Childhood vaccination is critical for Omicron and beyond

In November 2021, Canada’s National Advisory Committee on Immunization (NACI) recommended that children 5-11 get vaccinated. While there has been good progress in vaccine uptake in this age group – roughly 57% have received at least one dose – it has been insufficient to protect children in the context of the fast-spreading Omicron variant. Whereas over 2,000 children (0 to 19) had been hospitalized in Canada within the first 22 months of the pandemic, over 2,500 were hospitalized in the last three months alone (up to March 4, 2022) during the Omicron wave.

The increased number of hospitalizations among children is indicative of the need to continue to promote vaccination in this age group. Higher vaccination rates will also help to keep kids in school, encourage their social interactions, and get them into extracurricular and other activities, thus securing their mental and social well-being. In this review, we offer the latest scientific research regarding COVID-19 and vaccination in children. We also point to answers still being sought and how the CITF and its funded studies are trying to help answer those questions to broaden our understanding and improve our efforts to safeguard public health. The bottom-line messages from the experts are:

1. Evolving variants have changed the game for children
2. Vaccines can protect children against the worst effects of Omicron

Evolving variants have changed the game for children

Earlier SARS-CoV-2 variants of concern such as Alpha, Beta, and Gamma did not lead to significant upticks in pediatric hospitalizations. However, the rise of the highly transmissible Delta and Omicron variants, coupled with the loosening of public health restrictions and the vaccination of adolescents and adults, have since altered that reality (1-3). As seen in the past few months, the fast-spreading Omicron variant has increased the number of children getting infected and being hospitalized with or for COVID-19 (4).

More Canadian children need to be vaccinated

Pfizer-BioNTech’s Comirnaty COVID-19 vaccine regimen consisting of two 10 microgram doses (one third of the adolescent/adult amount) was shown to be 91% effective against SARS-CoV-2 infection in children aged 5 to 11 in a phase three clinical trial during the Delta wave (5). Based on this evidence, in November 2021 the National Advisory Committee on Immunization (NACI) recommended that Canadian children between the ages of 5 and 11 be vaccinated against COVID-19. Since then, more than 1.7 million pediatric doses have been administered in Canada. Despite this, only about 57% of children aged 5 to 11 have benefitted from at least one dose of the COVID-19 vaccine. This compares to 88% of all Canadians aged 12 to 17 having received at least one dose as of February 27, 2022. Of note, 86% of children aged 5 to 11 in Newfoundland and Labrador have received at least one dose of vaccine, making this province an exemplar of what can be achieved when resources and people come together.

It is increasingly important to recognize the multiple benefits arising from pediatric immunization against COVID-19. Above all, successful immunization campaigns will protect children from severe disease. They will also allow the re-establishment of social networks, support the continuity of in-class schooling, and permit the full resumption of extracurricular activities. Not only can pediatric vaccines protect children’s health, but they also have the potential to hasten the return to normal social interaction we have all been waiting for.

COVID-19 vaccines have raised the bar

Real-world data have shown COVID-19 vaccines to be both safe and effective  (6, 7). Since their roll-out in adults and adolescents, vaccines have significantly reduced severe outcomes (such as hospitalizations) and death caused by COVID-19 (8, 9). For instance, in Canadian adults aged 18 and older, two-dose vaccine effectiveness ranges between 80% and 95% against hospitalization and death, including during the Omicron wave (10-12). While this data bodes well for children aged 5 to 11, real-world vaccine effectiveness studies are currently underway. One study from the United States looking at 5- to 11-year-olds that has not yet undergone peer-review shows a drop in vaccine effectiveness against infection in the Omicron eracompared to what was seen in the clinical trials; however, vaccination remained protective against severe disease and death (13). Moreover, vaccines may also have a positive impact on persistent symptoms such as fatigue, headaches, and loss of smell experienced in some children previously infected with SARS-CoV-2 (14). These new data suggest that pediatric vaccination could thwart any undue morbidity in this population.

The CITF has recently invested in expanding its existing pediatric studies to support the investigation of antibody and cell-mediated immune responses to SARS-CoV-2 infection and vaccination in 200 children aged 5 to 11 years. This national study is a partnership between investigators in the CITF Pediatric Network, including existing CITF-funded pediatric study cohorts in Montreal (EnCORE), Ontario (TARGet Kids!), British Columbia (SPRING), and Winnipeg and Edmonton (CHILD Cohort).

Safeguarding children’s mental and educational health one shot at a time

Immunization of school-aged children will ensure that the education system remains safe and intact, with children attending classes and extracurricular activities in-person and experiencing the benefits of community interaction. Importantly, having children in regular school (and in summer, camp) environments assures that their social, educational, and developmental needs are adequately addressed. Furthermore, it enables parents to return to work without the concern of potential COVID-19-related school and camp closures. Vaccination will be even more crucial as masks become less prevalent in school settings. The CITF funds several studies focused on assessing the transmission and impact of COVID-19 in daycare, primary, and secondary school settings, including the toll on teachers and staff (15-17).

Canadian children are getting hospitalized and dying from COVID-19

There have been at least 22 COVID-19-related deaths in the 0-11 age range in Canada (4). Moreover, more than 4,536 children and adolescents (aged 0 to 19) have been hospitalized with or for COVID-19 since the beginning of the pandemic. Over 2,500 of these hospital admissions have occurred in the last three months, during the Omicron wave, despite the relatively mild symptoms that most experience (4).

As the world seeks more information about severe outcomes in children, Dr. Stephen Freedman heads a CITF-funded study included in the Pediatric Emergency Research Canada (PERC) network, which aims to characterize predictors and clinical outcomes of severe COVID-19 in children (including their link to variants of concern) across multiple centres in Canada and internationally with global partners (18).

COVID-19 can cause MIS-C, myocarditis, or pericarditis in children

Another side effect of SARS-CoV-2 infection is myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the sac holding the heart) (21-25). These conditions have not been extensively noted in children 5 to 11 years old and are more frequent in young adults, particularly males (26, 27). Accumulating evidence shows that the mRNA vaccine-induced version of myocarditis/pericarditis is rare, generally mild, and resolves quickly (23-26, 28). This stands in stark contrast to its SARS-CoV-2-induced counterpart, which is more severe and more long-lasting (29). As part the Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN), CITF-funded researcher Dr. Jeff Kwong from ICES is actively monitoring the prevalence of myocarditis/pericarditis following mRNA vaccines among youth in Ontario (30) .

COVID-19 symptoms could last for weeks to months in children

While there is not enough evidence to estimate the prevalence of long COVID in children, a large study from the United Kingdom has found that 1-8% of children affected by COVID-19 may experience persistent symptoms even after their infection has cleared (14). This condition has the potential to negatively impact a child’s well-being in the long-term. Over recent weeks, other researchers have followed up on this heavily-cited article indicating that this number may be a dramatic underestimation of the true extent of this condition (31). Dr. Freedman’s PERC-based study is also quantifying the burden of long COVID in children and its impact on their quality of life. The ramifications of the long-term negative health impacts post-infection may become more important as new and more transmissible variants rapidly sweep through our population.

COVID-19 vaccines are safe in children

Canada has several robust and long-standing active and passive safety surveillance systems to monitor adverse events following immunization (or AEFIs). The long-running Canadian Vaccine Safety (CANVAS) Network that monitors the safety of seasonal influenza vaccines has pivoted, with funding from the CITF, to actively monitor COVID-19 vaccine safety (CANVAS-COVID) in adolescents and adults, and more recently, in children under 12. Preliminary data from CANVAS-COVID, which can be found on their website, has reinforced the conclusion that COVID-19 vaccines are well tolerated by children and that reported AEFIs have been consistent with vaccinations for other diseases. Among more than 245,000 children surveyed seven days after their first dose, about 94% did not experience any negative health conditions that may or may not be related to the vaccine, including fever, headache, and nausea. 95% of children did not develop a health event within seven days of the second dose (36).

To address gaps pertaining to very rare severe safety concerns following immunization, the Special Immunization Clinic (SIC) Network, funded in part by the CITF and led by Dr. Karina Top from Dalhousie University, strives to standardize and improve the care of pediatric and adult patients with AEFIs (e.g., allergic reactions, Guillain-Barré Syndrome) and determine the risk of AEFIs recurring with future vaccinations. Dr. Top also leads Canada’s Immunization Monitoring Program ACTive (IMPACT), which is funded in part by the CITF. IMPACT is a pediatric hospital-based national active surveillance network for AEFIs and select infectious diseases that are vaccine-preventable, and now includes COVID-19.

Vaccines strengthen immunity in children with a previous Omicron infection

Infection builds immunity, but vaccination provides more robust protection. If a child has had a SARS-CoV-2 infection, regardless of the variant, NACI recommends that they still get vaccinated, if eligible, at least eight weeks after symptoms subside or after a positive test (if no symptoms were experienced) (32). Similarly, if a child has recovered from an infection with SARS-CoV-2 between their first and second dose, they should still receive their second dose, but should wait at least eight weeks before doing so (22). Waiting at least eight weeks after an infection will help maximize and refine immune memory and subsequent immune responses. Children who are immunocompromised are encouraged to wait at least four to eight weeks after an infection to get vaccinated (22) because they are more at risk of serious illness. Indeed, CITF-funded researchers Drs. Deepali Kumar, Juthaporn Cowan, Pascal Lavoie, Rae Young, and Sasha Bernatsky are conducting distinct studies to provide a more comprehensive overview of infection- and vaccine-induced immune responses in immunocompromised children and adolescents, including those who have received transplants and those with inflammatory bowel disease, among other conditions (33).

Since the extent of protection provided by a prior SARS-CoV-2 infection alone is unknown, eligible children should be vaccinated with the two-dose COVID-19 vaccine regimen. Importantly, provinces and territories each have their own set of guidelines for the timing of vaccines after an infection, so it is highly recommended to verify with local public health units.

Potential solution: school-based COVID-19 vaccine clinics

As mentioned above, Newfoundland and Labrador has achieved an impressive pediatric vaccination rate (87% in 5- to 11-year-olds as of February 27, 2022). Much of this success is owed to their school-based COVID-19 vaccine clinics. Delivering vaccines to the children of consenting parents during class time eases the burden on parents, is logistically sensible for vaccinators, and ensures the timely immunization of large numbers of the pediatric populations at once. In fact, many CITF researchers and experts have publicly endorsed this idea (see article in the Toronto Star).

While not all provinces and territories have moved to offering school-based clinics, many have developed unique, pediatric-focused vaccine clinics with specially trained nurses and physicians – some even with comfort dogs – to ensure that the immunization process is as fuss-free and comfortable as possible. Additionally, culturally relevant clinics for both children and adults are being offered in many Indigenous communities throughout the country.

Conclusion

Mass immunization campaigns are not new. Globally, immunization is recognized as one of the most important and cost-effective public health interventions available (34). Vaccine-preventable diseases such as measles and polio have been radically reduced thanks to immunization campaigns around the world, and the Public Health Agency of Canada estimates that immunization has probably saved more lives in Canada in the last 50 years than any other health intervention (29, 34, 35). While it is understandable for parents to have concerns when pediatric vaccines for relatively new diseases are introduced, the history of vaccination provides evidence that vaccines are a very safe and effective way to address preventable illnesses.

This pandemic has been met with an unprecedented global effort including real-time data sharing which has led to the development of very safe and effective vaccines. These vaccines continue to be monitored globally, and in Canada, by rigorous surveillance programs. Looking at the evidence, the benefits of vaccination outweigh the risks, especially as variants of concern such as Omicron continue to challenge pandemic management. More than half of all Canadian children enjoy some protection offered by COVID-19 vaccines. Hopefully, even more will take advantage in the very near future. The key is in our hands. This is our chance to allow children to fully engage with the larger world once again.

A special thanks to our experts who have contributed to this article:

Dr. Megan Azad
Dr. Scott Halperin
Dr. Jim Kellner
Dr. Jonathon Maguire
Dr. Bruce Mazer
Dr. Manish Sadarangani
Dr. Karina Top
Dr. Kate Zinszer

Prepared by:

Dr. Varun Anipindi, Senior Research Advisor, CITF Secretariat
Kristin Davis, Research Assistant, CITF Secretariat
Dr. Marija Djekic-Ivankovic, Research Associate, CITF Secretariat
Dr. Alexis Palmer-Fluevog, Research Associate, CITF Secretariat

Helpful resources

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