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

Baldini, Tommaso; Asioli, Gian Maria; Romoli, Michele; Carvalho Dias, Mariana; Schulte, Eva C.; Hauer, Larissa; Aguiar De Sousa, Diana; Sellner, Johann; Zini, Andrea

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.