key: cord-0805627-bmxjttsg
authors: Kunutsor, Setor K.; Laukkanen, Jari A.
title: Incidence of venous and arterial thromboembolic complications in COVID-19: A systematic review and meta-analysis
date: 2020-08-11
journal: Thromb Res
DOI: 10.1016/j.thromres.2020.08.022
sha: 9a8e6a9a1fcc261a3fdfd414292f96d6f8306229
doc_id: 805627
cord_uid: bmxjttsg

nan

Arterial thrombotic disease (atherosclerotic cardiovascular disease, CVD) and venous thromboembolism (VTE) (comprising of deep vein thrombosis (DVT) and pulmonary embolism (PE)), two distinct but closely related diseases, [1] constitute major public health problems and are associated with substantial morbidity, premature mortality, and high economic costs. The coronavirus disease 2019 (COVID-19) pandemic which is one of the most significant modern-day public health challenges, predominantly affects the respiratory system, causing severe pneumonia and respiratory distress syndrome. Emerging data suggests COVID-19 adversely affects multiple organs;

gastrointestinal, liver, kidney, neurological and cardiac complications have been reported. [2] [3] [4] Apart from pre-existing comorbidities such as CVD, hypertension, chronic kidney disease, chronic liver disease and diabetes being linked to increased risk of severe illness or death; [5] some extrapulmonary complications of COVID-19 such as acute myocardial injury have been shown to be associated with fatal outcomes. [6] Recently, COVID-19 has been linked to venous and arterial thromboembolic disease (henceforth referred to as thromboembolic complications). Three recent most downloaded and key studies published in the journal reported a high incidence of thromboembolic complications in COVID-19 patients, particularly in those admitted to the intensive care unit (ICU). [7] [8] [9] Given the sparseness of the data and evolving nature of the disease, the thromboembolic complications of COVID-19 and their incidence is not clearly defined. There is a need for robust aggregation of data on thromboembolic complications of COVID-19, which will be of great value for policy makers, healthcare providers and clinicians to aid decision making and implementing more efficacious preventative strategies. In this context, we conducted a systematic review and meta-analysis to attempt to address the following questions: For PE subtypes, the incidence was 9.1% (5.0-14.3) for segmental PE, 7.5% (0.5-19.9) for central/lobar PE, 6.3% (2.3-11.8) for subsegmental PE, 4.1% (2.0-6.9) for main pulmonary artery PE and 1.9% (0.0-6.5) for multiple segmental PE (Supplementary Material 7) .

Other thromboembolic complications are reported in Figure 1B thrombosis, but these were based on single reports (Figure 1B) .

The incidence of thromboembolic complications in patients with severe COVID-19 are reported in Supplementary Materials 8-11 . The pooled incidence for VTE, PE and DVT was 21.6% (14.3-29.8), 11.8% (6.4-18.5) and 18.2% (9.6-28.6) respectively (Supplementary Material 8) . The incidence of distal, proximal and upper extremity DVT was 21.5% (0.0-72.8), 7.8% (1.8-16.9) and 3.5% (1.2-6.9) respectively (Supplementary Material 9) . For PE subtypes, the incidence was 7.7% Based on the most up-to-date published evidence on patients with COVID-19, there is a high incidence of thromboembolic complications in these patients (ranging from 7.2 to 40.8%), which appears to be driven by venous thromboembolic disease. These thromboembolic complications are remarkably high in COVID-19 infection despite the use of thromboprophylaxis in patients. The most frequently diagnosed venous thromboembolic complication in the overall population is PE, with segmental and central/lobar PE being more common than other subtypes. Furthermore, it appears the incidence of thromboembolic complications is substantially higher in severe COVID-19 disease compared to the overall population, with a higher incidence of DVT than PE. Though arterial thrombosis and VTE have historically been viewed as two distinct diseases with different pathophysiology, they appear to be closely related via some shared risk factors (obesity and smoking) and mechanistic pathways (such as coagulation, platelet activation and dyslipidaemia). [1] Though the mechanistic pathways are still not very clear, the predisposition to venous and arterial thromboembolism by COVID-19 especially in severe infection has been attributed to the overwhelming inflammatory response, hypoxia, DIC and immobilisation. [2] There is an on-going J o u r n a l P r e -p r o o f Journal Pre-proof discussion that pulmonary thrombotic events in COVID-19 may not be due to emboli but rather as a result of in-situ pulmonary thrombosis. [10] The high incidence of thromboembolic complications in COVID-19 patients is a big source of concern, especially given the fact that systemic thromboprophylactic agents were administered to patients. Furthermore, it has been acknowledged by some studies that the thromboembolic incidence estimates reported are actually underestimates. [7, 8] Aggressive monitoring of markers of thromboembolic complications such as D-dimer during admission, use of sensitive and specific VTE diagnostic tools and effective pharmacological thromboprophylaxis may be required in the management of patients with COVID-19. Given the bleeding risks associated with anticoagulants, clinical decisions to initiate thromboprophylaxis should also be individualised and tailored to each patient.

There were some limitations in this study, but these were all inherent. These included the low methodological quality of some of the studies and small sample sizes; however, this was not unexpected given the urgency to understand the clinical course of COVID-19. Other limitations included some findings being based on single reports and the fact that some of the incidence data were under-reported due to inability to perform diagnostic imaging tests in all patients due to strict isolation procedures.

Aggregate analysis of the available literature suggests a high incidence of thromboembolic complications in patients hospitalised with COVID-19, particularly in those with severe disease. The incidence is higher for venous thromboembolic events compared to arterial thromboembolic complications. There is an urgent need for improved diagnostic strategies as well as determining the most effective thromboprophylactic agents and their optimal dosages to be used in these patients. 

Arterial and venous thrombosis: What's the link? A narrative review

Cardiovascular complications in COVID-19: A systematic review and meta-analysis

Hepatic manifestations and complications of COVID-19: A systematic review and meta-analysis

Extrapulmonary manifestations of COVID-19: Radiologic and clinical overview

Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis

Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom

Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in

Thrombosis risk associated with COVID-19 infection. A scoping review