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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

Steven Kerr Orcid Logo, Mark Joy Orcid Logo, Fatemeh Torabi Orcid Logo, Stuart Bedston, Ashley Akbari Orcid Logo, Utkarsh Agrawal Orcid Logo, Jillian Beggs Orcid Logo, Declan Bradley Orcid Logo, Antony Chuter Orcid Logo, Annemarie B. Docherty Orcid Logo, David Ford Orcid Logo, Richard Hobbs Orcid Logo, Srinivasa Vittal Katikireddi Orcid Logo, Emily Lowthian, Simon de Lusignan Orcid Logo, Ronan Lyons Orcid Logo, James Marple, Colin McCowan Orcid Logo, Dylan McGagh Orcid Logo, Jim McMenamin, Emily Moore Orcid Logo, Josephine-L. K. Murray Orcid Logo, Rhiannon Owen Orcid Logo, Jiafeng Pan Orcid Logo, Lewis Ritchie Orcid Logo, Syed Ahmar Shah Orcid Logo, Ting Shi Orcid Logo, Sarah Stock Orcid Logo, Ruby S. M. Tsang Orcid Logo, Eleftheria Vasileiou Orcid Logo, Mark Woolhouse Orcid Logo, Colin R. Simpson Orcid Logo, Chris Robertson Orcid Logo, Aziz Sheikh

PLOS Medicine, Volume: 19, Issue: 2, Start page: e1003927

Swansea University Authors: Fatemeh Torabi Orcid Logo, Stuart Bedston, Ashley Akbari Orcid Logo, David Ford Orcid Logo, Emily Lowthian, Ronan Lyons Orcid Logo, Rhiannon Owen Orcid Logo

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DOI (Published version): 10.1371/journal.pmed.1003927

Abstract

BackgroundSeveral countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely...

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ISSN: 1549-1676
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2022-08-16T13:22:05.1885760</datestamp><bib-version>v2</bib-version><id>60273</id><entry>2022-06-18</entry><title>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</title><swanseaauthors><author><sid>f569591e1bfb0e405b8091f99fec45d3</sid><ORCID>0000-0002-5853-4625</ORCID><firstname>Fatemeh</firstname><surname>Torabi</surname><name>Fatemeh Torabi</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>c79d07eaba5c9515c0df82b372b76a41</sid><firstname>Stuart</firstname><surname>Bedston</surname><name>Stuart Bedston</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>aa1b025ec0243f708bb5eb0a93d6fb52</sid><ORCID>0000-0003-0814-0801</ORCID><firstname>Ashley</firstname><surname>Akbari</surname><name>Ashley Akbari</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>52fc0c473b0da1b7218d87f9fc68a3e6</sid><ORCID>0000-0001-6551-721X</ORCID><firstname>David</firstname><surname>Ford</surname><name>David Ford</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>db5bc529b8a9dfca2b4a268d14e03479</sid><firstname>Emily</firstname><surname>Lowthian</surname><name>Emily Lowthian</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>83efcf2a9dfcf8b55586999d3d152ac6</sid><ORCID>0000-0001-5225-000X</ORCID><firstname>Ronan</firstname><surname>Lyons</surname><name>Ronan Lyons</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>0d30aa00eef6528f763a1e1589f703ec</sid><ORCID>0000-0001-5977-376X</ORCID><firstname>Rhiannon</firstname><surname>Owen</surname><name>Rhiannon Owen</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-06-18</date><deptcode>HDAT</deptcode><abstract>BackgroundSeveral countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.Methods and findingsWe created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.ConclusionsIn this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk&#x2013;benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.</abstract><type>Journal Article</type><journal>PLOS Medicine</journal><volume>19</volume><journalNumber>2</journalNumber><paginationStart>e1003927</paginationStart><paginationEnd/><publisher>Public Library of Science (PLoS)</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>1549-1676</issnElectronic><keywords/><publishedDay>22</publishedDay><publishedMonth>2</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-02-22</publishedDate><doi>10.1371/journal.pmed.1003927</doi><url/><notes/><college>COLLEGE NANME</college><department>Health Data Science</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>HDAT</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>MC_PC_19075/MRC_/Medical Research Council/United Kingdom; BHF_/British Heart Foundation/United Kingdom; MR/V028367/1/MRC_/Medical Research Council/United Kingdom; MC_PC_20058/MRC_/Medical Research Council/United Kingdom; MC_PC 19075/MRC_/Medical Research Council/United Kingdom; WT_/Wellcome Trust/United Kingdom</funders><projectreference/><lastEdited>2022-08-16T13:22:05.1885760</lastEdited><Created>2022-06-18T10:42:55.9056551</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Steven</firstname><surname>Kerr</surname><orcid>0000-0002-3643-7859</orcid><order>1</order></author><author><firstname>Mark</firstname><surname>Joy</surname><orcid>0000-0002-4974-3724</orcid><order>2</order></author><author><firstname>Fatemeh</firstname><surname>Torabi</surname><orcid>0000-0002-5853-4625</orcid><order>3</order></author><author><firstname>Stuart</firstname><surname>Bedston</surname><order>4</order></author><author><firstname>Ashley</firstname><surname>Akbari</surname><orcid>0000-0003-0814-0801</orcid><order>5</order></author><author><firstname>Utkarsh</firstname><surname>Agrawal</surname><orcid>0000-0001-5181-6120</orcid><order>6</order></author><author><firstname>Jillian</firstname><surname>Beggs</surname><orcid>0000-0002-7591-3256</orcid><order>7</order></author><author><firstname>Declan</firstname><surname>Bradley</surname><orcid>0000-0003-1468-1823</orcid><order>8</order></author><author><firstname>Antony</firstname><surname>Chuter</surname><orcid>0000-0002-0646-5939</orcid><order>9</order></author><author><firstname>Annemarie B.</firstname><surname>Docherty</surname><orcid>0000-0001-8277-420x</orcid><order>10</order></author><author><firstname>David</firstname><surname>Ford</surname><orcid>0000-0001-6551-721X</orcid><order>11</order></author><author><firstname>Richard</firstname><surname>Hobbs</surname><orcid>0000-0001-7976-7172</orcid><order>12</order></author><author><firstname>Srinivasa Vittal</firstname><surname>Katikireddi</surname><orcid>0000-0001-6593-9092</orcid><order>13</order></author><author><firstname>Emily</firstname><surname>Lowthian</surname><order>14</order></author><author><firstname>Simon de</firstname><surname>Lusignan</surname><orcid>0000-0002-8553-2641</orcid><order>15</order></author><author><firstname>Ronan</firstname><surname>Lyons</surname><orcid>0000-0001-5225-000X</orcid><order>16</order></author><author><firstname>James</firstname><surname>Marple</surname><order>17</order></author><author><firstname>Colin</firstname><surname>McCowan</surname><orcid>0000-0002-9466-833x</orcid><order>18</order></author><author><firstname>Dylan</firstname><surname>McGagh</surname><orcid>0000-0002-6772-2775</orcid><order>19</order></author><author><firstname>Jim</firstname><surname>McMenamin</surname><order>20</order></author><author><firstname>Emily</firstname><surname>Moore</surname><orcid>0000-0002-9634-3299</orcid><order>21</order></author><author><firstname>Josephine-L. K.</firstname><surname>Murray</surname><orcid>0000-0002-1511-7944</orcid><order>22</order></author><author><firstname>Rhiannon</firstname><surname>Owen</surname><orcid>0000-0001-5977-376X</orcid><order>23</order></author><author><firstname>Jiafeng</firstname><surname>Pan</surname><orcid>0000-0001-5993-3209</orcid><order>24</order></author><author><firstname>Lewis</firstname><surname>Ritchie</surname><orcid>0000-0002-9380-7641</orcid><order>25</order></author><author><firstname>Syed Ahmar</firstname><surname>Shah</surname><orcid>0000-0001-5672-0443</orcid><order>26</order></author><author><firstname>Ting</firstname><surname>Shi</surname><orcid>0000-0002-4101-4535</orcid><order>27</order></author><author><firstname>Sarah</firstname><surname>Stock</surname><orcid>0000-0003-4308-856x</orcid><order>28</order></author><author><firstname>Ruby S. M.</firstname><surname>Tsang</surname><orcid>0000-0002-2520-526x</orcid><order>29</order></author><author><firstname>Eleftheria</firstname><surname>Vasileiou</surname><orcid>0000-0001-6850-7578</orcid><order>30</order></author><author><firstname>Mark</firstname><surname>Woolhouse</surname><orcid>0000-0003-3765-8167</orcid><order>31</order></author><author><firstname>Colin R.</firstname><surname>Simpson</surname><orcid>0000-0002-5194-8083</orcid><order>32</order></author><author><firstname>Chris</firstname><surname>Robertson</surname><orcid>0000-0001-6848-5241</orcid><order>33</order></author><author><firstname>Aziz</firstname><surname>Sheikh</surname><order>34</order></author></authors><documents><document><filename>60273__24636__f014bedb6fc74475a98351b20e442036.pdf</filename><originalFilename>60273.pdf</originalFilename><uploaded>2022-07-19T12:36:38.3372311</uploaded><type>Output</type><contentLength>1039438</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; 2022 Kerr et al. 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spelling 2022-08-16T13:22:05.1885760 v2 60273 2022-06-18 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 f569591e1bfb0e405b8091f99fec45d3 0000-0002-5853-4625 Fatemeh Torabi Fatemeh Torabi true false c79d07eaba5c9515c0df82b372b76a41 Stuart Bedston Stuart Bedston true false aa1b025ec0243f708bb5eb0a93d6fb52 0000-0003-0814-0801 Ashley Akbari Ashley Akbari true false 52fc0c473b0da1b7218d87f9fc68a3e6 0000-0001-6551-721X David Ford David Ford true false db5bc529b8a9dfca2b4a268d14e03479 Emily Lowthian Emily Lowthian true false 83efcf2a9dfcf8b55586999d3d152ac6 0000-0001-5225-000X Ronan Lyons Ronan Lyons true false 0d30aa00eef6528f763a1e1589f703ec 0000-0001-5977-376X Rhiannon Owen Rhiannon Owen true false 2022-06-18 HDAT BackgroundSeveral countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.Methods and findingsWe created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.ConclusionsIn this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk–benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public. Journal Article PLOS Medicine 19 2 e1003927 Public Library of Science (PLoS) 1549-1676 22 2 2022 2022-02-22 10.1371/journal.pmed.1003927 COLLEGE NANME Health Data Science COLLEGE CODE HDAT Swansea University Another institution paid the OA fee MC_PC_19075/MRC_/Medical Research Council/United Kingdom; BHF_/British Heart Foundation/United Kingdom; MR/V028367/1/MRC_/Medical Research Council/United Kingdom; MC_PC_20058/MRC_/Medical Research Council/United Kingdom; MC_PC 19075/MRC_/Medical Research Council/United Kingdom; WT_/Wellcome Trust/United Kingdom 2022-08-16T13:22:05.1885760 2022-06-18T10:42:55.9056551 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Steven Kerr 0000-0002-3643-7859 1 Mark Joy 0000-0002-4974-3724 2 Fatemeh Torabi 0000-0002-5853-4625 3 Stuart Bedston 4 Ashley Akbari 0000-0003-0814-0801 5 Utkarsh Agrawal 0000-0001-5181-6120 6 Jillian Beggs 0000-0002-7591-3256 7 Declan Bradley 0000-0003-1468-1823 8 Antony Chuter 0000-0002-0646-5939 9 Annemarie B. Docherty 0000-0001-8277-420x 10 David Ford 0000-0001-6551-721X 11 Richard Hobbs 0000-0001-7976-7172 12 Srinivasa Vittal Katikireddi 0000-0001-6593-9092 13 Emily Lowthian 14 Simon de Lusignan 0000-0002-8553-2641 15 Ronan Lyons 0000-0001-5225-000X 16 James Marple 17 Colin McCowan 0000-0002-9466-833x 18 Dylan McGagh 0000-0002-6772-2775 19 Jim McMenamin 20 Emily Moore 0000-0002-9634-3299 21 Josephine-L. K. Murray 0000-0002-1511-7944 22 Rhiannon Owen 0000-0001-5977-376X 23 Jiafeng Pan 0000-0001-5993-3209 24 Lewis Ritchie 0000-0002-9380-7641 25 Syed Ahmar Shah 0000-0001-5672-0443 26 Ting Shi 0000-0002-4101-4535 27 Sarah Stock 0000-0003-4308-856x 28 Ruby S. M. Tsang 0000-0002-2520-526x 29 Eleftheria Vasileiou 0000-0001-6850-7578 30 Mark Woolhouse 0000-0003-3765-8167 31 Colin R. Simpson 0000-0002-5194-8083 32 Chris Robertson 0000-0001-6848-5241 33 Aziz Sheikh 34 60273__24636__f014bedb6fc74475a98351b20e442036.pdf 60273.pdf 2022-07-19T12:36:38.3372311 Output 1039438 application/pdf Version of Record true © 2022 Kerr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title 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
spellingShingle 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
Fatemeh Torabi
Stuart Bedston
Ashley Akbari
David Ford
Emily Lowthian
Ronan Lyons
Rhiannon Owen
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author_id_str_mv f569591e1bfb0e405b8091f99fec45d3
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83efcf2a9dfcf8b55586999d3d152ac6
0d30aa00eef6528f763a1e1589f703ec
author_id_fullname_str_mv f569591e1bfb0e405b8091f99fec45d3_***_Fatemeh Torabi
c79d07eaba5c9515c0df82b372b76a41_***_Stuart Bedston
aa1b025ec0243f708bb5eb0a93d6fb52_***_Ashley Akbari
52fc0c473b0da1b7218d87f9fc68a3e6_***_David Ford
db5bc529b8a9dfca2b4a268d14e03479_***_Emily Lowthian
83efcf2a9dfcf8b55586999d3d152ac6_***_Ronan Lyons
0d30aa00eef6528f763a1e1589f703ec_***_Rhiannon Owen
author Fatemeh Torabi
Stuart Bedston
Ashley Akbari
David Ford
Emily Lowthian
Ronan Lyons
Rhiannon Owen
author2 Steven Kerr
Mark Joy
Fatemeh Torabi
Stuart Bedston
Ashley Akbari
Utkarsh Agrawal
Jillian Beggs
Declan Bradley
Antony Chuter
Annemarie B. Docherty
David Ford
Richard Hobbs
Srinivasa Vittal Katikireddi
Emily Lowthian
Simon de Lusignan
Ronan Lyons
James Marple
Colin McCowan
Dylan McGagh
Jim McMenamin
Emily Moore
Josephine-L. K. Murray
Rhiannon Owen
Jiafeng Pan
Lewis Ritchie
Syed Ahmar Shah
Ting Shi
Sarah Stock
Ruby S. M. Tsang
Eleftheria Vasileiou
Mark Woolhouse
Colin R. Simpson
Chris Robertson
Aziz Sheikh
format Journal article
container_title PLOS Medicine
container_volume 19
container_issue 2
container_start_page e1003927
publishDate 2022
institution Swansea University
issn 1549-1676
doi_str_mv 10.1371/journal.pmed.1003927
publisher Public Library of Science (PLoS)
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description BackgroundSeveral countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.Methods and findingsWe created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.ConclusionsIn this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk–benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.
published_date 2022-02-22T04:18:15Z
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