{"id":50503,"date":"2021-06-23T11:25:08","date_gmt":"2021-06-23T10:25:08","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=50503"},"modified":"2021-06-25T12:29:16","modified_gmt":"2021-06-25T11:29:16","slug":"covid-19-vaccination-in-children","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2021\/06\/23\/covid-19-vaccination-in-children\/","title":{"rendered":"Covid-19 vaccination in children"},"content":{"rendered":"<p><span style=\"font-weight: 400\">The recent <\/span><a href=\"https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use\"><span style=\"font-weight: 400\">decision<\/span><\/a><span style=\"font-weight: 400\"> by the US Food and Drug Administration (FDA) to extend an emergency use authorization (EUA) for the Pfizer-BioNTech covid-19 vaccine for children from 12 to 15 years has sparked dissent from some stakeholders. While we acknowledge the concerns of other commentators, we\u2019d argue that this was the correct decision, both for children and for the societies of which they are a part. Covid-19 poses a risk to children, and protecting them should be our primary focus. Vaccination is the best way to achieve this.<\/span><\/p>\n<p><span style=\"font-weight: 400\">An estimated 191 641 children in the US have been<\/span><a href=\"https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/cases-updates\/burden.html\"> <span style=\"font-weight: 400\">hospitalised<\/span><\/a><span style=\"font-weight: 400\"> with covid-19 at a frequency of 1-3% of cases over a 13 month period, although <\/span><a href=\"https:\/\/pediatrics.aappublications.org\/content\/early\/2021\/05\/28\/peds.2020-042929\"><span style=\"font-weight: 400\">recent data<\/span><\/a><span style=\"font-weight: 400\"> suggest that this may be an overestimate, as approximately half may reflect incidental covid-19 diagnoses in the hospital. <\/span><a href=\"https:\/\/covid.cdc.gov\/covid-data-tracker\/#demographics\"><span style=\"font-weight: 400\">Provisional reports<\/span><\/a><span style=\"font-weight: 400\"> from the US Centers for Disease Control and Prevention (CDC) note that from the start of the pandemic to the start <\/span><span style=\"font-weight: 400\">of June 2021 th<\/span><span style=\"font-weight: 400\">ere have been 441 covid-19 pediatric deaths in a sampling of 476 243 deaths for which age was available. This is therefore an undercount as an estimated<\/span><a href=\"https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid19\/index.htm\"> <span style=\"font-weight: 400\">584 284 deaths were reported to the CDC up to June 2021 <\/span><\/a><span style=\"font-weight: 400\">citing covid-19 on the death certificate and this is more consistent with<\/span><a href=\"https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid19\/excess_deaths.htm\"> <span style=\"font-weight: 400\">excess mortality<\/span><\/a><span style=\"font-weight: 400\"> data. For comparison:<\/span><a href=\"https:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/mm6214a1.htm#:~:text=Before%20varicella%20vaccination%20was%20included,the%20United%20States%20(2).\"> <span style=\"font-weight: 400\">varicella<\/span><\/a><span style=\"font-weight: 400\"> caused\u00a0 approximately 11 000 hospitalizations and 100-150 deaths per year in the pre-vaccine era.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Furthermore, in the US alone, there have been<\/span><a href=\"https:\/\/www.cdc.gov\/mis-c\/cases\/index.html\"><span style=\"font-weight: 400\"> 4018<\/span><span style=\"font-weight: 400\"> cases<\/span><\/a><span style=\"font-weight: 400\"> of<\/span><a href=\"https:\/\/rupress.org\/jem\/article\/218\/6\/e20210446\/212029\/SARS-CoV-2-related-MIS-C-A-key-to-the-viral-and\"> <span style=\"font-weight: 400\">Multisystem Inflammatory Syndrome in Children (MIS-C) up to the start of June 2021,<\/span><\/a><span style=\"font-weight: 400\"> with 35 deaths. Children also risk<\/span><a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2021.05.05.21256649v2.full.pdf\"> <span style=\"font-weight: 400\">post-acute sequelae of SARS-CoV-2 after infection (PASC)<\/span><\/a><span style=\"font-weight: 400\">, although the true significance of this is only likely to become apparent in the coming months. Given<\/span><a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(21)00790-X\/fulltext\"> <span style=\"font-weight: 400\">strong<\/span><\/a><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2101765\"> <span style=\"font-weight: 400\">evidence<\/span><\/a><span style=\"font-weight: 400\"> that vaccination can<\/span><a href=\"https:\/\/www.cdc.gov\/mmwr\/volumes\/70\/wr\/mm7013e3.htm?s_cid=mm7013e3_w\"> <span style=\"font-weight: 400\">prevent even asymptomatic infection<\/span><\/a><span style=\"font-weight: 400\">, protection should be extended to the pediatric cohort.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Transmission from children occurs<\/span><a href=\"https:\/\/www.cdc.gov\/mmwr\/volumes\/69\/wr\/mm6937e3.htm\"> <span style=\"font-weight: 400\">primarily<\/span><\/a><span style=\"font-weight: 400\"> within households rather than in schools. It is estimated that<\/span><a href=\"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/fullarticle\/2778229\"><span style=\"font-weight: 400\"> around <\/span><span style=\"font-weight: 400\">40 000 parents<\/span><\/a><span style=\"font-weight: 400\"> have been lost to covid-19 in the US, and children may have acted as the vector in some cases\u2014although we do note that in most cases of intra-household transmission,<\/span><a href=\"https:\/\/pediatrics.aappublications.org\/content\/146\/2\/e20201576?ijkey=7543ac9d228609c56f9a1f366d987d4b3aafb396&amp;keytype2=tf_ipsecsha\"> <span style=\"font-weight: 400\">adults infect children<\/span><\/a><span style=\"font-weight: 400\"> rather than the reverse. Relative to adults, children frequently present with milder symptoms, and a higher proportion are asymptomatic despite high<\/span><a href=\"https:\/\/www.jpeds.com\/article\/S0022-3476(20)31023-4\/fulltext\"> <span style=\"font-weight: 400\">viral load<\/span><\/a><span style=\"font-weight: 400\">, thus increasing the likelihood of spreading covid-19 as other hosts lose their potential for infectiousness via vaccination. Prevention requires<\/span><a href=\"https:\/\/science.sciencemag.org\/content\/early\/2021\/04\/28\/science.abh2939.long\"> <span style=\"font-weight: 400\">substantial<\/span><\/a><span style=\"font-weight: 400\"> non-pharmaceutical interventions within schools, which may not be universally implementable in resource-poor districts and are an ostensible barrier to normalcy in the classroom, which can have adverse educational and mental health impacts. Vaccination therefore represents a definitive path to normalcy for children.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Concerns have been raised about the regulatory pathway by which these vaccines arrive. The principal differences between emergency use authorization (<\/span><a href=\"https:\/\/www.fda.gov\/media\/142749\/download\"><span style=\"font-weight: 400\">EUA<\/span><\/a><span style=\"font-weight: 400\">) and biologics license application (<\/span><a href=\"https:\/\/www.fda.gov\/media\/139638\/download\"><span style=\"font-weight: 400\">BLA<\/span><\/a><span style=\"font-weight: 400\">) pathways are a minimum of two months of follow-up for the former (via a 60 day period of active reporting including both solicited and unsolicited adverse events), but six months for the latter. Given the public health emergency posed by covid-19, vaccinations in the US have been authorized via an EUA pathway. As the vaccines have already been granted EUA for adults, the extension of the indication to younger patients is not an extension of the declaration of emergency to children; rather, it is representative of the scope of the existing public health crisis, the inherent risk to children, and the ability for children to serve as vectors to the most vulnerable members of society. It is<\/span><a href=\"https:\/\/vaccine-safety-training.org\/tl_files\/vs\/pdf\/13164.pdf\"> <span style=\"font-weight: 400\">unlikely<\/span><\/a><span style=\"font-weight: 400\"> for any non-live vaccine to produce adverse events beyond two months after vaccination and we are unaware of any examples in which this has occurred. Thus, given the present emergency, a four month delay to access is unlikely to produce any meaningful new safety data, but will ensure preventable harm in children who develop covid-19.\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">The limiting variable for sensitivity to capture rare adverse events following immunization (AEFI) is most properly regarded as the sample size rather than the duration of follow up. Historically, phase III trials for vaccines have included as few as 5000 individuals, and even<\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0264410X19301549?via%3Dihub\"> <span style=\"font-weight: 400\">fewer<\/span><\/a><span style=\"font-weight: 400\"> when examining specific subpopulations as is the case here; <\/span><a href=\"https:\/\/www.aappublications.org\/news\/2021\/05\/06\/moderna-covid-vaccine-teens-050621\"><span style=\"font-weight: 400\">Moderna\u2019s TeenCoVe<\/span><\/a><span style=\"font-weight: 400\"> study includes 3235 individuals aged 12-17 years and <\/span><a href=\"https:\/\/www.cdc.gov\/vaccines\/acip\/meetings\/downloads\/slides-2021-05-12\/02-COVID-Perez-508.pdf\"><span style=\"font-weight: 400\">Pfizer\u2019s trial<\/span><\/a><span style=\"font-weight: 400\"> includes 2260 individuals aged 12-15 years. Certainly, it would be unreasonable to expect trials of this size to <\/span><a href=\"https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/00031305.1997.10473947#:~:text=The%20Rule%20of%20Three%20states,samples%2C%20and%20propose%20some%20alternatives.\"><span style=\"font-weight: 400\">capture<\/span><\/a><span style=\"font-weight: 400\"> very rare AEFIs. Even if 30 000 individuals receive a vaccine in a clinical trial, events rarer than 1 per 10 000 doses are likely to be missed\u2014hence a reliance on pharmacovigilance for the detection of rare AEFIs. The sensitivity of current surveillance appears robust as recently demonstrated by the cases of<\/span><a href=\"https:\/\/www.hematology.org\/covid-19\/vaccine-induced-immune-thrombotic-thrombocytopenia#:~:text=Clinical%20and%20laboratory%20characteristics%20of%20TTS%20have%20recently%20been%20reported.&amp;text=This%20syndrome%20has%20been%20termed,by%20the%20CDC%20and%20FDA.\"> <span style=\"font-weight: 400\">thrombosis with thrombocytopenia syndrome (TTS)<\/span><\/a><span style=\"font-weight: 400\"> associated with the Janssen (Ad26.COV2.S) vaccine: an event that was initially noted in fewer than one per million doses. More recently, <\/span><a href=\"https:\/\/www.sciencemag.org\/news\/2021\/06\/israel-reports-link-between-rare-cases-heart-inflammation-and-covid-19-vaccination\"><span style=\"font-weight: 400\">questions<\/span><\/a><span style=\"font-weight: 400\"> have arisen around the possibility of myocarditis from (in particular) the second dose of the BNT162b2 mRNA vaccine in young males, but these risks remain unconfirmed at this time, and the <\/span><a href=\"https:\/\/pediatrics.aappublications.org\/content\/early\/2021\/06\/02\/peds.2021-052478\"><span style=\"font-weight: 400\">associated cases<\/span><\/a><span style=\"font-weight: 400\"> reported to date have been predominantly mild. Consequently, the balance of risks and benefits still <\/span><a href=\"https:\/\/newsroom.heart.org\/news\/covid-19-vaccine-benefits-still-outweigh-risks-despite-possible-rare-heart-complications\"><span style=\"font-weight: 400\">remains highly favorable<\/span><\/a><span style=\"font-weight: 400\"> even if the finding is found to be causal\u2014though patients should be apprised accordingly.\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">We additionally note that vaccination is an essential public health intervention that protects the vaccinee (<\/span><a href=\"https:\/\/academic.oup.com\/aje\/article-abstract\/133\/4\/323\/166589?redirectedFrom=fulltext\"><span style=\"font-weight: 400\">direct vaccine effects<\/span><\/a><span style=\"font-weight: 400\">) and the population (<\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4635729\/\"><span style=\"font-weight: 400\">indirect vaccine effects<\/span><\/a><span style=\"font-weight: 400\">). The true value of any vaccination campaign is measured by the public health gains incurred rather than the value to any given individual, which is especially apparent for diseases like chickenpox, rubella, and even<\/span><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMp2034765\"> <span style=\"font-weight: 400\">measles<\/span><\/a><span style=\"font-weight: 400\">. Those<\/span><a href=\"https:\/\/www.kff.org\/other\/state-indicator\/distribution-by-age\/?currentTimeframe=0&amp;sortModel=%7B%22colId%22%3A%22Location%22%2C%22sort%22%3A%22asc%22%7D\"> <span style=\"font-weight: 400\">under the age of 18 make up 23.6% of the US population<\/span><\/a><span style=\"font-weight: 400\">; while the herd immunity threshold for covid-19 is<\/span><a href=\"https:\/\/www.nytimes.com\/2020\/12\/24\/health\/herd-immunity-covid-coronavirus.html\"> <span style=\"font-weight: 400\">unknown<\/span><\/a><span style=\"font-weight: 400\">, it is unlikely that leaving nearly one quarter of the country unvaccinated is conducive to its attainment. Thus, even if one disregards the risks posed by covid-19 to the pediatric population directly, there is still considerable benefit to ensuring their vaccination.<\/span><\/p>\n<p><span style=\"font-weight: 400\">In our view, the current evidence unequivocally supports that the potential benefits far outweigh the potential risks of this choice. We should pursue this opportunity in an equitable manner, rather than minimizing covid-19 and perseverating on unsubstantiated concerns.<\/span><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Edward Nirenberg<\/strong> is a science communicator and vaccine advocate. He has no conflicts to declare.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Daniel A. Freedman<\/strong> is a pediatric neurologist at Dell Medical School. He has no interests to declare.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Risa Hoshino<\/strong> is a practicing board-certified pediatrician working in public health. She has no interests to declare.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Jonathan Howard<\/strong> is an associate professor of neurology and psychiatry at NYU Langone School of Medicine. He has no interests to declare.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Alastair McAlpine<\/strong> is a pediatric infectious diseases physician at BC Children\u2019s Hospital. He has no interests to declare.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Acknowledgements<\/strong>: We would like to extend our sincerest gratitude to Senior Pharmaceutical Regulatory Affairs Specialist, Andrea Bailey, PhD, for her editorial assistance and consultation for this work.<\/span><\/em><\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The recent decision by the US Food and Drug Administration (FDA) to extend an emergency use authorization (EUA) for the Pfizer-BioNTech covid-19 vaccine for children from 12 to 15 years [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2021\/06\/23\/covid-19-vaccination-in-children\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":66,"featured_media":50504,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[223],"tags":[],"class_list":["post-50503","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-guest-bloggers"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - 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