High Incidence and Unique Features of Cerebral Venous Sinus Thrombosis in Hospitalized Patients With COVID-19 Infection

Margy E. McCullough-Hicks, MD; Daniel J. Halterman, MS; David Anderson, BSAE; Kenneth Cohen, MD; Kamakshi Lakshminarayan, MBBS, PhD

Disclosures

Stroke. 2022;53(9):e407-e410. 

In This Article

Abstract and Introduction

Abstract

Background: Cerebral venous sinus thrombosis (CVST) secondary to vaccine-induced thrombotic thrombocytopenia is an extremely rare side effect of adenovirus-based COVID-19 vaccines. CVST incidence associated with COVID-19 itself has not been widely reported. We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic.

Methods: We analyzed de-identified electronic medical records of a retrospective cohort of patients admitted with COVID-19 to >200 hospitals between March 2020 and March 2021. We used International Classification of Diseases, Tenth Revision codes and natural language processing extracts to identify patients with a new CVST diagnosis during COVID-19 hospitalization. The primary outcome was CVST incidence in hospitalized, COVID-19-positive patients. Secondary outcomes included CVST incidence and mortality. Incidence rates were calculated using the DerSimonian-Laird estimator method.

Results: Ninety-one thousand seven hundred twenty-seven patients were evaluated; 22 had new CVST diagnoses by electronic medical record review. CVST incidence in the hospitalized COVID-19 cohort was 231 per 1 000 000 person-years (95% CI, 152.1–350.8). Females<50 had the highest incidence overall (males <50: 378.4 [142–1008.2]; females<50: 796.5 [428.6–1480.4]). In patients ≥50 years old, males had a higher estimated CVST incidence (males≥50: 130.5 [54.3–313.6]; females≥50: 88.8 [28.6–275.2]). Older patients (45.5% of patients ≥50 versus 0% of <50 years of age, P=0.012) and males (44.4% of males versus 7.7% of females, P=0.023) were more likely to die in hospital.

Conclusions: CVST incidence in COVID-19–positive hospitalized patients is high. Advanced age and male gender were associated with likelihood of death in hospital; further studies are required to confirm these findings.

Graphic Abstract: A graphic abstract is available for this article.

Introduction

COVID-19 is a primary respiratory disease. However, arterial and venous thrombosis influence the morbidity and mortality of COVID-19, with 74% higher odds of mortality among patients who develop thromboembolism.[1]

Two adenovirus-based COVID-19 vaccinations have been associated with a rare risk of simultaneous acute thrombosis—usually cerebral venous sinus thrombosis (CVST)—and thrombocytopenia in an entity called vaccine-induced thrombotic thrombocytopenia.[2,3]

CVST is rare in the non-COVID general population. Risk factors for CVST include pregnancy, malignancy, hormone use, and thrombophilia.[4] In the pre-COVID US population, reported CVST incidence ranges from 13.9 and 20.2 per million[5] and is 3× more frequent in females.[6]

CVST incidence associated with adenovirus-based COVID-19 vaccination is extremely low and ranges between 7.5 per million after the AstraZeneca vaccine (99% CI, 2.7–4.7)[3] to 0.9 per million (99% CI, 0.2–2.3) after the Janssen vaccine.[7] The incidence of CVST in unvaccinated COVID-19–infected patients has not been widely reported. The 2 existing publications reporting CVST incidence in COVID-19 patients have very different reported incidence rates, between 42.8 (95% CI, 28.5–64.2)[8] and 207.1 per million hospitalized patients (99% CI, 23.3–757.7).[7]

We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic—before vaccines were widely available—and describe patient characteristics and disease course.

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