The risk of myocarditis in younger males is higher following COVID-19 vaccination than infection

In younger men <40 years the risk of myocarditis was shown to be higher after vaccination than SARS-CoV-2 infection. 

Between  December  1,  2020,  to  November  15,  2021  a  total  of  42,200,614  people  were 

vaccinated  with  at  least  one  dose  of  ChAdOx1  (n=20,646,456),  BNT162b2  (n=20,391,600)  or 

mRNA-1273 (n=1,162,558) in England. Of these, 38,347,981 received 

two  doses  of  either  ChAdOx1  (n=20,059,058),  BNT162b2  (n=17,294,004)  or  mRNA-1273 

(n=1,039,919) and 10,978,507 people received a third dose of ChAdOx1 (n=35,608), BNT162b2 

(n=10,599,183)  or  mRNA-1273  (n=343,716).  Amongst  people  receiving  at  least  one  vaccine 

dose, 5,185,772 (12.3%) tested positive for SARS-CoV-2; 2,834,579 (54.7%) prior to vaccination, 

698,993 (13.5%) after a first vaccine dose, 1,604,087 (30.9%) after a second vaccine dose and 

48,113  (0.9%)  after  a  third  vaccine  dose.  Of  the  42,200,614  persons  included  in  the  study 

population, 2,539 (0.006%) were hospitalized or died from myocarditis during the study period; 

552  (0.001%)  of  these  events  occurred  during  1-28  days  following  any  dose  of  vaccine.  

Despite  more  myocarditis  events  occurring  in  older  persons,  the  risk  following  COVID-19 

vaccination was largely restricted to younger males aged less than 40 years, where the risks of 

myocarditis  following vaccination and infection were similar. However, the notable exception 

was  that  in  younger  males  receiving  a  second  dose  of  mRNA-1273  vaccine,  the  risk  of 

myocarditis  was  higher  following  vaccination  than  infection,  with  an  additional  101  events 

estimated  following  a  second  dose  of  mRNA-1273  vaccine  compared  to  7  events  following  a 

positive SARS-CoV-2 test.  


Risk of myocarditis following sequential COVID-19 vaccinations by age and sex

Martina Patone, Winnie Xue Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol AC Coupland, Keith M. Channon, Nicholas L Mills, Aziz Sheikh, Julia Hippisley-Cox
1: Nuffield Department of Primary Health Care Sciences, University of Oxford 
 2: Wellcome Centre for Human Genetics, University of Oxford 
 3: Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK 
 4: Usher Institute, University of Edinburgh, Edinburgh, UK 
 5: Centre for Inflammation Research, University of Edinburgh 
 6: School of Immunology and Microbial Sciences, King’s College London 
 7: Nuffield Department of Clinical Neurosciences, University of Oxford, 
 8: NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust 
 9: School of Medicine, University of Nottingham 
 10: British Heart Foundation Centre of Research Excellence, NIHR Oxford Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK 
 11: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK Correspondence to: Professor Julia Hippisley-Cox, Nuffield Department of Primary Care Health

Abstract

In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy.


Martina Patone, Winnie Xue Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol AC Coupland, Keith M. Channon, Nicholas L Mills, Aziz Sheikh, Julia Hippisley-Cox Risk of myocarditis following sequential COVID-19 vaccinations by age and sex  medRxiv 2021.12.23.21268276; doi: https://doi.org/10.1101/2021.12.23.21268276

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More recent papers came to the same conclusions: 

Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, Khunti K, Harnden A, Coupland CA, Channon KM. Risk of myocarditis after sequential doses of COVID-19 vaccine and SARS-CoV-2 infection by age and sex. Circulation. 2022 Sep 6;146(10):743-54.

Retrospective cohort study of 196,992 adults in Israel did not observe an increased incidence of neither pericarditis nor myocarditis in unvaccinated adult patients recovering from COVID-19 infection.

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