Meta-Analysis of D-Dimer, hsCRP and Cytokines in COVID-19 Severe/Critical Patients in China

Abstract Objective: To analyze the relationship between D-dimer, inflammatory markers, cytokines and disease severity, and the possibility of early identification of COVID-19 critical type patients. Methods: PubMed, EMBASE and CNKI databases were searched by computer, and references of related reviews and systematic reviews were manually searched as supplements. The retrieval deadline is February 9, 2021. According to the inclusion and exclusion criteria, the literatures were screened and the quality was evaluated, and then the data were extracted for meta-analysis. The fixed/random effects model was used to calculate the weighted mean difference (WMD) and 95% CI to evaluate whether the levels of D-dimer, hsCRP, IL-6, IL-8, IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients. If there were statistical differences, logistic regression analysis was used, and establish the receiver operating characteristic curve (ROC) and area under the curve (AUC) of each index for the diagnosis of critical type patients. The best diagnostic value of COVID-19 critical type patients was calculated by Youden index. Results: A total of 3519 literatures entered the screening process. According to the inclusion and exclusion criteria, 40 articles were finally included in this study, and all of them were high-quality studies after evaluation. The results of meta-analysis showed that the levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in critical type group were significantly higher than those in severe type group (P<0.05). Based on ROC curve, the AUC of D-dimer was 0.785 (95% CI: 0.671-0.899), AUC of hsCRP was 0.884 (95% CI: 0.632-1.000), AUC of IL-6 was 0.819 (95% CI: 0.700-0.939), which had diagnostic significance for critical type patients (P<0.05). The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L (sensitivity 89.3%, specificity 64.0%); the optimal diagnostic threshold of hsCRP was ≥64.22 mg/L (sensitivity 75.0%, specificity 100%); the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L (sensitivity 68.0%, specificity 92.0%). Conclusion: The levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in COVID-19 critical type patients were significantly higher than those in severe type patients. Our results might be helpful in identify and risk reduction of mortality in critical types patients infected with COVID-19. Disclosures No relevant conflicts of interest to declare.

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Prevalence and risk factors of thrombotic events on patients with COVID-19: a systematic review and meta‐analysis

Thrombosis Journal ◽

10.1186/s12959-021-00284-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiaoming Xiong ◽

Jianhua Chi ◽

Qinglei Gao

Keyword(s):

Risk Factors ◽

Web Of Science ◽

Weighted Mean Difference ◽

Meta Analysis ◽

White Blood Cells ◽

Thromboembolism Prophylaxis ◽

Risk Of Death ◽

Coagulation Abnormalities ◽

Male Sex ◽

D Dimer

Abstract Background Coagulation abnormalities in COVID-19 patients accompanied with poor prognosis. This study aimed to determine the prevalence and risk factors of thrombotic events on COVID-19 patients. Methods. We systematically reviewed all the studies about thrombotic events on COVID-19 patients in PubMed, Embase, Web of Science, MedRxiv, bioRxiv, from Dec 1, 2019 to July 5, 2020. The weighted mean difference (MD) or odds ratio (OR) or relative risk (RR) with 95 % confidence intervals (CI) for clinical data in COVID-19 patients with or without thrombotic events was calculated. Results 12 articles contained 1083 patients were included for meta-analysis. The prevalence of thrombosis was 22 % (95 % CI 0.08–0.40) in COVID-19 patients and increased to 43 % (95 % CI 0.29–0.65) after admission to the intensive care unit (ICU). Compared with non-thrombotic patients, thrombotic patients had higher levels of D-dimer (MD = 2.79 μg/ml, 95 % CI 2.27–3.31 μg/ml), lactate dehydrogenase (LDH) (MD = 112.71 U/L, 95 % CI 62.40–163.02 U/L), and white blood cells (WBC) (MD = 1.14 *109/L, 95 % CI 0.47–1.81*109/L) while decreased lymphocytes (MD= -0.20*109/L, 95 % CI -0.38 – -0.02*109/L). Age, platelet counts, and male sex tended to be risks while diabetes tended to be a protection for thrombosis for COVID-19 patients, although no statistical difference was achieved. Finally, patients with thrombosis were at a higher risk of death (OR = 2.39, 95 % CI 1.36–4.20). Conclusions Prevalence of thrombosis in COVID-19 patients was high, especially in ICU, though pharmacologic thromboembolism prophylaxis was applied. Therefore, higher levels of D-dimer, LDH, WBC, and decreased lymphocytes needed to be paid close attention to in patients with COVID-19.

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Risk factors of severe cases with COVID-19: a meta-analysis

Epidemiology and Infection ◽

10.1017/s095026882000179x ◽

2020 ◽

Vol 148 ◽

Cited By ~ 5

Author(s):

Mingchun Ou ◽

Jieyun Zhu ◽

Pan Ji ◽

Hongyuan Li ◽

Zhimei Zhong ◽

...

Keyword(s):

Risk Factors ◽

Platelet Count ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Severe Disease ◽

C Reactive Protein ◽

Reactive Protein ◽

Electronic Search ◽

Low Platelet Count ◽

D Dimer

Abstract Our study aimed to systematically analyse the risk factors of coronavirus disease 2019 (COVID-19) patients with severe disease. An electronic search in eight databases to identify studies describing severe or critically ill COVID-19 patients from 1 January 2020 to 3 April 2020. In the end, we meta-analysed 40 studies involving 5872 COVID-19 patients. The average age was higher in severe COVID-19 patients (weighted mean difference; WMD = 10.69, 95%CI 7.83–13.54). Patients with severe disease showed significantly lower platelet count (WMD = −18.63, 95%CI −30.86 to −6.40) and lymphocyte count (WMD = −0.35, 95%CI −0.41 to −0.30) but higher C-reactive protein (CRP; WMD = 42.7, 95%CI 31.12–54.28), lactate dehydrogenase (LDH; WMD = 137.4, 95%CI 105.5–169.3), white blood cell count（WBC), procalcitonin（PCT）, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine（Cr）. Similarly, patients who died showed significantly higher WBC, D-dimer, ALT, AST and Cr but similar platelet count and LDH as patients who survived. These results indicate that older age, low platelet count, lymphopenia, elevated levels of LDH, ALT, AST, PCT, Cr and D-dimer are associated with severity of COVID-19 and thus could be used as early identification or even prediction of disease progression.

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Associations of D-Dimer on Admission and Clinical Features of COVID-19 Patients: A Systematic Review, Meta-Analysis, and Meta-Regression

Frontiers in Immunology ◽

10.3389/fimmu.2021.691249 ◽

2021 ◽

Vol 12 ◽

Author(s):

Runzhen Zhao ◽

Zhenlei Su ◽

Andrey A. Komissarov ◽

Shan-Lu Liu ◽

Guohua Yi ◽

...

Keyword(s):

Weighted Mean Difference ◽

Meta Analysis ◽

Case Series ◽

Alternative Interventions ◽

Clinical Variables ◽

Clinical Biomarkers ◽

Aggregate Effects ◽

Meta Regression ◽

And Gender ◽

D Dimer

BackgroundDynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists.MethodsWe performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean).FindingsThe weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase).InterpretationThese findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.

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Insufficient hyperfibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression

10.1101/2020.09.07.20190165 ◽

2020 ◽

Author(s):

Hong-Long J Ji ◽

Zhenlei Su ◽

Runzhen Zhao ◽

Andrey A Komissarov ◽

Guohua Yi ◽

...

Keyword(s):

Systematic Review ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Case Series ◽

Organ Injury ◽

Clinical Variables ◽

Clinical Biomarkers ◽

Meta Regression ◽

Meta Analyses ◽

D Dimer

Background How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. To investigate whether abnormal fibrinolysis is a culprit or protector or both, we associated elevated plasma D-dimer with clinical variables to identify a panoramic view of the derangements of fibrinolysis that contribute to the pathogenesis of COVID-19 based on studies available in the literature. Methods We performed this systematic review based on both meta-analysis and meta-regression to compute the correlation of D-dimer at admission with clinical features of COVID-19 patients in retrospective studies or case series. We searched the databases until Aug 18, 2020, with no limitations by language. The first hits were screened, data extracted, and analyzed in duplicate. We did the random-effects meta-analyses and meta-regressions (both univariate and multivariate). D-dimer associated clinical variables and potential mechanisms were schematically reasoned and graphed. Findings Our search identified 42 observational, or retrospective, or case series from six countries (n=14,862 patients) with all races and ages from 1 to 98-year-old. The weighted mean difference of D-dimer was 0.97 μg/mL (95% CI 0.65, 1.29) between relatively mild (or healthy control) and severely affected groups with significant publication bias. Univariate meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels, including 3 demographics, 5 comorbidies, 22 laboratory tests, 18 organ injury biomarkers, 8 severe complications, and 2 outcomes (discharge and death). Of these, 11 readouts were negatively associated with the level of plasma D-dimer. Further, age and gender were confounding factors for the identified D-dimer associated variables. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN, bilirubin, ALT, AST, systolic blood pressure, and CK. We thus propose that "insufficient hyperfibrinolysis (fibrinolysis is accelerated but unable to prevent adverse clinical impact for clinical deterioration COVID-19)" as a peculiar mechanism. Interpretation The findings of this meta-analysis- and meta-regression-based systematic review supports elevated D-dimer as an independent predictor for mortality and severe complications. D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and locally (i.e., in the lung) hyperactive derangements of fibrinolysis. D-dimer and associated clinical biomarkers and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.

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The association between dietary inflammatory index and risk of central obesity in adults: An updated systematic review and meta-analysis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000648 ◽

2020 ◽

Vol 90 (5-6) ◽

pp. 535-552 ◽

Cited By ~ 2

Author(s):

Mahdieh Abbasalizad Farhangi ◽

Mahdi Vajdi

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Central Obesity ◽

Assessment Tool ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Dietary Factors ◽

Cross Sectional ◽

Inflammatory Status ◽

Obesity Indices

Abstract. Backgrounds: Central obesity, as a pivotal component of metabolic syndrome is associated with numerous co-morbidities. Dietary factors influence central obesity by increased inflammatory status. However, recent studies didn’t evaluate the association between central obesity and dietary inflammation index (DII®) that give score to dietary factors according to their inflammatory potential. In the current systematic review and meta-analysis, we summarized the studies that investigated the association between DII® with central obesity indices in the general populations. Methods: In a systematic search from PubMed, SCOPUS, Web of Sciences and Cochrane electronic databases, we collected relevant studies written in English and published until 30 October 2019. The population of included studies were apparently healthy subjects or individuals with obesity or obesity-related diseases. Observational studies that evaluated the association between DII® and indices of central obesity including WC or WHR were included. Results: Totally thirty-two studies were included; thirty studies were cross-sectional and two were cohort studies with 103071 participants. Meta-analysis of observational studies showed that higher DII® scores were associated with 1.81 cm increase in WC (Pooled weighted mean difference (WMD) = 1.813; CI: 0.785–2.841; p = 0.001). Also, a non-significant increase in the odds of having higher WC (OR = 1.162; CI: 0.95–1.43; p = 0.154) in the highest DII category was also observed. In subgroup analysis, the continent, dietary assessment tool and gender were the heterogeneity sources. Conclusion: The findings proposed that adherence to diets with high DII® scores was associated with increased WC. Further studies with interventional designs are necessary to elucidate the causality inference between DII® and central obesity indices.

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D-Dimer, Disease Severity, and Deaths (3D-Study) in Patients with COVID-19: A Systematic Review and Meta-Analysis

SSRN Electronic Journal ◽

10.2139/ssrn.3696621 ◽

2020 ◽

Author(s):

Seshadri Reddy Varikasuvu ◽

Naveen Dutt ◽

Saurabh Varshney ◽

Shahir Asfahan ◽

Paresh P. Kulkarni ◽

...

Keyword(s):

Systematic Review ◽

Disease Severity ◽

Meta Analysis ◽

D Dimer

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Puerarin for OVX-Induced Postmenopausal Osteoporosis in Murine Model: Systematic Review and Meta-Analysis

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190703143946 ◽

2020 ◽

Vol 15 (1) ◽

pp. 37-42 ◽

Cited By ~ 1

Author(s):

Xiaobin Yang ◽

Haishi Zheng ◽

Yuan Liu ◽

Dingjun Hao ◽

Baorong He ◽

...

Keyword(s):

Systematic Review ◽

Bone Mass ◽

Postmenopausal Osteoporosis ◽

Murine Model ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Mean Difference ◽

Weighted Mean ◽

Enhancing Effect ◽

Searching Strategy

Aims/Background: Ovariectomy (OVX)-induced murine model is widely used for postmenopausal osteoporosis study. Our current study was conducted to systematically review and essentially quantified the bone mass enhancing effect of puerarin on treating OVX-induced postmenopausal osteoporosis in murine model. Methods: Literatures from PUBMED, EMBASE, and CNKI were involved in our searching strategy by limited the inception date to January 9th, 2019. Moreover, the enhancing effect of puerarin on bone mass compared to OVX-induced rats is evaluated by four independent reviewers. Finally, all the data were extracted, quantified and analyzed via RevMan, besides that in our current review study, we assessed the methodological quality for each involved study. Results: Based on the searching strategy, eight randomization studies were finally included in current meta-analysis and systematic review. According to the data analysis by RevMan, puerarin could improve bone mineral density (BMD); (eight studies, n=203; weighted mean difference, 0.05; 95% CI, 0.03-0.07; P<0.0001) using a random-effects model. There is no significant difference between puerarin and estrogen (seven studies, n=184; weighted mean difference, 0.00; 95% CI, -0.01 to 0.00; P=0.30). Conclusions: Puerarin showed upregulating effects on bone mass in OVX-induced postmenopausal osteoporosis in murine model. More studies of the effect of puerarin on bone density in OVX animals are needed.

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The effect of rTMS in the management of pain associated with CRPS

Translational Neuroscience ◽

10.1515/tnsci-2020-0120 ◽

2020 ◽

Vol 11 (1) ◽

pp. 363-370

Author(s):

Min Cheol Chang ◽

Sang Gyu Kwak ◽

Donghwi Park

Keyword(s):

Repetitive Transcranial Magnetic Stimulation ◽

Controlled Trial ◽

Meta Analysis ◽

Pain Syndrome ◽

Treatment Session ◽

Cochrane Library ◽

Exclusion Criteria ◽

Analgesic Effects ◽

Randomized Controlled ◽

Before And After

AbstractBackgroundTherapeutic management of pain in patients with complex regional pain syndrome (CRPS) is challenging. Repetitive transcranial magnetic stimulation (rTMS) has analgesic effects on several types of pain. However, its effect on CRPS has not been elucidated clearly. Therefore, we conducted a meta-analysis of the available clinical studies on rTMS treatment in patients with CRPS.Materials and methodsA comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases. We included studies published up to February 09, 2020, that fulfilled our inclusion and exclusion criteria. Data regarding measurement of pain using the visual analog scale before and after rTMS treatment were collected to perform the meta-analysis. The meta-analysis was performed using Comprehensive Meta-analysis Version 2.ResultsA total of three studies (one randomized controlled trial and two prospective observational studies) involving 41 patients were included in this meta-analysis. No significant reduction in pain was observed immediately after one rTMS treatment session or immediately after the entire schedule of rTMS treatment sessions (5 or 10 sessions; P > 0.05). However, pain significantly reduced 1 week after the entire schedule of rTMS sessions (P < 0.001).ConclusionrTMS appears to have a functional analgesic effect in patients with CRPS.

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Convalescent plasma therapy for COVID-19 patients: a protocol of a prospective meta-analysis of randomized controlled trials

Trials ◽

10.1186/s13063-021-05066-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lajos Szakó ◽

Nelli Farkas ◽

Szabolcs Kiss ◽

Szilárd Váncsa ◽

Noémi Zádori ◽

...

Keyword(s):

Confidence Interval ◽

Randomized Controlled Trials ◽

Organ Failure ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Plasma Therapy ◽

Monthly Basis ◽

Randomized Controlled

Abstract Background Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. Methods A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. Discussion Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.

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Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0369 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1021-1028 ◽

Cited By ~ 297

Author(s):

Brandon Michael Henry ◽

Maria Helena Santos de Oliveira ◽

Stefanie Benoit ◽

Mario Plebani ◽

Giuseppe Lippi

Keyword(s):

Serum Ferritin ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Severe Disease ◽

Severe Illness ◽

China National Knowledge Infrastructure ◽

Discriminative Ability ◽

Laboratory Findings ◽

Liver And Kidney ◽

Wbc Count

AbstractBackgroundAs coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19.MethodsAn electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter.ResultsA total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease.ConclusionsSeveral biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.

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