COVID-19 Vaccines for Children
By Prof. Suranjith L. Seneviratne, Danuksha K. Amarasena, Dr. Widuranga Wijerathne, Dr. Pamodh Yasawardene, Dilanthi Jayamanne
Several safe and effective COVID-19 vaccines have so far been given to millions of adults across the world. These vaccines were initially given to health and social care workers, older persons and adults with underling health conditions. Subsequently, healthy adults have been vaccinated. The Pfizer vaccine was initially authorised for persons 16 years and older and the Moderna, Oxford-AstraZeneca, Johnson and Johnson, Sputnik, Sinopharm and Sinovac vaccines for 18 years and older. The place of COVID-19 vaccines for adolescents and children, has been discussed in recent months and some countries have already started vaccinating adolescents.
In general, children infected with the SARS-CoV-2 virus develop mild disease or are asymptomatic. However, some children may get serious inflammatory complications that may adversely affect their health and well-being. COVID-19 may rarely cause death in children although the rate is much lower than in adults. Between March 2020 and February 2021, COVID-19 caused 25 deaths in children and young persons in England. About half of those deaths were in individuals with an underlying disability and high healthcare needs. In June 2021, the CDC noted that among 204 adolescents hospitalised for COVID-19, there were no deaths but nearly a third were admitted to intensive care units and roughly 5 per cent required invasive mechanical ventilation. Some children, may get the condition called Long-COVID, following a mild SARS-CoV-2 infection. This may have health impacting effects that could continue for weeks or months beyond an initial mild illness.
Children with mild symptoms, may spread the virus between themselves and to adults in their family and outside their home. Older children tend to transmit the virus more easily than younger children. An argument has been put forward, that it is important to vaccinate adolescents and children at some point to reduce such transmission and protect the health of the broader community. Each child or adult that is infected with the coronavirus provides a chance for the virus to mutate and create a viral variant that might prove more dangerous or resistant/less immunogenic to the available vaccines and treatments. Fewer infections among the population mean less potential for the appearance of new SARS-CoV-2 viral variants.
Recently, in some countries, the number of COVID-19 cases has been higher in younger persons compared to the older population. For instance, during the week ending 20th June, the infection rate among the 10 to 19-year-old group was the second highest in England and more than 17 times higher than the over-70s group. Public Health England have found the spread of SARS-CoV-2 to be particularly concentrated in schools and universities. Vaccine immunity has become increasingly important with the more transmissible Delta variant. Herd immunity against SARS-CoV-2 (either through vaccination or natural infection) is a pre-requisite to end this pandemic. Higher transmission rates increase the threshold for reaching herd immunity and vaccinating children and adolescents may be necessary for reaching such a target.
Clinical trials of COVID-19 vaccines in children
There has been a surge in the number of students missing face-to-face teaching. An increase in the rate of COVID-19 absence within State schools has been seen (5.2 per cent on 24 June and 1.1 per cent a fortnight earlier). Class closures have been highly detrimental to the education and well-being of children and adolescents. Vulnerable student groups have been disproportionately affected by this lost learning, where the absence rate in students eligible for free school meals has been higher than the total group. This article would outlined the currently (as at the end of July 2021) published information on COVID-19 vaccines in young persons.
In a recent study of 2,260 adolescents, the Pfizer vaccine was found to have 100 per cent efficacy in children between the age of 12 and 15 years. The vaccine was well tolerated and neutralising antibody levels were higher than that found in a slightly older group. Children between the ages of 5-11 years, 2-5 years and 6 months-2 years are been vaccinated in several countries as part of a clinical trial to assess its safety, immunogenicity and effectiveness. Last week, the US Food and Drug Administration (FDA) requested both Pfizer and Moderna to increase the number of 5 to 11-year-olds who participate in trials of their vaccines to 3,000 children.
In a recent study, 3,732 US children, 12 – 18 years were randomised 2:1 to receive the Moderna vaccine (100 microgram dose) or placebo. Non-inferior immunogenicity was found when compared to the Phase 3 Moderna adult study. Fourteen days after the second injection, the number of cases of COVID-19, was zero for those receiving the vaccine and four in the placebo group. The vaccine was well tolerated. Currently, the KidCOVE study, a collaboration with the National Institute of Health in the US, is studying the Moderna vaccine in children younger than 12 years. In this group the older children are to be vaccinated first and smaller doses would be used initially and then the dose would be increased.
Sinovac (CoronaVac) vaccine
Results from the phase 1 and phase 2 clinical trials of the CoronaVac vaccine, in 552 healthy children and adolescents (between the ages of 3 to 17) were recently published. The studies were done from 31st October to 30th December 2020 in the Hebei Province, China. The phase 1 and 2 trials were on 72 and 480 participants respectively. The CoronaVac vaccine was found to be well tolerated and safe. Injection site pain was the most frequently reported event occurring in around 16 per cent of those receiving the 3.0 microgram dose. In the phase 2 trial neutralising antibody responses were seen in over 96 per cent of the participants that received the CoronaVac vaccine. Higher titres of neutralising antibodies were found when compared with adults aged 18 – 59 years who received the same vaccine. Among the two doses evaluated, the neutralising antibody titres induced by the 3.0 microgram dose were higher than those induced by the 1.5 microgram dose. There was no difference in side effects between the two doses.
According to a recent press release, the Sinopharm Phase 1 and 2 clinical trials have been completed on persons aged 3 to 17 in the Henan Province and the vaccine was found to be effective and safe. The vaccine showed a good safety profile with no severe adverse effects. All the trial participants had generated antibodies after receiving two doses of the vaccine and there was no significant difference in the strength of the immune response when compared to adults. The trial had initially been carried out among adolescent 13- to 17-year-olds. It was then extended to 6-to 12-year-olds and 3- to 5-year-olds. On 6 June 2021, another study commenced in the United Arab Emirates, to evaluate the efficacy of the Sinopharm vaccine in a group of 900 children (from different nationalities) between the ages of 3 and 17 years.
Safety of COVID-19 vaccines in children
Most experts believe the COVID-19 vaccines are safe for adolescents. As children younger than 12 years are at a key stage of growth and development, the long term effects of any COVID-19 vaccine should be closely monitored. A potential link between myocarditis and pericarditis and the Pfizer vaccine has been reported. However, doctors are yet to establish that the vaccine caused the inflammation. The risk is extremely low. When all age groups were considered, 1,226 cases (from 300 million Pfizer or Moderna doses) have been reported. There were 270 cases in the 16 to 19-year group and a smaller number of younger children. The incidence is higher in young men. Almost all show full recovery and there have been no deaths. In addition, myocarditis can also be caused by other viruses and some medical treatments. In June, the US FDA added a warning about the risk of myocarditis and pericarditis, to the fact sheets of both the Pfizer and Moderna vaccines.
On 5th May 2021, Canada approved the Pfizer COVID-19 vaccine for use in children aged 12 – 15 years and then on 10th May 2021, the FDA expanded the emergency use authorisation (EUA) for the Pfizer COVID-19 vaccine to include adolescents 12 through 15 years of age. The FDA amended the EUA originally issued on 11th December 2020 for administration in individuals 16 years of age and older. On 28th May 2021, the European Medicine Agency’s (EMA’s) human medicines committee (CHMP) recommended granting an extension of indication for the Pfizer COVID-19 vaccine (Comirnaty) to include use in children aged 12 to 15. In early June 2021, the MHRA in the UK, approved the use of the Pfizer vaccine for 12 to 15-year-olds. Furthermore, on 23rd July 2021, the EMA recommended granting an extension of indication for the Moderna COVID-19 vaccine (Spikevax) to include use in children aged 12 to 17 years. In June and July 2021, the Sinovac (Coronovac) and Sinopharm vaccines were authorised for emergency use in young people (3 – 17 years), by the Joint Prevention and Control Mechanism of the State Council in China. The World Health Organization’s (WHO) Strategic Advisory Group of Experts has stated that the Pfizer vaccine is suitable for use by people aged 12 years and above
United States and Canada
Canada became the second country to authorise and use the Pfizer vaccine for children between the age of 12 and 15 years and the roll-out commenced from 12th May 2021. Algeria had already allowed the use of the Pfizer vaccine for this age group of children in April 2021. According to the Centres for Disease Control and Prevention (CDC), by 22 July 2021, about 7 million adolescents (ages 12 to 17 years) in the US, have been fully vaccinated (that is two weeks after the second dose) with the Pfizer vaccine. Another 600,000 or so adolescents were to be fully vaccinated in the next two weeks. Thus, about 30 per cent of the roughly 25 million 12- to 17-year-olds in the US would be fully vaccinated by the time the next school term starts in early August 2021.
European Union and the United Kingdom
In the EU, 20 countries are vaccinating those aged 12 and over or planning to do so in the near future. In addition, six countries have decided to initially offer the COVID-19 vaccine to children with underlying health conditions. In the UK, the Pfizer COVID-19 vaccine has been authorised for children aged 12 and over. It had already been recommended that at-risk young people aged 16-17 should be offered the COVID-19 vaccine. Recently, the UK’s Joint Committee on Vaccination and Immunisation (JCVI) announced that children aged 12-15 who are at increased risk of serious illness from infection with SARS-CoV-2 should be offered the Pfizer vaccine. This was to include children with severe neuro-disabilities and those with underlying conditions that result in immunosuppression. Children aged 12-17 who live with an immunosuppressed person were to also be offered the vaccine.
Singapore, Japan, Israel, China, Hong Kong, Philippines and the United Arab Emirates are offering the Pfizer COVID-19 vaccine to all those aged 12 and over. Several cities in China are to commence administering the Sinovac and Sinopharm COVID-19 vaccines to teenagers aged 12 to 17 and it is planned to vaccinate a large proportion of this group by end of September or October 2021.
Is the process of vaccinating children really fair?
Currently, many countries are struggling to control the spread of the SARS-CoV-2 virus and there is a critical global shortage of COVID-19 vaccines. For instance, less than 30 per cent of the population in Peru, Colombia and Paraguay have received even one dose of a COVID-19 vaccine and some of these countries have the highest COVID-19 death rates. The WHO has taken a position that it is less urgent to vaccinate children 12 and 15 years, unless they are part of a high-risk group. However, a counter argument put forward is that the number of doses needed to vaccine adolescents is not high and that global vaccine supplies would not be compromised to a great level by doing so.
Currently, adolescents in some countries are receiving the COVID-19 vaccine. Whilst all children older than 12 are offered the vaccine in some countries, only those at high risk of COVID-19 are considered in other countries. Clinical trial date on safety, immunogenicity and efficacy and real world data on effectiveness of COVID-19 vaccines in children and adolescents should become more defined in the coming months.