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A study published in The Lancet Child & Adolescent Health looks at myocarditis and vascular and inflammatory diseases after COVID-19 infection and vaccination in children.
Prof Saidi (Sam) Mohiddin, Consultant Cardiologist, Barts Heart Centre, Barts NHS Trust; and Honorary Professor, William Harvey Research Institute, QMUL, said:
“The study looked back at electronic health records of many million young people (98% of England’s population under 18 years of age) in order to compare risks of adverse outcomes following COVID-19 infections with those associated with COVID-19 vaccination. The authors focus primarily on cardiovascular complications associated with COVID-19 vaccination that have received a lot of attention from both the public and from health professionals; these are inflammation of heart muscle (myocarditis) and inflammation of the lining of heart’s muscle (pericarditis).
“Their findings indicate that myocarditis and pericarditis are both very rare complications following either COVID-19 infections or COVID-19 vaccination, and are significantly less likely to occur after COVID-19 vaccination than after COVID-19 infection. Also notable was that risks of these outcomes were elevated for far longer after COVID-19 infection (for a year or longer) than they were following a first COVID-19 vaccination (for about 4 weeks).
“These findings are very much in line with previously published data in other populations, extending knowledge in this area to include younger age-groups. The authors conclude that because COVID-19 infection causes ‘more frequent and persistent risks’ than the COVID-19 vaccine does, their findings provide support for COVID-19 vaccination strategies in children and young people.
“The study’s strengths include the very large number of children and young people studied, particularly as this will allow more subtle associations between infection and/or vaccine with other outcomes to be explored in subgroups – for example on the basis of ages, sex, deprivation scores, co-morbidities and so on. This will help refine how the data can be used to focus vaccination strategies, and may also help us understand why myocarditis and pericarditis occur.
“ Like all research, this large study does have its limitations. It also helps define other important research questions.
“1. The authors include myocarditis and pericarditis as a single outcome, and this is almost certainly because of limitations in how electronic health records are coded. From a clinical perspective, these two conditions can be quite different, with myocarditis the greater risk to patient safety. It’s possible that infection and vaccination can cause different proportions of myocarditis and pericarditis. For risk-benefit assessments, focusing on the more serious condition may be more helpful.
“2. This study reports that myocarditis and pericarditis develop in the 4 weeks following the first dose to a COVID-19 vaccine. However, most cases of myocarditis reported in the medical literature after COVID-19 vaccination occur within a few days of a second or third dose, and only rarely after a first dose. As the exposure- and time- dependent relationship between vaccination and myocarditis is an important immunological clue as to why vaccination can result in these inflammatory complications, this apparent contradiction needs further exploration.
“3. How can these important findings be put to best use to improve the public’s health following any future outbreaks of novel COVID-19 variants, or even due to other viruses? As the authors of this study acknowledge, the risks of poor outcomes in young people following acute COVID-19 infections fell between succeeding variant (alpha, delta, omicron etc) waves. It is also known that different vaccines are associated with different risks of adverse outcomes. Accordingly, as both risks and benefits change over time, it will need to be better understood if/how these data can, in the words of the authors, ‘support the public health strategy of COVID-19 vaccination in children and young people’.
“4. Why do some people develop myocarditis after COVID-19 vaccines or virus, when the vast majority do not? This is an active area of research in which our group have recently published novel findings that suggest that certain components of the COVID-19 virus and COVID-19 vaccines can resemble normal heart proteins, tricking susceptible immune systems into attacking healthy heart muscle. A deeper understanding of the biological mechanisms causing these complications will help scientists develop better vaccines as well as more effective treatments when these rare complications occur. (For reference, own work can be found here: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074644?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed).
“In conclusion, this study’s key finding aligns with other large studies: the risk of myocarditis from COVID-19 vaccination is very low and lower than the risk from COVID-19 infection. We also know, from other studies, that most cases of myocarditis fully recover. These are pivotal factors in determining vaccination strategies.
“In order to further improve the safety of these (and other vaccines), we must better understand the mechanisms by which a very small number of susceptible individuals develop this rare complication.”
Rachel Richardson, Acting Head of Methods Support, The Cochrane Collaboration, said:
“The major strengths of this study are its size and its use of multiple sources of information to obtain data on COVID-19 diagnoses, vaccination and rare heart complications amongst children and young people. Using big data from NHS electronic health records means that the authors have able to assess the incidence of these rare complications, which can be difficult to detect in smaller samples. Perhaps the most important limitation of the study (acknowledged by the authors) is that they may have missed some cases of COVID-19 due to unrecorded and undetected infections. However, the overall size of the study, which included 3.9 million COVID-19 diagnoses in children and young people, mitigates this limitation.”
Prof Sir Terence Stephenson, Nuffield Professor of Child Health, UCL, said:
“Very reassuring to learn that the risk of covid infection leading to inflammation of the heart in children and young people was much higher than the risk from a Covid vaccine. This was a very large, powerful population based study using anonymised electronic health records from across England.”
Dr Adam Jacobs, Executive Director and Strategic Consultant, Biostatistics, Ergomed, said:
“Although covid-19 vaccines are effective in reducing the risk of death or serious infection with covid-19, one concern that has been raised about their safety is a potentially elevated risk of myocarditis or pericarditis following vaccination. Sampri et al investigated this risk in children in an impressive study using health records from NHS England, which included almost 14 million children. Not only did it investigate the risk of myocarditis or pericarditis following vaccination, it also investigated the risk after covid-19 infection, which is important to bear in mind by way of perspective.
“Although a slightly increased risk of myocarditis or pericarditis was confirmed after covid-19 vaccination with the Pfizer-BioNTech mRNA vaccine, it was still a rare event, and the elevation of risk was only temporary, being significantly elevated only in the first 4 weeks after vaccination. Crucially, the elevation in risk after vaccination was considerably lower than the elevation in risk after covid-19 infection. Thus avoiding vaccination is not a sensible strategy for reducing myocarditis or pericarditis risk, as covid-19 infection then becomes more likely which results in a higher risk of myocarditis or pericarditis than vaccination. The elevation of risk was also more persistent after covid-19 infection, remaining significant up to a year. The absolute excess risk of myocarditis or pericarditis in the 6 months following vaccination was 0.85 cases per 100,000, compared with 2.24 cases per 100,000 in the 6 months after covid-19 infection.
“Sampri et al also investigated other cardiovascular outcomes after covid-19 vaccination or infection, namely arterial thrombotic events, venous thrombotic events, inflammatory conditions, and thrombocytopenia. The risk of all those other events was significantly elevated after covid-19 infection, but the only risk significantly elevated after vaccination was that of myocarditis or pericarditis.
“This study has the strength of being a population-wide study, which largely removes problems of selection bias, and also gives good statistical power to quantify even the rare events observed. One limitation is that covid-19 infections would not necessarily always have been recorded in medical records, so some of the patients in the control group may also have had covid-19. This would have the effect of diluting the association between infection and adverse outcomes, so in fact that risk of adverse outcomes observed after covid-19 infection may actually be higher than that estimated in the paper. In contrast, vaccination is likely to be more completely recorded in medical records, so the risk estimates after vaccination should be more reliable.
“On the whole, this is a well conducted study that should give reassurance that, while covid-19 vaccination of children is not 100% safe, it is certainly safer than leaving them unvaccinated and at risk of covid-19 infection.”
Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:
“This major new study used linked health data from 13.8 million children in England to study the relationship between COVID, mRNA vaccination and inflammatory disorders. It confirms the association between vaccination with the BTN162b2 COVID vaccine (manufactured by Pfizer/BioNTech, marketed as ‘Comirnaty’) and myocarditis/pericarditis in the month after vaccination, but puts this risk in perspective: the risk of inflammatory disorders (including myocarditis, pericarditis or thromboembolism) is much greater if children were not vaccinated but were instead infected with SARS-CoV-2.
“The incidence of post-COVID inflammatory disorders declined over time but remained elevated beyond 1 year for venous thromboembolism, thrombocytopenia and myocarditis or pericarditis. By contrast, the myocarditis or pericarditis after vaccination was usually transient.
“These findings confirm the earlier reports (2021: https://www.nejm.org/doi/full/10.1056/NEJMoa2110475) that vaccines can trigger myocarditis and pericarditis, showing that early vaccine monitoring systems were effective. The adverse effects of vaccines were nicely put into perspective by other large COVID studies (for example https://www.nejm.org/doi/full/10.1056/NEJMoa2110475 and https://www.nature.com/articles/s41591-022-01689-3.pdf).
“The study raises the question, how often are inflammatory disorders triggered by other viral infections, and how and why does the spike protein from SARS-CoV-2 appear to trigger inflammation outside the lung? Can the protective effect of vaccination be disassociated from the induction of inflammation?
“The balance of evidence presented in this excellent study supports the decision to vaccinate children during the COVID pandemic.”
Prof Adam Finn, Professor of Paediatrics, University of Bristol, said:
“This important study uses whole population data-linkage to describe associations between both COVID-19 infections and receipt of the Pfizer COVID-19 vaccine and several cardiovascular conditions including blood clots and inflammation of the heart in children aged 5-18 years in 2020-2022. They conclude that the risks of these complications were bigger and more long lasting following the infection than following the vaccination.
“While this information is important and would, of course, have been very useful if somehow it could have been known to policy advisers at the time, it is important to remember that it relates to the strains of SARS CoV2 that were circulating then (not the more benign strains circulating now) and to children most of whom had little or no immunity to the virus (unlike 5-18 years olds now, most of whom will have had the infection one or more times already).
“In general people justifiably expect the risks of vaccination of their children to be near non-existent and very much less than those of the disease being prevented, so this work encourages us to continue to improve the safety profile of the vaccines we develop to prevent this disease and potential future pandemic agents.”
‘Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records’ by Alexia Sampri et al. was published in The Lancet Child & Adolescent Health at 23:30 UK time on Tuesday 4 November 2025.
DOI: 10.1016/S2352-4642(25)00247-0
Declared interests
Prof Saidi (Sam) Mohiddin: “I am named as an inventor on a patent application by Queen Mary, University of London (see below) – I am not sure that this is directly relevant to the article. Otherwise, I have no interests to declare.
US20250145667 – PEPTIDE
Abstract: The present invention relates to peptides derived from COVID-19 virus envelope protein and spike protein. The invention further relates to polynucleotides and vectors encoding said peptides, and antibodies and chimeric antigen receptors that bind to said peptides. The invention also relates to methods of diagnosis and prediction of conditions in a subject which leverage recognition of said peptides, such as by antigen-specific T cells.
Type: Application
Filed: December 2, 2022
Publication date: May 8, 2025
Applicants: QUEEN MARY UNIVERSITY OF LONDON, BARTS HEALTH NHS TRUST
Inventors: Federica Maria MARELLI-BERG, Maria Paula LONGHI, Saidi MOHIDDIN.”
Rachel Richardson: “I have no interests to declare.”
Prof Sir Terence Stephenson: “I haven’t been involved in studies of myocarditis but in the interests of openness:
Dr Adam Jacobs: “No conflicts of interest to declare.”
Prof Peter Openshaw: “Trustee/Board Member of Academy of Medical Sciences, Science Media Centre, International Society for Resp Viruses (ISRV), and the European Scientific Working group on Influenza (ESWI);
DSMB Member/Science Advisor to Seqirus, IntegerBio, GSK, Sanofi, Moderna, Pfizer and AZ;
Research Excellence Framework (REF) Panel A and Chair UoA1 (Medicine).”
Prof Adam Finn: “AF was an investigator on trials of several COVID-19 vaccines during the pandemic and leads a large study of lower respiratory tract disease in adults funded by Pfizer which was used to evaluate the effectiveness of COVID-19 vaccines in 2021.”
This Roundup was accompanied by an SMC Briefing.