TY - JOUR
T1 - Risk of myocarditis following sequential doses of COVID-19 vaccine and SARS-CoV-2 infection by age and sex
AU - Patone, Martina
AU - Mei, Xue W
AU - Handunnetthi, Lahiru
AU - Dixon, Sharon
AU - Zaccardi, Francesco
AU - Shankar-Hari, Manu
AU - Watkinson, Peter
AU - Khunti, Kamlesh
AU - Harnden, Anthony
AU - Coupland, Carol AC
AU - Channon, Keith M
AU - Mills, Nicholas L
AU - Sheikh, Aziz
AU - Hippisley-Cox, Julia
N1 - Funding Information:
This research is part of the Data and Connectivity National Core Study, led by Health Data Research United Kingdom (UK) in partnership with the office of National Statistics and funded by UK Research and Innovation (grant ref. MC_PC_20029). This project involves data derived from patient-level information collected by the National Health Service (NHS), as part of the care and support of patients with cancer. The Hospital Episode Statistics, Secondary Users Service (SUS-PLUS) datasets and civil registration data are used by permission from NHS Digital, who retain the copyright in that data. NHS Digital and Public Health England bear no responsibility for the analysis or interpretation of the data. K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands and NIHR Lifestyle Biomedical Research Centre. M.S.-H. is supported by the NIHR Clinician Scientist Award (NIHR-CS-2016-16-011). J.H.C. and K.M.C. are supported by the NIHR Oxford Biomedical Research Centre. N.L.M. and K.M.C. are supported by the British Heart Foundation (Chair Awards CH/F/21/90010, CH/16/1/32013), a Programme Grant (RG/20/10/34966), and Research Excellence Awards (RE/18/5/34216, RE18/3/34214). A.S. is supported by the Health Data Research UK BREATHE Hub, the Health Data Research Hub for Respiratory Health. The investigators acknowledge the philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the UK NIHR, or the Department of Health. The funders of this study had no role in the design and conduct of the study and did not review or approve the article. The views expressed are those of the authors and not necessarily the funders. M.P., J.H.C., and C.A.C.C. had full access to all the study data, and J.H.C. had final responsibility for submission. This project is supported by a patient and public involvement advisory panel, which the authors thank for its continued support and guidance. The input of the panel has helped the authors identify priority questions for consideration and also supported analysis. Patient and Public Involvement and Engagement advisers were supportive of the vital importance of reporting on cardiac risks associated with both vaccination against COVID-19 and COVID-19 itself.
Funding Information:
A.S. is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, the Scottish Government’s Standing Committee on Pandemics, and AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group. All roles are unremunerated. J.H.C. reports grants from the National Institute for Health Research Biomedical Research Centre, Oxford, grants from John Fell Oxford University Press Research Fund, grants from Cancer Research UK grant No. C5255/A18085 through the Cancer Research UK Oxford Centre, and grants from the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z) and other research councils during the conduct of the study. J.H.C. is an unpaid director of QResearch, a not-for-profit organization that is a partnership between the University of Oxford and Egton Medical Information Systems (EMIS) Health, who supply the QResearch database used for this work. J.H.C. is a founder and shareholder of ClinRisk Ltd and was its medical director until May 31, 2019. ClinRisk Ltd produces open and closed source software to implement clinical risk algorithms (outside this work) into clinical computer systems. J.H.C. is chair of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) risk stratification subgroup and a member of Scientific Advisory Group for Emergencies (SAGE) COVID-19 groups and the NHS group advising on prioritization of use of monoclonal antibodies in SARS-CoV-2 infection. A.H. is a member of the Joint Committee on Vaccination and Immunisation. K.K. is a member of the SAGE. The other authors declare no conflicts.
Publisher Copyright:
© 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.
PY - 2022/8/22
Y1 - 2022/8/22
N2 - BACKGROUND: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain.METHODS: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test.RESULTS: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]).CONCLUSIONS: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.
AB - BACKGROUND: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain.METHODS: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test.RESULTS: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]).CONCLUSIONS: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.
KW - 2019-nCoV vaccine mRNA-1273
KW - BNT162 vaccine
KW - COVID-19
KW - COVID-19 vaccines
KW - ChAdOx1 nCoV-19
KW - Myocarditis
KW - SARS-CoV-2
U2 - 10.1161/CIRCULATIONAHA.122.059970
DO - 10.1161/CIRCULATIONAHA.122.059970
M3 - Article
C2 - 35993236
SN - 0009-7322
VL - 146
SP - 743
EP - 754
JO - Circulation
JF - Circulation
IS - 10
ER -