Association of cerebral venous thrombosis with recent COVID-19 vaccination: case-crossover study using ascertainment through neuroimaging in Scotland

Abstract Background To investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland. Methods Case-crossover study comparing cases of CVT recently exposed to vaccination (1–14 days after vaccination) with cases less recently exposed. Cases in Scotland from 1 December 2020 were ascertained through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021, linked to national vaccination records. The main outcome measure was primary acute CVT. Results Of 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). Conclusions These findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear.

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Association of cerebral venous thrombosis with recent COVID-19 vaccination: case-crossover study using ascertainment through neuroimaging in Scotland

10.1101/2021.08.23.21261779 ◽

2021 ◽

Author(s):

Paul M McKeigue ◽

Raj Burgul ◽

Jen Bishop ◽

Chris Robertson ◽

Jim McMenamin ◽

...

Keyword(s):

Venous Thrombosis ◽

Crossover Study ◽

Cerebral Venous Thrombosis ◽

Rate Ratio ◽

Credible Interval ◽

Yellow Card ◽

Hospital Discharges ◽

Recent Exposure ◽

Case Crossover ◽

The Uk

AbstractObjectivesTo investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland.DesignCase-crossover study comparing recent (1-14 days after vaccination) with less recent exposure to vaccination among cases of CVT.SettingNational data for Scotland from 1 December 2020, with diagnosed CVT case ascertainment through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021 and with linkage to vaccination records.Main outcome measurePrimary acute cerebral venous thrombosisResultsOf 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). The 95% credible interval for the rate ratio associated with recent versus less recent exposure to BNT162b2 (0.6 to 95.8) was too wide for useful inference.ConclusionsThese findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear.What is already known on this topicThe risk of cerebral venous thrombosis (CVT) within 28 days of receiving the AstraZeneca ChAdOx1 vaccine has been estimated as 18 to 25 per million doses in Germany and Scandinavia, but only 5 per million doses in the UK based on the Yellow Card reporting scheme. Risk estimates based on adverse event reporting systems are subject to under-ascertainment and other biases.What this study addsAll diagnosed cases of CVT in Scotland were ascertained by searching neuroimaging studies from December 2020 to May 2021 and linked to national vaccination records. The risk of CVT within 28 days of vaccination with ChAdOx1 was estimated as 3.5 per million doses with an upper bound of 6 per million doses, against a background incidence of about 12 per million adults per year. This indicates that the Yellow Card system has not seriously underestimated the risk in the UK; the explanation for higher risk in other European countries is not clear.

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Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis

The Journal of Headache and Pain ◽

10.1186/s10194-021-01324-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

David García-Azorín ◽

Thien Phu Do ◽

Andreas R. Gantenbein ◽

Jakob Møller Hansen ◽

Marcio Nattan P. Souza ◽

...

Keyword(s):

Venous Thrombosis ◽

Intracranial Hemorrhage ◽

Cerebral Venous Thrombosis ◽

Adenovirus Vector ◽

Multiple Organ ◽

Post Vaccination ◽

Headache Onset ◽

Red Flag ◽

Probability Of Death ◽

New Onset

Abstract Background Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients. Findings We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage. We identified 77 cases of CVT after COVID-19 vaccination. Patients’ age was below 60 years in 74/77 (95.8%) cases and 61/68 (89.7%) were women. Headache was described in 38/77 (49.4%) cases, and in 35/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19/77 (24.7%) cases, intracranial hemorrhage in 33/77 (42.9%) cases and 19/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0–9.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7–20.8, p < 0.001), but not with death (OR: 0.51, 95% CI: 0.18–1.47, p = 0.213). Conclusion Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.

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