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Anticoagulation in COVID-19: A Systematic Review, Meta-analysis, and Rapid Guidance From Mayo Clinic

      Abstract

      A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.

      Abbreviationsand Acronyms:

      aPTT (activated thromboplastin time), COVID-19 (coronavirus disease 2019), DIC (disseminated intravascular coagulation), DOAC (direct oral anticoagulant), DVT (deep venous thrombosis), ICU (intensive care unit), LMWH (low-molecular-weight heparin), OR (odds ratio), PE (pulmonary embolism), PT (prothrombin time), SARS-CoV (severe acute respiratory syndrome coronavirus), SC (subcutaneously), VTE (venous thromboembolism)
      Severe acute respiratory syndrome coronavirus (SARS-CoV) 2 causing coronavirus disease 2019 (COVID-19) has infected more than 5.5 million individuals worldwide and caused more than 350,000 deaths.
      Johns Hopkins University
      COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University.
      In the United States, there have been nearly 1.7 million confirmed cases and nearly 100,000 deaths.
      Johns Hopkins University
      COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University.
      ,
      Centers for Disease Control and Prevention
      The Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET).
      A prominently described feature of this disease has been its hematologic manifestations and high risk of thrombosis. The COVID-19 laboratory signature includes lymphopenia, neutrophilia, and thrombocytopenia with elevated fibrinogen and fibrin degradation products (D-dimer). This signature is similar to that of previous coronavirus outbreaks including SARS-CoV-1 in China in 2002 and the Middle East respiratory syndrome coronavirus in 2012.
      • Rota P.A.
      • Oberste M.S.
      • Monroe S.S.
      • et al.
      Characterization of a novel coronavirus associated with severe acute respiratory syndrome.
      • Christian M.D.
      • Poutanen S.M.
      • Loutfy M.R.
      • Muller M.P.
      • Low D.E.
      Severe acute respiratory syndrome.
      • Zaki A.M.
      • van Boheemen S.
      • Bestebroer T.M.
      • Osterhaus A.D.M.E.
      • Fouchier R.A.M.
      Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia [published correction appears in N Engl J Med. 2013;369(4):394].
      • Wong R.S.M.
      • Wu A.
      • To K.F.
      • et al.
      Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis.
      • Giannis D.
      • Ziogas I.A.
      • Gianni P.
      Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past.
      The International Society on Thrombosis and Haemostasis diagnostic criteria for overt disseminated intravascular coagulation (DIC)
      • Taylor Jr., F.B.
      • Toh C.H.
      • Hoots W.K.
      • Wada H.
      • Levi M.
      Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.
      included a category of coagulopathy associated with sepsis termed sepsis-induced coagulopathy.
      • Iba T.
      • Levy J.H.
      • Warkentin T.E.
      • Thachil J.
      • van der Poll T.
      • Levi M.
      Scientific and Standardization Committee on DIC, and the Scientific and Standardization Committee on Perioperative and Critical Care of the International Society on Thrombosis and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation.
      Coagulopathy in SARS-CoV-2 has distinctive features including elevated fibrinogen levels with only modest thrombocytopenia despite marked elevations in fibrin D-dimer values, prompting some investigators to prefer the term COVID-19–associated coagulopathy. Thrombotic outcomes include an apparent increase in the incidence of venous thromboembolism (VTE). However, many questions remain regarding a true difference and contributing factors when compared with critically ill patients without COVID-19. In the intensive care unit (ICU) setting, VTE has often been described as occurring despite heparin prophylaxis and, in some cases, in the presence of therapeutic anticoagulation.
      Although our understanding of the hematologic manifestations of COVID-19 remains in its early stages, this systematic review aims to provide a summary of current estimates of VTE risk, review anticipated laboratory values and their association with poor outcomes, discuss benefits and harms of anticoagulation, and provide suggestions for the prevention and management of this infection in patients who require hospitalization.

      Methods

      The present review follows the recommendations by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
      and was designed to provide a description of coagulopathy and the role of anticoagulants in patients with COVID-19. The analytic framework is described in Figure 1. The review was conducted by the Mayo Clinic Evidence-based Practice Center.
      Figure thumbnail gr1
      Figure 1Analytic framework for the study. COVID-19 = coronavirus disease 2019.
      Based on the evidence summarized in the systematic review, experts in thrombosis, pulmonary and critical care medicine, hematology, and cardiovascular medicine developed guidance for clinical practice. The guidance was achieved via consensus of this multidisciplinary group following critical review of the literature, available clinical experience, and serial discussions. This guidance is intended to help clinicians managing patients with COVID-19 in a large multi-state health system.

       Eligibility

      We included primary studies—prospective and retrospective—in patients with COVID-19 that reported on at least one of the following: (1) frequency of coagulation abnormalities, (2) laboratory values of coagulation parameters, and (3) efficacy of pharmacological anticoagulation. We excluded studies with less than 100 participants that only reported the prevalence of coagulopathy without an intervention. Outcomes of interest were mortality, VTE, DIC, and major bleeding.

       Literature Search and Data Extraction

      The framework for conducting reviews about the COVID-19 pandemic has been published elsewhere.
      • Murad M.H.
      • Nayfeh T.
      • Urtecho Suarez M.
      • et al.
      A framework for evidence synthesis programs to respond to a pandemic.
      A medical librarian and the methodology team designed a systematic search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, and Ovid EMBASE from the first outbreak in November, 2019, through May 1, 2020, without any language restrictions (Supplemental Table 1, available online at http://www.mayoclinicproceedings.org). We complemented the search by cross-referencing relevant systematic and rapid reviews identified by our search. Eight reviewers assessed each study for eligibility (V.D.T.R., T.N., M.U.S., S.S., R.B., M.F., T.J., M.A.), first by examining the abstracts and subsequently the full text of articles deemed potentially eligible. Both screening and data extraction were performed in a single-reviewer fashion.
      We extracted study characteristics (eg, study design, setting) and population description (eg, target population, age range, number hospitalized vs ICU). Laboratory data were extracted as either binary (eg, presence of thrombocytopenia) or continuous using means and SDs. If not available, SDs were imputed from interquartile ranges. The number of reported VTE and DIC events was also extracted. Severity of disease was categorized as mild, moderate, severe, or critical according to the description provided in each publication. Mild disease includes low-grade fever (<38°C) with few symptoms and no imaging findings of pneumonia. Moderate disease includes fever, respiratory symptoms, and imaging features of pneumonia. Severe disease includes evidence of respiratory distress (respiratory rate ≥30 breaths/min, oxygen saturation <93% at rest, PaO2/fraction of inspired oxygen ≤300 mm Hg); critical disease severity includes respiratory failure with the need for mechanical assistance, shock, and/or extrapulmonary organ failure requiring ICU management.
      • Zu Z.Y.
      • Jiang M.D.
      • Xu P.P.
      • et al.
      Coronavirus disease 2019 (COVID-19): a perspective from China.
      The system of disease severity, however, may not have been consistent across publications.
      Information regarding reporting related to risk of bias at study level was extracted separately for comparative and single-arm studies (Supplemental Tables 2 and 3, available online at http://www.mayoclinicproceedings.org). Domains evaluated include representativeness of the cohorts, ascertainment of exposure and outcomes, comparability, causality, reporting, and loss of follow-up.

       Data Synthesis

      When feasible, we conducted meta-analysis using the DerSimonian-Laird random effects model to calculate an overall proportion or a summary estimate of means. Heterogeneity was assessed using the I2 value, defining low heterogeneity as I2 lower than 50%, moderate heterogeneity as I2 between 50% and 75%, and high heterogeneity as I2 higher than 75%. We used the open-source R Project software for all statistical computing. We opted to divide patients with mild and moderate disease from those with severe and critical disease. Similarly, we compared the data of survivors to nonsurvivors. We then calculated odds ratios (ORs) and 95% CIs to evaluate the association of severity and survivorship with coagulopathy using binary data. When meta-analysis was not possible, data were synthesized narratively.

      Results

       Study Characteristics

      Of the 4070 unique citations identified, we included 37 studies (Table 1). Of these studies, 36 were retrospective studies; 8 were conducted in the ICU setting,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Klok F.A.
      • Kruip M.J.H.A.
      • van der Meer N.J.M.
      • et al.
      Incidence of thrombotic complications in critically ill ICU patients with COVID-19.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Poissy J.
      • Goutay J.
      • Caplan M.
      • et al.
      Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence [letter].
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      29 in nonspecific inpatient settings,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      • Chen R.
      • Liang W.
      • Jiang M.
      • et al.
      Medical Treatment Expert Group for COVID-19. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China.
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      • Li X.
      • Xu S.
      • Yu M.
      • et al.
      Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      ,
      • Lodigiani C.
      • Iapichino G.
      • Carenzo L.
      • et al.
      Humanitas COVID-19 Task Force
      Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
      ,
      • Paranjpe I.
      • Fuster V.
      • Lala A.
      • et al.
      Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19 [letter].
      ,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Tang N.
      • Bai H.
      • Chen X.
      • Gong J.
      • Li D.
      • Sun Z.
      Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      • Wan S.
      • Yi Q.
      • Fan S.
      • et al.
      Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients.
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      • Wang K.
      • Zhang Z.
      • Yu M.
      • Tao Y.
      • Xie M.
      15-Day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study [letter].
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      • Yin S.
      • Huang M.
      • Li D.
      • Tang N.
      Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 [published online ahead of print April 3, 2020].
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      and none in an outpatient setting. The studies were from 6 countries with the majority (28 of 37) from China, followed by France (3), Italy (2), the Netherlands (2), Ireland (1), and the United States (1). Cohorts ranged from 24 to 2773 patients with confirmed COVID-19. Overall mortality was as high as 56%. We found no studies reporting data on patients who were receiving long-term anticoagulation.
      Table 1Study Characteristics
      COVID-19 = coronavirus disease 2019; CT = computed tomography; ICU = intensive care unit.
      ,
      Continuous variables (eg, age) were summarized as mean ± SD.
      Reference, yearStudy design, countrySettingNo. of patientsTarget populationPopulation characteristicsOverall mortality
      Beun et al,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      2020
      Observational retrospective, NetherlandsICU75Patients with COVID-19100% Admitted to the ICUNot reported
      Cao et al,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      2020
      Observational retrospective, ChinaHospitalized102Patients with COVID-19Patients aged 54±22.20 y, 48% female, 17.6% admitted to the ICU16.7%
      Chen et al,
      • Chen R.
      • Liang W.
      • Jiang M.
      • et al.
      Medical Treatment Expert Group for COVID-19. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China.
      2020
      Observational retrospective, ChinaHospitalized1590Patients with COVID-19Patients aged 48.7±15.80 y, 42% female, 6.22% admitted to the ICU3.1%
      Chen et al,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      2020
      Observational retrospective, ChinaHospitalized203Severely or critically ill patients with COVID-19Patients aged 54±52.6 y, 46.8% female, 36% serious, 16.7% critical12.8%
      Gong et al,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      2020
      Observational retrospective, ChinaHospitalized189Patients with severe and nonsevere COVID-19Patients aged 48±20.7 y, 53% female, 14.8% severeNot reported
      He et al,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      2020
      Observational retrospective, ChinaHospitalized204Patients with severe and nonsevere COVID-19Patients aged 49±20.7 y, 61% female, 33.8% severe12.7%
      Klok et al,
      • Klok F.A.
      • Kruip M.J.H.A.
      • van der Meer N.J.M.
      • et al.
      Incidence of thrombotic complications in critically ill ICU patients with COVID-19.
      2020
      Observational retrospective, NetherlandsICU184Patients with COVID-19 who received thromboprophylaxisPatients aged 64±12 y, 24% female, 9.2% in therapeutic anticoagulation at admission13%
      Léonard-Lorant et al,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      2020
      Observational retrospective, FranceHospitalized106Patients who underwent CT including the chest for either suspicion or follow-up of COVID-19Patients aged 63.3±17.31 y, 34% female, 30% admitted to the ICU, 39.6% on thromboprophylaxis at admission, 6.6% in therapeutic anticoagulation at admissionNot reported
      Li et al,
      • Li X.
      • Xu S.
      • Yu M.
      • et al.
      Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.
      2020
      Observational retrospective, ChinaHospitalized548Patients with severe and nonsevere COVID-19Patients aged 60±15.55 y, 49% female, 49.1% severe, 2.9% in therapeutic anticoagulation at admission16.5%
      Liu et al,
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      2020
      Observational retrospective, ChinaHospitalized383Patients with COVID-19 with or without thrombocytopeniaPatients aged 46±4.5 y, 58% female12.8%
      Llitjos et al,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      2020
      Observational retrospective, FranceICU26Patients with severe COVID-19 treated with prophylactic and therapeutic anticoagulationPatients aged 68±17 y, 23% female, 31% on prophylactic anticoagulation, 69% on therapeutic anticoagulation12%
      Lodigiani et al,
      • Lodigiani C.
      • Iapichino G.
      • Carenzo L.
      • et al.
      Humanitas COVID-19 Task Force
      Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
      2020
      Observational retrospective, ItalyHospitalized388Patients with COVID-19Patients aged 66±14.81 y, 32% female, 16% admitted to the ICU26%
      Fogarty et al,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      2020
      Observational retrospective, Northern IrelandICU83Patients with COVID-19Patients aged 62±16.3 y, 34% female, 27.7% admitted to the ICU, 5% in therapeutic anticoagulation at admission15.7%
      Panigada et al,
      • Li X.
      • Xu S.
      • Yu M.
      • et al.
      Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.
      2020
      Observational retrospective, ItalyICU24Patients with COVID-19Patients aged 56±8 yNot reported
      Paranjpe et al,
      • Paranjpe I.
      • Fuster V.
      • Lala A.
      • et al.
      Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19 [letter].
      2020
      Observational retrospective comparative (anticoagulation vs no anticoagu-lation), United StatesHospitalized2773Patients with COVID-19Not reported22.7%
      Poissy et al,
      • Poissy J.
      • Goutay J.
      • Caplan M.
      • et al.
      Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence [letter].
      2020
      Observational retrospective, FranceICU107Patients with COVID-19Not reportedNot reported
      Sun et al,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      2020
      Observational retrospective, ChinaHospitalized150Patients with COVID-19Patients aged 45±16 y, 55% female2%
      Tang et al,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      2020
      Observational retrospective, ChinaHospitalized183Patients with COVID-19Patients aged 54.1±16.2 y, 46% female11.5%
      Tang et al,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      2020
      Observational retrospective, ChinaICU73Patients with COVID-19Patients aged 67±11.1 y, 38% female, 100% severe28.8%
      Tang et al,
      • Tang N.
      • Bai H.
      • Chen X.
      • Gong J.
      • Li D.
      • Sun Z.
      Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
      2020
      Observational retrospective, ChinaHospitalized449Patients with severe COVID-19Patients aged 65.1±12 y, 40% female, 100% severe, 22% received anticoagulation29.8%
      Wan et al,
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      2020
      Observational retrospective, ChinaHospitalized230Patients with COVID-19 with enteric involvementPatients aged 47.5±13.83 y, 44% female, 26.5% severe, 15% admitted to the ICU2.6%
      Wan et al,
      • Wan S.
      • Yi Q.
      • Fan S.
      • et al.
      Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients.
      2020
      Observational retrospective, ChinaHospitalized123Patients with COVID-19Patients aged 46.16±15.15 y, 46% female, 17.07% severe3.3%
      Wan et al,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      2020
      Observational retrospective, ChinaHospitalized135Patients with severe and nonsevere COVID-19Patients aged 47±3.1 y, 47% female, 29.6% severe0.1%
      Wang et al,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      2020
      Observational retrospective, ChinaHospitalized125Patients with critical and noncritical COVID-19Patients aged 41.5±15.09 y, 43% female, 20% critical, 15.2% admitted to ICU0%
      Wang et al,
      • Wang K.
      • Zhang Z.
      • Yu M.
      • Tao Y.
      • Xie M.
      15-Day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study [letter].
      2020
      Observational prospective, ChinaHospitalized548Patients with COVID-19Patients aged 59.3±4.63 y, 49% female, 23.2% critical14.2%
      Wang et al,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      2020
      Observational retrospective, ChinaICU344Severely or critically ill patients with COVID-19Patients aged 64±3.3 y, 48% female36.7%
      Wu et al,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      2020
      Observational retrospective, ChinaHospitalized280Patients with nonsevere, severe, and critical COVID-19Patients aged 43.12±19.02 y, 46% female, 26.8% severe, 2.9% critical, 2.7% admitted to ICU0%
      Xu et al,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      2020
      Observational retrospective, ChinaHospitalized187Patients with nonsevere, severe, and critical COVID-19Patients aged 62±16.67 y, 45% female, 24.1% severe, 33.2% critical, 33.2% admitted to ICU14.9%
      Yan et al,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      2020
      Observational retrospective, ChinaHospitalized193Patients with severe COVID-19 and diabetesPatients aged 64±17.77 y, 41% female, 47.7% admitted to ICU56%
      Yang et al,
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      2020
      Observational retrospective, ChinaHospitalized1476Patients with COVID-19Patients aged 57±3.3 y, 47% female16.1%
      Yang et al,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      2020
      Observational retrospective, ChinaHospitalized149Patients with COVID-19Patients aged 45.1±13.35 y, 46% female,0%
      Yao et al,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      2020
      Observational retrospective, ChinaHospitalized109Patients with severe and nonsevere COVID-19Patients aged 52±3.5 y, 60% female, 23.1% severe, 15.74% admitted to ICU11.1%
      Yin et al,
      • Yin S.
      • Huang M.
      • Li D.
      • Tang N.
      Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 [published online ahead of print April 3, 2020].
      2020
      Observational retrospective, ChinaHospitalized449Patients with severe COVID-19Patients aged 65.1±12 y, 40% female29.8%
      Peng et al,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      2020
      Observational retrospective, ChinaHospitalized112Patients with COVID-19 and cardiovascular diseasePatients aged 62±8.88 y, 53% female, 14.3% admitted to ICU15.2%
      Zhang et al,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      2020
      Observational retrospective, ChinaHospitalized221Patients with severe and nonsevere COVID-19Patients aged 55±4.5 y, 51% female, 24.9% severe, 19.9 % admitted to ICU5.4%
      Zhang et al,
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      2020
      Observational retrospective, ChinaHospitalized343Patients with COVID-19Patients aged 62±15.5 y, 51% female, 1.2% had atrial fibrillation3.8%
      Zhou et al,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      2020
      Observational retrospective, ChinaHospitalized191Patients with COVID-19Patients aged 56±15.6 y, 38% female, 26.2% admitted to the ICU16.2%
      a COVID-19 = coronavirus disease 2019; CT = computed tomography; ICU = intensive care unit.
      b Continuous variables (eg, age) were summarized as mean ± SD.

       Laboratory Findings

      Eight laboratory parameters were described by at least one study with sufficient detail to calculate means and 95% CIs (Table 2). The reported frequency of abnormal coagulation parameters was as follows: elevated D-dimer, 42%; coagulopathy (prolongation of either prothrombin time [PT] or activated thromboplastin time [aPTT]), 28%; thrombocytopenia, 20%; prolonged aPTT, 11%; and prolonged PT, 7%.
      Table 2Laboratory Findings
      aPTT = activated partial thromboplastin time; PT = prothrombin time.
      ,
      Heterogeneity was assessed using the I2 value, defining low heterogeneity as I2 <50%, moderate heterogeneity as I2 50%-75%, and high heterogeneity as I2 >75%. We used the open-source R Project software for all statistical computing.
      ,
      SI conversion factors: To convert D-dimer values to nmol/L, multiply by 5.476.
      Laboratory findingsFrequencyOverallPatients with mild and/or moderate diseasePatients with severe and/or critical diseaseSurvivorsNonsurvivors
      PT (s)

      Reference value: 10-12 s
      Prolonged PT in 7% (95% CI, 1%-14%)

      5 Studies,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      639 patients, high heterogeneity
      Mean: 12.97 (95% CI, 12.41-13.54)

      16 Studies,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Yin S.
      • Huang M.
      • Li D.
      • Tang N.
      Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 [published online ahead of print April 3, 2020].
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      high heterogeneity
      Mean: 12.51 (95% CI, 11.79-13.24)

      6 Studies,
      Centers for Disease Control and Prevention
      The Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET).
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 13.27 (95% CI, 12.57-13.97)

      8 Studies,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 13.22 (95% CI, 12.64-13.80)

      4 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      high heterogeneity
      Mean: 14.32 (95% CI, 13.02-15.61)

      4 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      high heterogeneity
      aPTT (s)

      Reference value: 22-36 s
      Prolonged aPTT in 11% (95% CI, 0% to 34%)

      3 Studies,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      298 patients, high heterogeneity
      Mean: 34.43 (95% CI, 32.06-36.8)

      13 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      ,
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      high heterogeneity
      Mean: 35.69 (95% CI, 32.74-38.64)

      6 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 36.94 (95% CI, 34.70-39.19)

      7 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      , high heterogeneity
      Mean: 36.26 (95% CI, 26.56-45.96)

      2 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      high heterogeneity
      Mean: 37.60 (95% CI, 26.56-45.96)

      2 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      high heterogeneity
      Fibrinogen (g/L)

      Reference value: 2-4 g/L
      Not reportedMean: 5.29 (95% CI, 4.76-5.81)

      9 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      ,
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      ,
      • Paranjpe I.
      • Fuster V.
      • Lala A.
      • et al.
      Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19 [letter].
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      high heterogeneity
      Mean: 4.55 (95% CI, 4.51-4.59)

      1 Study
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      Mean 6.29 (95% CI, 4.58-7.99)

      4 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      high heterogeneity
      Mean: 4.51 (95% CI, 4.47-4.55)

      2 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      low heterogeneity
      Mean: 5.30 (95% CI, 4.90-5.71)

      2 Studies,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      low heterogeneity
      D-dimer (μg/mL)

      Reference value: <0.5 μg/mL
      Elevated D-dimer in 42% (95% CI, 28%-55%)

      13 Studies,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      • Chen R.
      • Liang W.
      • Jiang M.
      • et al.
      Medical Treatment Expert Group for COVID-19. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China.
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      ,
      • Li X.
      • Xu S.
      • Yu M.
      • et al.
      Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.
      ,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      • Wang K.
      • Zhang Z.
      • Yu M.
      • Tao Y.
      • Xie M.
      15-Day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study [letter].
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      3454 patients, high heterogeneity
      Mean: 0.56 (95% CI, 0.49-0.63)

      26 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Léonard-Lorant I.
      • Delabranche X.
      • Séverac F.
      • et al.
      Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      • Lodigiani C.
      • Iapichino G.
      • Carenzo L.
      • et al.
      Humanitas COVID-19 Task Force
      Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      • Yin S.
      • Huang M.
      • Li D.
      • Tang N.
      Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 [published online ahead of print April 3, 2020].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      ,
      • Zhang L.
      • Yan X.
      • Fan Q.
      • et al.
      D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.
      high heterogeneity
      Mean: 0.48 (95% CI, 0.24-0.72)

      7 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 1.29 (95% CI, 0.72-1.86)

      13 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 0.70 (95% CI, 0.53-0.88)

      7 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Lodigiani C.
      • Iapichino G.
      • Carenzo L.
      • et al.
      Humanitas COVID-19 Task Force
      Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      high heterogeneity
      Mean: 1.10 (95% CI, 0.50-1.69) 8

      Studies,
      • Klok F.A.
      • Kruip M.J.H.A.
      • van der Meer N.J.M.
      • et al.
      Incidence of thrombotic complications in critically ill ICU patients with COVID-19.
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Lodigiani C.
      • Iapichino G.
      • Carenzo L.
      • et al.
      Humanitas COVID-19 Task Force
      Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      high heterogeneity
      Antithrombin activity (%)

      Reference value: 80%-140%
      Not reportedMean: 91 (95% CI, 90.7-91.3)

      1 Study
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      Not reportedNot reportedMean: 91 (95% CI, 90.7-91.3)

      1 Study
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      Mean: 84 (95% CI, 82.-85.3)

      1 Study
      • Tang N.
      • Li D.
      • Wang X.
      • Sun Z.
      Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
      Platelets (×109/L)

      Reference value: 150-400 × 109/L
      Thrombocytopenia in 20% (95% CI, 9%-33%)

      10 Studies,
      • Chen R.
      • Liang W.
      • Jiang M.
      • et al.
      Medical Treatment Expert Group for COVID-19. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China.
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Li X.
      • Xu S.
      • Yu M.
      • et al.
      Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Wan S.
      • Yi Q.
      • Fan S.
      • et al.
      Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang K.
      • Zhang Z.
      • Yu M.
      • Tao Y.
      • Xie M.
      15-Day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study [letter].
      ,
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      4894 patients, high heterogeneity
      Mean: 186.20 (95% CI, 161.22-211.18)

      19 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Yin S.
      • Huang M.
      • Li D.
      • Tang N.
      Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 [published online ahead of print April 3, 2020].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      high heterogeneity
      Mean: 184.70 (95% CI, 172.84-196.56)

      6 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      moderate heterogeneity
      Mean: 177.30 (95% CI, 141.93-212.67)

      13 Studies,
      • Beun R.
      • Kusadasi N.
      • Sikma M.
      • Westerink J.
      • Huisman A.
      Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2 [letter].
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Llitjos J.-F.
      • Leclerc M.
      • Chochois C.
      • et al.
      High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
      ,
      • Panigada M.
      • Bottino N.
      • Tagliabue P.
      • et al.
      Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 205.82 (95% CI, 190.37-221.27)

      5 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      low heterogeneity
      Mean: 146.71 (95% CI, 113.07-180.35)

      5 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Fogarty H.
      • Townsend L.
      • Ni Cheallaigh C.
      • et al.
      COVID19 coagulopathy in Caucasian patients.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Yang X.
      • Yang Q.
      • Wang Y.
      • et al.
      Thrombocytopenia and its association with mortality in patients with COVID-19.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      high heterogeneity
      Lymphocytes (×109/L)

      Reference value: 1.1-3.2 ×109/L
      Not reportedMean: 1.14 (95% CI, 1.04-1.25)

      19 Studies,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      ,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yang W.
      • Cao Q.
      • Qin L.
      • et al.
      Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      high heterogeneity
      Mean: 1.21 (95% CI, 1.07-1.34)

      8 Studies,
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      ,
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 0.79 (95% CI, 0.69-0.89)

      11 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      ,
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Peng Y.D.
      • Meng K.
      • Guan H.Q.
      • et al.
      Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese].
      ,
      • Zhang G.
      • Hu C.
      • Luo L.
      • et al.
      Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China.
      high heterogeneity
      Mean: 0.92 (95% CI, 0.81-1.04)

      5 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      high heterogeneity
      Mean: 0.62 (95% CI, 0.55-0.70)

      6 Studies,
      • Cao J.
      • Tu W.-J.
      • Cheng W.
      • et al.
      Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China.
      ,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      ,
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      ,
      • Yao Q.
      • Wang P.
      • Wang X.
      • et al.
      A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.
      ,
      • Zhou F.
      • Yu T.
      • Du R.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020;395(10229):1038].
      moderate heterogeneity
      Neutrophils (×109/L)

      Reference value: 3.8-9.5 × 109/L
      Not reportedMean: 3.59 (95% CI, 2.91-4.27)

      17 Studies,
      • Chen T.
      • Dai Z.
      • Mo P.
      • et al.
      Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study [published online ahead of print April April 11, 2020].
      • Gong J.
      • Ou J.
      • Qiu X.
      • et al.
      A tool to early predict severe corona virus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China.
      • He R.
      • Lu Z.
      • Zhang L.
      • et al.
      The clinical course and its correlated immune status in COVID-19 pneumonia.
      ,
      • Liu Y.
      • Sun W.
      • Guo Y.
      • et al.
      Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study.
      ,
      • Sun C.
      • Zhang X.B.
      • Dai Y.
      • Xu X.Z.
      • Zhao J.
      Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province [in Chinese].
      ,
      • Tang X.
      • Du R.-H.
      • Wang R.
      • et al.
      Comparison of hospitalized patients with ARDS caused by COVID-19 and H1N1.
      ,
      • Wan Y.
      • Li J.
      • Shen L.
      • et al.
      Enteric involvement in hospitalised patients with COVID-19 outside Wuhan [letter].
      ,
      • Wan S.
      • Xiang Y.
      • Fang W.
      • et al.
      Clinical features and treatment of COVID-19 patients in northeast Chongqing.
      ,
      • Wang R.
      • Pan M.
      • Zhang X.
      • et al.
      Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China.
      ,
      • Wang Y.
      • Lu X.
      • Li Y.
      • et al.
      Clinical course and outcomes of 344 intensive care patients with COVID-19.
      • Wu J.
      • Li W.
      • Shi X.
      • et al.
      Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).
      • Xu B.
      • Fan C.-Y.
      • Wang A.-L.
      • et al.
      Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China.
      • Yan Y.
      • Yang Y.
      • Wang F.
      • et al.
      Clinical characteristics and outcomes of patients with severe covid-19 with diabetes.