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      Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis

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          Abstract

          Background

          Studies have suggested that there is increased risk of thromboembolism (TE) associated with coronavirus disease 2019 (COVID-19). However, overall arterial and venous TE rates of COVID-19 and effect of TE on COVID-19 mortality is unknown.

          Methods

          We did a systematic review and meta-analysis of studies evaluating TE in COVID-19. We searched PubMed, Cochrane, and Embase for studies published up to June 12, 2020. Random effects models were used to produce summary TE rates and odds ratios (OR) of mortality in COVID-19 patients with TE compared to those without TE. Heterogeneity was quantified with I 2 .

          Findings

          Of 425 studies identified, 42 studies enrolling 8271 patients were included in the meta-analysis. Overall venous TE rate was 21% (95% CI:17–26%): ICU, 31% (95% CI: 23–39%). Overall deep vein thrombosis rate was 20% (95% CI: 13–28%): ICU, 28% (95% CI: 16–41%); postmortem, 35% (95% CI:15–57%). Overall pulmonary embolism rate was 13% (95% CI: 11–16%): ICU, 19% (95% CI:14–25%); postmortem, 22% (95% CI:16–28%). Overall arterial TE rate was 2% (95% CI: 1–4%): ICU, 5% (95%CI: 3–7%). Pooled mortality rate among patients with TE was 23% (95%CI:14–32%) and 13% (95% CI:6–22%) among patients without TE. The pooled odds of mortality were 74% higher among patients who developed TE compared to those who did not (OR, 1.74; 95%CI, 1.01–2.98; P = 0.04).

          Interpretation

          TE rates of COVID-19 are high and associated with higher risk of death. Robust evidence from ongoing clinical trials is needed to determine the impact of thromboprophylaxis on TE and mortality risk of COVID-19.

          Funding

          None.

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          Most cited references61

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Fei Zhou, Ting Yu, Ronghui Du … (2020)
            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

              David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2009)
              Article 0 comments Cited 7170 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): EClinicalMedicine
                Journal ID (iso-abbrev): EClinicalMedicine
                Title: EClinicalMedicine
                Publisher: The Authors. Published by Elsevier Ltd.
                ISSN (Electronic): 2589-5370
                Publication date PMC-release: 20 November 2020
                Publication date (Print): December 2020
                Publication date (Electronic): 20 November 2020
                Volume: 29
                Page: 100639
                Affiliations
                [0001]Department of Surgery, University of California San Diego Health System, San Diego, CA 92093, United States
                Author notes
                [* ]Corresponding author.
                [1]

                Contributed equally as co-first authors.

                Article
                Publisher Item ID: S2589-5370(20)30383-7 Publisher ID: 100639
                DOI: 10.1016/j.eclinm.2020.100639
                PMC ID: 7679115
                PubMed ID: 33251499
                SO-VID: 96bec67a-cc10-479b-a6e2-74f2ae126c7d
                Copyright © © 2020 The Authors
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 18 August 2020
                Date revision received : 31 October 2020
                Date accepted : 2 November 2020
                Categories
                Subject: Article

                Keywords: covid-19,venous thromboembolism,arterial thromboembolism,deep vein thrombosis,pulmonary embolism
                Data availability:
                Keywords: covid-19, venous thromboembolism, arterial thromboembolism, deep vein thrombosis, pulmonary embolism

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