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

2020 ◽  
Vol 58 (7) ◽  
pp. 1021-1028 ◽  
Author(s):  
Brandon Michael Henry ◽  
Maria Helena Santos de Oliveira ◽  
Stefanie Benoit ◽  
Mario Plebani ◽  
Giuseppe Lippi

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.

2021 ◽  
Vol 8 ◽  
Author(s):  
Chaoqun Ma ◽  
Dingyuan Tu ◽  
Jiawei Gu ◽  
Qiang Xu ◽  
Pan Hou ◽  
...  

Objective: Cardiac injury is detected in numerous patients with coronavirus disease 2019 (COVID-19) and has been demonstrated to be closely related to poor outcomes. However, an optimal cardiac biomarker for predicting COVID-19 prognosis has not been identified.Methods: The PubMed, Web of Science, and Embase databases were searched for published articles between December 1, 2019 and September 8, 2021. Eligible studies that examined the anomalies of different cardiac biomarkers in patients with COVID-19 were included. The prevalence and odds ratios (ORs) were extracted. Summary estimates and the corresponding 95% confidence intervals (95% CIs) were obtained through meta-analyses.Results: A total of 63 studies, with 64,319 patients with COVID-19, were enrolled in this meta-analysis. The prevalence of elevated cardiac troponin I (cTnI) and myoglobin (Mb) in the general population with COVID-19 was 22.9 (19–27%) and 13.5% (10.6–16.4%), respectively. However, the presence of elevated Mb was more common than elevated cTnI in patients with severe COVID-19 [37.7 (23.3–52.1%) vs.30.7% (24.7–37.1%)]. Moreover, compared with cTnI, the elevation of Mb also demonstrated tendency of higher correlation with case-severity rate (Mb, r = 13.9 vs. cTnI, r = 3.93) and case-fatality rate (Mb, r = 15.42 vs. cTnI, r = 3.04). Notably, elevated Mb level was also associated with higher odds of severe illness [Mb, OR = 13.75 (10.2–18.54) vs. cTnI, OR = 7.06 (3.94–12.65)] and mortality [Mb, OR = 13.49 (9.3–19.58) vs. cTnI, OR = 7.75 (4.4–13.66)] than cTnI.Conclusions: Patients with COVID-19 and elevated Mb levels are at significantly higher risk of severe disease and mortality. Elevation of Mb may serve as a marker for predicting COVID-19-related adverse outcomes.Prospero Registration Number:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020175133, CRD42020175133.


Author(s):  
Furong Zeng ◽  
Ying Guo ◽  
Mingzhu Yin ◽  
Xiang Chen ◽  
Guangtong Deng

AbstractBackgroundThe ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction.AimsIn the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19.MethodsThe following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models.ResultsA total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, - 31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL- 6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = - 8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [- 625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment.ConclusionsThe meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039898
Author(s):  
Weijing Fan ◽  
Baozhong Yang ◽  
Xiaoming Hu ◽  
Xiao Yang ◽  
Chenyan Shi ◽  
...  

IntroductionLeg ulcers (LUs) not only seriously affect life and work of patients, but also bring huge economic burden to the society. As a potential underused biological debridement, larval therapy provides help for the treatment of LUs. The purpose of our research is to assess whether patients with LUs can benefit from larval therapy.Methods and analysisThe following electronic databases will be searched: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure Database, Wanfang Database and Chinese Biological Medicine. Randomised controlled trials are eligible for inclusion. There will be no restrictions with respect to language and search date is up to June 2020. Primary outcomes investigated are complete healing rate after treatment, time to ulcer healing, reduction of wound surface area and adverse events. Risk ratios will be used for categorical data; weighted mean difference will be used for measurement data. Subgroup analysis and sensitivity analysis will be considered if heterogeneity exists. The results of data synthesis will be performed by narrative summary and quantitative analysis.Ethics and disseminationThis systematic review does not require the approval of the ethics committee because individual data on patients are not collected. The results of the study will be disseminated in peer-reviewed journals.PROSPERO registration numberCRD42020176953.


2020 ◽  
Author(s):  
Alberto Polimeni ◽  
Isabella Leo ◽  
Carmen Spaccarotella ◽  
Annalisa Mongiardo ◽  
Sabato Sorrentino ◽  
...  

Abstract Coronavirus Disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH-criteria for disseminated intravascular coagulopathy (DIC). We conducted a meta-analysis of all available studies on COVID-19 to explore the impact of coagulopathy on severe illness and mortality. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. The primary analysis showed that mean d-dimer is significantly higher in COVID-19 patients with severe disease than in those without (SMD -2.15 [-2.73 to -1.56], I2 98%, P <0.0001). Additional analysis of platelet count showed lower levels of mean PLT in Severe patients than those observed in the Non-Severe patients (SMD 0.77 [0.32 to 1.22], I2 96%, P <0.001). Interestingly, longer mean PT was found in Severe group (SMD -1.34 [-2.06 to -0.62], I2 98%, P <0.0002) compared to Non-Severe group. In conclusion, the results of the present meta-analysis, the largest and most comprehensive to date, demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT.


2020 ◽  
Vol 66 (2) ◽  
pp. 227-231
Author(s):  
Shuang Wen ◽  
Liu Yang ◽  
Lianping He ◽  
Changwei Liu

SUMMARY BACKGROUND An association between increased serum ferritin levels and acute myocardial infarction (AMI) remains controversial. The purpose of this meta-analysis is to confirm the association between increased serum ferritin levels and AMI. METHODS We searched PubMed and China National Knowledge Infrastructure (CNKI) for relevant articles that assessed the association between serum ferritin and acute myocardial infarction using terms that included serum ferritin and acute myocardial infarction up to February 13, 2019. RESULTS A total of 11 studies were identified for analysis. All pooled analysis was based on a random-effects models. The variance was exhibited using a forest plot, and the heterogeneity among studies was examined using the I2 index, the publication bias was evaluated using a funnel plot. The pooled standard mean difference of ferritin levels between AMI and controls was 0.78 (95%CI,0.68-0.88). CONCLUSION The results of this meta-analysis demonstrate that serum ferritin in acute myocardial infarction patients is higher than that of healthy controls.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Hu ◽  
Yuwei Zhu ◽  
Fangfang Zhou ◽  
Cuiying Peng ◽  
Zhiping Hu ◽  
...  

Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH.Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD).Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models.Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1049-1049 ◽  
Author(s):  
Nao Yoshida ◽  
Hiroshi Yagasaki ◽  
Yoshiyuki Kosaka ◽  
Ryoji Kobayashi ◽  
Hiromasa Yabe ◽  
...  

Abstract Aplastic anemia (AA) is defined as a pancytopenia caused by bone marrow failure; its pathogenesis is thought to involve autoimmune processes. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CyA) provides response rates of 50–70% for children with AA, but predictive markers of response to therapy have not been well defined. We previously investigated the clinical relevance of HLA, a minor population of paroxysmal nocturnal hemoglobinuria-type cells, and a specific auto-antibody associated with AA in pediatric patients and reported that there was no correlation between these markers and response to therapy (Yoshida N, et al. Br J Haematol, 2008). In the current study, we prospectively evaluated whether clinical and laboratory findings before treatment, including age, sex, interval between diagnosis and treatment, etiology, severity of disease, white blood cell (WBC) count, neutrophil count, hemoglobin level, reticulocyte count, and platelet count, could predict the IST response at 6 months. Subjects included a large population of pediatric AA patients enrolled in a multicenter AA-97 study conducted by the Japan Childhood Aplastic Anemia Study Group. Between October 1997 and September 2006, 312 children (186 boys and 126 girls) younger than 18 years who were newly diagnosed with AA were enrolled in the study and treated with a combination of ATG and CyA. The median age at diagnosis was 8 years (range, 1–17 years). Of the 312 patients, 261 had idiopathic AA, 44 had hepatitis-associated AA, and 7 had AA from other causes. In terms of severity, 156 patients had very severe disease, 107 had severe disease, and 49 had moderate disease. The median interval between diagnosis and treatment was 15 days (range, 1–180 days). The overall response rate was 56%. In multivariate analyses, lower WBC count, shorter interval between diagnosis and therapy, and male sex were predictive markers of better response. Patients with WBC &lt;2500/μl had a significantly higher response rate than those with WBC ≥2500/μl (61 vs. 48%; P=0.008); this was the strongest predictor of response. Notably, response rate was inversely related to the interval between diagnosis and treatment; response rates of patients with an interval between diagnosis and treatment of &lt;30 and ≥30 days were 60% and 43%, respectively (P=0.02). Boys had a better response compared with girls (62 vs. 48%; P=0.02). In conclusion, pretreatment clinical and laboratory findings influence the response rate to IST. Response is well correlated with WBC count rather than neutrophil count or severity of disease. IST should be started as soon as possible after diagnosis of AA, given that the response rate worsens as the interval between diagnosis and treatment increases.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256429
Author(s):  
Xuqin Du ◽  
Lipeng Shi ◽  
Wenfu Cao ◽  
Biao Zuo ◽  
Aimin Zhou

Introduction Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China’s experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. Methods Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. Results Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. Conclusion Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.


2021 ◽  
Vol 8 ◽  
Author(s):  
Angelo Zinellu ◽  
Arduino A. Mangoni

Excessive inflammation and malnutrition are associated with coronavirus disease 2019 (COVID-19) severity and mortality. Combined biomarkers of malnutrition and inflammation, such as serum prealbumin, might be particularly attractive for early risk stratification. We conducted a systematic review and meta-analysis of studies reporting serum prealbumin in patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January and November 2020, for studies reporting data on serum prealbumin, COVID-19 severity, defined as severe illness, prolonged viral load, receiving mechanical ventilation or admitted to intensive care unit (ICU), and mortality. Nineteen studies in 4,616 COVID-19 patients were included in the meta-analysis. Pooled results showed that serum prealbumin concentrations were significantly lower in patients with severe disease and non-survivors (standard mean difference, SMD, −0.92, 95% CI, −1.10 to −0.74, P &lt; 0.001). Extreme heterogeneity was observed (I2 = 77.9%; P &lt; 0.001). In sensitivity analysis, the effect size was not significantly affected when each study was in turn removed (range between −0.86 and −0.95). The Begg's (P = 0.06) and Egger's t-tests (P = 0.26) did not show publication bias. Pooled SMD values were significantly and negatively associated with age (t = −2.18, P = 0.045) and C-reactive protein (t = −3.85, P = 0.002). In our meta-analysis, lower serum prealbumin concentrations were significantly associated with COVID-19 severity and mortality. This combined marker of malnutrition and inflammation might assist with early risk stratification and management in this group.


2020 ◽  
Vol 148 ◽  
Author(s):  
Mingchun Ou ◽  
Jieyun Zhu ◽  
Pan Ji ◽  
Hongyuan Li ◽  
Zhimei Zhong ◽  
...  

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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