Prognostic Impact of Coagulopathy in Patients with COVID-19: a Meta-analysis of 35 Studies and 6427 Patients

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.

[1]  C. Whyte,et al.  Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19 , 2020, Journal of Thrombosis and Haemostasis.

[2]  Qing Zhou,et al.  Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China , 2020, International Journal of Cardiology.

[3]  G. Lippi,et al.  D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis , 2020, Thrombosis and Haemostasis.

[4]  Xilong Deng,et al.  Prognostic Factors for COVID-19 Pneumonia Progression to Severe Symptoms Based on Earlier Clinical Features: A Retrospective Analysis , 2020, Frontiers in Medicine.

[5]  G. Zhen,et al.  Radiographic Findings and other Predictors in Adults with Covid-19 , 2020, medRxiv.

[6]  Y. Hu,et al.  A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China , 2020, medRxiv.

[7]  Hui Guo,et al.  Risk-adapted Treatment Strategy For COVID-19 Patients , 2020, International Journal of Infectious Diseases.

[8]  Dengju Li,et al.  Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy , 2020, Journal of Thrombosis and Haemostasis.

[9]  Lanjuan Li,et al.  Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID‐19) , 2020, Journal of internal medicine.

[10]  Ke Ma,et al.  Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study , 2020, BMJ.

[11]  Z. Hong,et al.  Clinical Features and Risk Factors for the Severity of Inpatients with COVID-19: A Retrospective Cohort Study , 2020 .

[12]  K. Cheng,et al.  Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study , 2020, medRxiv.

[13]  T. Guo,et al.  Characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan, China , 2020, medRxiv.

[14]  Zhi-heng Liu,et al.  COVID-19 Myocarditis and Severity Factors: An Adult Cohort Study , 2020, medRxiv.

[15]  Y. Xiong,et al.  Clinical features and treatment of COVID‐19 patients in northeast Chongqing , 2020, Journal of medical virology.

[16]  Zhicheng Zhang,et al.  Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. , 2020, Annals of palliative medicine.

[17]  R. Liu,et al.  Prominent changes in blood coagulation of patients with SARS-CoV-2 infection , 2020, Clinical chemistry and laboratory medicine.

[18]  Hong Jiang,et al.  Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up , 2020, Journal of Infection.

[19]  G. Duan,et al.  Kidney Dysfunctions of COVID-19 Patients: A Multi-Centered, Retrospective, Observational Study , 2020 .

[20]  M. Li,et al.  Leukopenia Predicts Risk for Death in Critically Ill Patients with COVID-19 in Wuhan, China: A Single-Centered, Retrospective Study , 2020 .

[21]  Changfeng Dong,et al.  Clinical Characteristics and Cardiac Injury Description of 419 Cases of COVID-19 in Shenzhen, China , 2020 .

[22]  Wei Liu,et al.  Exploring the Law of Development and Prognostic Factors of Common and Severe COVID-19: A Retrospective Case-Control Study in 122 Patients with Complete Course of Disease , 2020 .

[23]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[24]  Q. Zeng,et al.  Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population , 2020, medRxiv.

[25]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[26]  C. Shi,et al.  Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series , 2020, medRxiv.

[27]  Hongzhou Lu,et al.  A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention , 2020, medRxiv.

[28]  C. Akdis,et al.  Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China , 2020, Allergy.

[29]  Dengju Li,et al.  Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia , 2020, Journal of Thrombosis and Haemostasis.

[30]  Lei Liu,et al.  COVID‐19 in a designated infectious diseases hospital outside Hubei Province, China , 2020, medRxiv.

[31]  Lijuan Xiong,et al.  Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients , 2020, EBioMedicine.

[32]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[33]  G. Gao,et al.  A Novel Coronavirus from Patients with Pneumonia in China, 2019 , 2020, The New England journal of medicine.

[34]  Dennis Andersson,et al.  A retrospective cohort study , 2018 .

[35]  C. Indolfi,et al.  Diagnostic Performance of the Instantaneous Wave-Free Ratio: Comparison With Fractional Flow Reserve , 2018, Circulation. Cardiovascular interventions.

[36]  C. Indolfi,et al.  Long-term outcomes of coronary artery bypass grafting versus stent-PCI for unprotected left main disease: a meta-analysis , 2017, BMC Cardiovascular Disorders.

[37]  Chao Lu,et al.  Retrospective study , 2016, Medicine.

[38]  C. Indolfi,et al.  Impact of intracoronary adenosine administration during primary PCI: A meta-analysis. , 2016, International journal of cardiology.

[39]  C. Indolfi,et al.  Clinical and Procedural Outcomes of 5-French versus 6-French Sheaths in Transradial Coronary Interventions , 2015, Medicine.

[40]  Jiming Liu,et al.  Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range , 2014, BMC Medical Research Methodology.

[41]  F. Schmidt Meta-Analysis , 2008 .