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1.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1596718

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Sinus Thrombosis, Intracranial , Thrombocytopenia , Thrombosis , COVID-19/epidemiology , Female , Humans , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology
2.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1456030

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Sinus Thrombosis, Intracranial , Thrombocytopenia , Thrombosis , COVID-19/epidemiology , Female , Humans , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology
4.
Ann Neurol ; 89(2): 380-388, 2021 02.
Article in English | MEDLINE | ID: covidwho-938391

ABSTRACT

OBJECTIVE: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a 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 (CIs). RESULTS: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected 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, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I2 = 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, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I2 = 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. ANN NEUROL 2021;89:380-388.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hospital Mortality , SARS-CoV-2 , Stroke/epidemiology , Case-Control Studies , Comorbidity , Humans , Thrombectomy/statistics & numerical data , Thrombolytic Therapy/statistics & numerical data
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