Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination.

Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group ≥70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to ≥60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001). The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.

Krzywicka K ，van de Munckhof A ，Sánchez van Kammen M ，Heldner MR ，Jood K ，Lindgren E ，Tatlisumak T ，Putaala J ，Kremer Hovinga JA ，Middeldorp S ，Levi MM ，Cordonnier C ，Arnold M ，Zwinderman AH ，Ferro JM ，Coutinho JM ，Aguiar de Sousa D ... -  《-》

Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency.

Cerebral venous sinus thrombosis (CVST) has been described after vaccination against SARS-CoV-2. The clinical characteristics of 213 post-vaccination CVST cases notified to the European Medicines Agency are reported. Data on adverse drug reactions after SARS-CoV-2 vaccination notified until 8 April 2021 under the Medical Dictionary for Regulatory Activities Term 'Central nervous system vascular disorders' were obtained from the EudraVigilance database. Post-vaccination CVST was compared with 100 European patients with CVST from before the COVID-19 pandemic derived from the International CVST Consortium. In all, 213 CVST cases were identified: 187 after AstraZeneca/Oxford (ChAdOx1 nCov-19) vaccination and 26 after a messenger RNA (mRNA) vaccination (25 with Pfizer/BioNTech, BNT162b2, and one with Moderna, mRNA-1273). Thrombocytopenia was reported in 107/187 CVST cases (57%, 95% confidence interval [CI] 50%-64%) in the ChAdOx1 nCov-19 group, in none in the mRNA vaccine group (0%, 95% CI 0%-13%) and in 7/100 (7%, 95% CI 3%-14%) in the pre-COVID-19 group. In the ChAdOx1 nCov-19 group, 39 (21%) reported COVID-19 polymerase chain reaction tests were performed within 30 days of CVST symptom onset, and all were negative. Of the 117 patients with a reported outcome in the ChAdOx1 nCov-19 group, 44 (38%, 95% CI 29%-47%) had died, compared to 2/10 (20%, 95% CI 6%-51%) in the mRNA vaccine group and 3/100 (3%, 95% CI 1%-8%) in the pre-COVID-19 group. Mortality amongst patients with thrombocytopenia in the ChAdOx1 nCov-19 group was 49% (95% CI 39%-60%). Cerebral venous sinus thrombosis occurring after ChAdOx1 nCov-19 vaccination has a clinical profile distinct from CVST unrelated to vaccination. Only CVST after ChAdOx1 nCov-19 vaccination was associated with thrombocytopenia.

Krzywicka K ，Heldner MR ，Sánchez van Kammen M ，van Haaps T ，Hiltunen S ，Silvis SM ，Levi M ，Kremer Hovinga JA ，Jood K ，Lindgren E ，Tatlisumak T ，Putaala J ，Aguiar de Sousa D ，Middeldorp S ，Arnold M ，Coutinho JM ，Ferro JM ... -  《-》

Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.

To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS). 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study. The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events. The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test. Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.

Hippisley-Cox J ，Patone M ，Mei XW ，Saatci D ，Dixon S ，Khunti K ，Zaccardi F ，Watkinson P ，Shankar-Hari M ，Doidge J ，Harrison DA ，Griffin SJ ，Sheikh A ，Coupland CAC ... -  《BMJ-British Medical Journal》

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Sánchez van Kammen M ，Aguiar de Sousa D ，Poli S ，Cordonnier C ，Heldner MR ，van de Munckhof A ，Krzywicka K ，van Haaps T ，Ciccone A ，Middeldorp S ，Levi MM ，Kremer Hovinga JA ，Silvis S ，Hiltunen S ，Mansour M ，Arauz A ，Barboza MA ，Field TS ，Tsivgoulis G ，Nagel S ，Lindgren E ，Tatlisumak T ，Jood K ，Putaala J ，Ferro JM ，Arnold M ，Coutinho JM ，Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group ，Sharma AR ，Elkady A ，Negro A ，Günther A ，Gutschalk A ，Schönenberger S ，Buture A ，Murphy S ，Paiva Nunes A ，Tiede A ，Puthuppallil Philip A ，Mengel A ，Medina A ，Hellström Vogel Å ，Tawa A ，Aujayeb A ，Casolla B ，Buck B ，Zanferrari C ，Garcia-Esperon C ，Vayne C ，Legault C ，Pfrepper C ，Tracol C ，Soriano C ，Guisado-Alonso D ，Bougon D ，Zimatore DS ，Michalski D ，Blacquiere D ，Johansson E ，Cuadrado-Godia E ，De Maistre E ，Carrera E ，Vuillier F ，Bonneville F ，Giammello F ，Bode FJ ，Zimmerman J ，d'Onofrio F ，Grillo F ，Cotton F ，Caparros F ，Puy L ，Maier F ，Gulli G ，Frisullo G ，Polkinghorne G ，Franchineau G ，Cangür H ，Katzberg H ，Sibon I ，Baharoglu I ，Brar J ，Payen JF ，Burrow J ，Fernandes J ，Schouten J ，Althaus K ，Garambois K ，Derex L ，Humbertjean L ，Lebrato Hernandez L ，Kellermair L ，Morin Martin M ，Petruzzellis M ，Cotelli M ，Dubois MC ，Carvalho M ，Wittstock M ，Miranda M ，Skjelland M ，Bandettini di Poggio M ，Scholz MJ ，Raposo N ，Kahnis R ，Kruyt N ，Huet O ，Sharma P ，Candelaresi P ，Reiner P ，Vieira R ，Acampora R ，Kern R ，Leker R ，Coutts S ，Bal S ，Sharma SS ，Susen S ，Cox T ，Geeraerts T ，Gattringer T ，Bartsch T ，Kleinig TJ ，Dizonno V ，Arslan Y ... -  《-》

First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.

Kerr S ，Joy M ，Torabi F ，Bedston S ，Akbari A ，Agrawal U ，Beggs J ，Bradley D ，Chuter A ，Docherty AB ，Ford D ，Hobbs R ，Katikireddi SV ，Lowthian E ，de Lusignan S ，Lyons R ，Marple J ，McCowan C ，McGagh D ，McMenamin J ，Moore E ，Murray JK ，Owen RK ，Pan J ，Ritchie L ，Shah SA ，Shi T ，Stock S ，Tsang RSM ，Vasileiou E ，Woolhouse M ，Simpson CR ，Robertson C ，Sheikh A ... -  《-》