Background The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. Methods In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. Results We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction Conclusions Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

https://thorax.bmj.com/content/thoraxjnl/early/2021/03/24/thoraxjnl-2020-215383.full.pdf

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis.

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

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Patients with COVID-19: in the dark-NETs of neutrophils.

Background and purpose Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease-2019 (COVID-19). Methods We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID-19-associated CVT. The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO-CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were evaluated for bias using the Newcastle-Ottawa scale. A proportion meta-analysis was performed to estimate the frequency of CVT among hospitalized COVID-19 patients. Results We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS-CoV-2 infection were present in 31%. In-hospital mortality was 40%. Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS-CoV-2 infection was 0.08% (95% confidence interval [CI]: 0.01-0.5). In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID-19 (cohort of 406 patients, 95% CI: 1.47-11.39). Conclusions Cerebral venous thrombosis in the context of SARS-CoV-2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, because the diagnosis of this potentially life-threatening condition in COVID-19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID-19-associated CVT.

Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis.

OBJECTIVE: Emerging data indicates an increased risk for cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and highlights the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke We conducteda systematic review and meta-analysis to evaluate the aforementioned considerations METHODS: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status We used a random-effects model Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (95%CI) RESULTS: We identified 18 cohort studies including 67,845 patients Among patients with SARS-CoV-2, 1 3% (95%CI:0 9-1 6%;I(2) =87%) were hospitalized for cerebrovascular events, 1 1% (95%CI:0 8-1 3%;I(2) =85%) for ischemic stroke, and 0 2% (95%CI:0 1-0 3%;I(2) =64%) for hemorrhagic stroke Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR=3 58,95%CI:1 43-8 92;I(2) =43%) and cryptogenic stroke (OR=3 98,95%CI:1 62-9 77;I(2) =0%) Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls (OR=1 39, 95%CI:1 04-1 86;I(2) =0%) SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR=1 42,95%CI:0 65-3 10;I(2) =0%) or endovascular thrombectomy (OR=0 78,95%CI:0 35-1 74;I(2) =0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic Odds for in-hospital mortality were higher among SARS-CoV-2stroke patients compared to non-infected contemporary or historical stroke patients (OR=5 60,95%CI:3 19-9 80;I(2) =45%) INTERPRETATION: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular It may also be related to an increased mortality risk This article is protected by copyright All rights reserved

The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-analysis

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as 'red flags' to alarm clinicians in recognizing COVID-19-related stroke.

https://journals.sagepub.com/doi/pdf/10.1177/1756286420978004

Saeideh Neshin Aghayari Sheikh

Papers

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.