Thirteen studies involving 1579 patients reported the predictive value of NLR on disease severity. The pooled sensitivity (SEN), specificity (SPE) and area under curve (AUC) were 0.78 (95% CI 0.70-0.84), 0.78 (95% CI 0.73-0.83) and 0.85 (95% CI 0.81-0.88), respectively. Ten studies involving 2967 patients reported the predictive value of NLR on mortality. The pooled SEN, SPE and AUC were 0.83 (95% CI 0.75-0.89), 0.83 (95% CI 0.74-0.89) and 0.90 (95% CI 0.87-0.92), respectively.<h4>Conclusions</h4>NLR has good predictive values on disease severity and mortality in patients with COVID-19 infection. Evaluating NLR can help clinicians identify potentially severe cases early, conduct early triage and initiate effective management in time, which may reduce the overall mortality of COVID-19.<h4>Trial registry</h4>This meta-analysis was prospectively registered on PROSPERO database (Registration number: CRD42020203612).
Project description:<b>Objective:</b> Examine the possible beneficial effects of early, D-dimer driven anticoagulation in preventing thrombotic complications and improving the overall outcomes of COVID-19 intubated patients. <b>Methods:</b> To address COVID-19 hypercoagulability, we developed a clinical protocol to escalate anticoagulation based on serum D-dimer levels. We retrospectively reviewed all our first 240 intubated patients with COVID-19. Of the 240, 195 were stratified into patients treated based on this protocol (ON-protocol, <i>n</i> = 91) and the control group, patients who received standard thromboprophylaxis (OFF-protocol, <i>n</i> = 104). All patients were admitted to the Stony Brook University Hospital intensive care units (ICUs) between February 7th, 2020 and May 17, 2020 and were otherwise treated in the same manner for all aspects of COVID-19 disease. <b>Results:</b> We found that the overall mortality was significantly lower ON-protocol compared to OFF-protocol (27.47 vs. 58.66%, <i>P</i> < 0.001). Average maximum D-dimer levels were significantly lower in the ON-protocol group (7,553 vs. 12,343 ng/mL), as was serum creatinine (2.2 vs. 2.8 mg/dL). Patients with poorly controlled D-dimer levels had higher rates of kidney dysfunction and mortality. Transfusion requirements and serious bleeding events were similar between groups. To address any possible between-group differences, we performed a propensity-matched analysis of 124 of the subjects (62 matched pairs, ON-protocol and OFF-protocol), which showed similar findings (31 vs. 57% overall mortality in the ON-protocol and OFF-protocol group, respectively). <b>Conclusions:</b> D-dimer-driven anticoagulation appears to be safe in patients with COVID-19 infection and is associated with improved survival. <b>What This Paper Adds:</b> It has been shown that hypercoagulability in patients with severe COVID-19 infection leads to thromboembolic complications and organ dysfunction. Anticoagulation has been variably administered to these patients, but it is unknown whether routine or escalated thromboprophylaxis provides a survival benefit. Our data shows that escalated D-dimer driven anticoagulation is associated with improved organ function and overall survival in intubated COVID-19 ICU patients at our institution. Importantly, we found that timely escalation of this anticoagulation is critical in preventing organ dysfunction and mortality in patients with severe COVID-19 infection.
Project description:Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 109/L, lymphocyte count<1 × 109/L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 109/L: OR = 2.92, 95% CI: 1.96-4.35; lymphocyte count<1 × 109/L: OR = 4.97, 95% CI: 3.53-6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97-10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38-5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04-3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.
Project description:INTRODUCTION:Patients with severe COVID-19 can develop ventilator-dependent acute hypoxic respiratory failure (VDAHRF), which is associated with a higher mortality rate. We evaluated the clinical course of hospitalized COVID-19 patients and compared them with the patients who received invasive mechanical ventilation. Characteristics of intubated patients who were successfully weaned from the ventilator were compared with the patients who failed to be extubated or died in the hospital. OBJECTIVE:To investigate the clinical course of hospitalized COVID-19 patients, and assess the possible predictors of the disease severity leading to VDAHRF. METHODS:This is a single-center, retrospective study. The first 129 patients (18 years or older) with COVID-19 admitted to Monmouth Medical Center from March 1st to April 25th, 2020 were included. RESULTS:Out of 129 patients, 23.25% (n = 30) required invasive mechanical ventilation, and of those, six patients were successfully weaned from the ventilator. Multivariable logistic regression analysis showed increased odds of intubation associated with hypoxemia (odds ratio 17.23, 95% CI 5.206-57.088; p < 0.0001), elevated d-dimer by one unit mg/L of FEU (odds ratio 1.515, 95% CI 5.206-57.088; p = 0.0430) and elevated ferritin by one unit ng/ml (odds ratio 1.001, 95% CI 1.000-1.001, p = 0.0051) on admission, adjusted for other covariates. CONCLUSIONS:Patients who required invasive mechanical ventilation were more likely to have older age, male gender, coronary artery disease, diabetes, and obesity. The patients who were successfully weaned from the ventilator were more likely to be younger in age, and none of them had heart failure or CAD.
Project description:Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.
Project description:OBJECTIVE:Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS:All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS:Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS:Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.
Project description:BACKGROUND:Complications of coronavirus disease 2019 (COVID-19) include coagulopathy. We performed a meta-analysis on the association of COVID-19 severity with changes in hemostatic parameters. METHODS:Data on prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer, platelets (PLT), or fibrinogen in severe versus mild COVID-19 patients, and/or in non-survivors to COVID-19 versus survivors were systematically searched. The standardized mean difference (SMD) was calculated. RESULTS:Sixty studies comparing 5487 subjects with severe and 9670 subjects with mild COVID-19 documented higher PT (SMD: 0.41; 95%CI: 0.21, 0.60), D-Dimer (SMD: 0.67; 95%CI: 0.52, 0.82), and fibrinogen values (SMD: 1.84; 95%CI: 1.21, 2.47), with lower PLT count (SMD: -0.74; 95%CI: -1.01, -0.47) among severe patients. Twenty-five studies on 1511 COVID-19 non-survivors and 6287 survivors showed higher PT (SMD: 0.67; 95%CI: 0.39, 0.96) and D-Dimer values (SMD: 3.88; 95%CI: 2.70, 5.07), with lower PLT count (SMD: -0.60, 95%CI: -0.82, -0.38) among non-survivors. Regression models showed that C-reactive protein values were directly correlated with the difference in PT and fibrinogen. CONCLUSIONS:Significant hemostatic changes are associated with COVID-19 severity. Considering the risk of fatal complications with residual chronic disability and poor long-term outcomes, further studies should investigate the prognostic role of hemostatic parameters in COVID-19 patients.