It was more than a year after adults began receiving COVID-19 vaccinations that regulators approved the jabs for children. The gap left some parents anxious to protect their kids, and others wondering about the vaccines’ safety and effectiveness.
About 120 countries have now authorized COVID-19 vaccines for use in children, reaching hundreds of millions of arms. The majority of vaccines have been approved for children aged five and older, but a dozen or so countries have also started to administer them to infants from six months old. The most popular shot is the mRNA vaccine developed by Pfizer and BioNTech, now approved in more than 100 countries.
Data are trickling out on how they fare against the coronavirus SARS-CoV-2, and in particular the potent Omicron variant. Information is patchy because of the variant’s late emergence, and the millions of kids who had already been exposed to the virus by the time roll-outs started. Many governments also cut back on regular testing for COVID-19, meaning that the period of rich data on infections and vaccines is effectively over. “For us, it’s an end of an era,” says Ran Balicer, an epidemiologist at the health-care provider Clalit Health Services in Tel Aviv.
Nature spoke to researchers about how safe and effective the vaccines are, how popular they have been and whether parents should vaccinate their kids if offered the chance.
How safe and effective are the vaccines in children?
By far the most widely used vaccines in kids are ones based on mRNA, offered in close to 90% of the countries and regions that have approved vaccines for kids, according to an analysis prepared for Nature by the health-analytics firm Airfinity. The mRNA vaccines “are really safe vaccines for everybody, including children”, says Kawsar Talaat, an infectious-disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. Given to billions of adults before being used in children, they have an “unparalleled” safety record, she says.
Some individuals, especially boys and men aged 16–24, develop inflammation of the heart muscle and its outer lining — conditions known as myocarditis and pericarditis — after receiving the mRNA vaccines. But those cases are rare, generally mild and resolve on their own. Cases in kids aged 5–11 are extremely rare — around one in every million children vaccinated. In fact, side effects from the vaccines, such as headaches and fever, have mostly been mild in young children1.
FDA authorizes COVID vaccines for the littlest kids: what the data say
So the vaccines are extremely safe, but how effective they are is a trickier question to answer — especially with Omicron complicating the picture. The vaccines were designed using the original SARS-CoV-2 virus, and many of the trials in children were conducted when earlier, less immune-evasive and less contagious variants such as Delta were circulating.
The data, which relate largely to the mRNA shots developed by Pfizer and BioNTech, and by Moderna, reveal that in the face of Omicron, the vaccines are good at preventing severe disease, but are less effective at limiting infection — and this protection wanes rapidly. These findings largely correspond with what happens in adults.
Studies from Singapore2, the United States3 and Italy4 find that two shots of the Pfizer–BioNTech vaccine offer moderate to good protection against hospitalization in kids aged 5–11 and in adolescents, reducing the risk by between 40 and 83%. Estimates of protection levels vary widely by country and region, depending on factors such as the time elapsed since participants’ vaccination, testing intensity and previous waves of infection.
Some countries have also begun offering children, particularly adolescents, a third dose, and these boosters seem to be effective, according to US data5: five months after adolescents received a second dose of the Pfizer vaccine, when their protection against visits to emergency-care units had fallen to zero, a booster restored that protection to 81%.
Vaccines also protect against a rare but serious complication of COVID-19 known as multisystem inflammatory syndrome in children (MIS-C). It’s not clear, however, whether vaccines can help to reduce the paediatric incidence of long COVID, a condition in which people experience symptoms months after being infected. Several studies have shown that children who test positive can develop lasting symptoms, but estimates of the prevalence in kids vary widely6,7 — from as low as 2% to as high as 66% — owing to differences in study design and how researchers define the condition.
However good they are at stemming severe disease, the vaccines do not seem to offer kids much protection from infection in the face of Omicron. One study from Qatar, posted online in July without peer review8, found that administration of two doses of the Pfizer vaccine was 26% effective at preventing infection in children aged 5–11, and that protection waned to negligible levels three months after the second dose. Adolescents had higher levels of protection and it waned more slowly.
Kids and COVID: why young immune systems are still on top
This is probably because adolescents received a larger vaccine dose, says study co-author Hiam Chemaitelly, an infectious- diseases epidemiologist at Weill Cornell Medicine–Qatar in Doha. Those aged 12 and above get 30 micrograms of vaccine, but younger children receive 10 micrograms, which “was no match for the immune evasion of Omicron”, Chemaitelly says. In each age bracket, the Qatar data showed that the vaccines were more effective at the younger end — at which kids get a higher dose relative to their size.
Children aged six months to four years are the most recent age group for which vaccines — mostly mRNA shots — have been approved. Data on how well the shots work in this group is scarce; the jabs were approved on the basis of small trials involving a few thousand children, which were designed primarily to assess safety and dosing. “A lot of the data for paediatric vaccines is inadequate and requires us to connect the dots,” says Peter Hotez, a paediatric vaccine scientist at Texas Children’s Hospital in Houston. Since June, when the United States approved vaccines for use in this age group, some 8% of kids under 5 there have had at least one dose, but weekly vaccination rates have been dropping.
The vaccines seem to work just as well at younger ages, according to preliminary data from trials. In August, Pfizer reported that three doses of its vaccine had an efficacy of 76% in preventing COVID-19 in kids aged 6 months to 2 years and 72% in those aged 2–4 years, at a time when the BA.2 Omicron variant was circulating (see ‘Vaccine versus Omicron’).
Sources: Pfizer/Ref. 3
About two dozen countries have approved two Chinese inactivated-virus vaccines — one produced by Beijing-based company Sinovac, and another produced by state-owned Sinopharm, also based in Beijing — for children as young as 6 months. Data from Argentina, Brazil and Chile show that administration of two doses of these vaccines in kids aged three and older is moderately effective at preventing COVID-19, but does a better job of protecting against hospitalization.
Information on the other half-dozen vaccines is even more scarce. For example, India has approved four vaccines for use in people aged five and older, two of which have been rolled out, both in adolescents. Post-trial data on their effectiveness in kids is lacking. “We don’t have effectiveness data on adults, so it is very unlikely that we will get it in kids,” says Gagandeep Kang, a virologist at the Christian Medical College in Vellore, India.
What is the uptake in children?
Where vaccines are available, take-up in children has varied widely. Close to 90% of those aged 3–17 are fully immunized in Chile, compared with 28% of kids aged 5–11 in New Zealand and 3% of the same age group in the Netherlands (see ‘Patchy uptake’).
Source: Airfinity
“It’s been terrible,” says Yvonne Maldonado, a paediatrician and infectious-disease specialist at Stanford University School of Medicine in California, and the younger the kids, the lower the rates. One reason for the slow uptake could be the delay in getting vaccines to kids. Many parents probably wondered why they needed to vaccinate their children who had already been infected and recovered, says Fiona Russell, a paediatrician and infectious-diseases epidemiologist at the University of Melbourne, Australia.
News that Omicron was milder than previous variants also quickly spread, and hospitals weren’t as overrun as with earlier variants, owing to mass adult vaccination and access to better treatments. In some countries, such as Israel, the vaccination campaign for those aged 5–11 launched at a time when “the disease was no longer considered such a threat by the public”, says Balicer.
But that perception is incorrect, says Hotez. Public health agencies have failed to communicate the risks of paediatric COVID-19, he says. “The case has not been adequately made about the significant number of deaths and hospitalizations among kids.” And anti-vaccine groups in the United States have been especially outspoken against childhood vaccinations, he adds.
Ximena Aguilera, a public-health researcher at the University of Development in Santiago, attributes Chile’s success to the extensive network of vaccination sites, including mobile clinics at schools and neighbourhoods. Belief in the benefits of vaccination remains stronger than rumours spread by anti-vaccine groups, she adds.
Should countries be rolling out vaccines for children?
Researchers agree that vaccinating children will protect them from severe disease and death. The majority of deaths during the pandemic have occurred in people 65 and older, but more than 16,000 children under the age of 20 have lost their lives to COVID-19, and that figure “may be several times higher”, says Hotez.
In the United States, COVID-19 has killed close to 1,500 people aged 18 and under. These are “avoidable deaths”, says Maldonado. “If we can prevent deaths in children, we should do that.” And vaccines don’t just help to avert deaths, she says, they also keep kids out of hospitals. Vaccines could also better prepare children for emerging variants and the unknown long-term risks of multiple infections, says Paul Licciardi, an immunologist at Murdoch Children’s Research Institute in Melbourne.
An 8-month-old girl receives a COVID-19 vaccine in Pennsylvania in June 2022.Credit: Hannah Beier/The New York Times/Redux/eyevine
For a parent deciding whether to vaccinate their child, the costs and benefits look a little different from those for a health authority determining whether to roll out a mass vaccination programme — or to allocate precious funding elsewhere. Some researchers question the need for national vaccination programmes for healthy kids.
For many countries, access to vaccines remains a major hurdle, but in those that have approved them for children, the patchwork of regulations reflects a lack of global consensus. Data from Airfinity show that about a dozen countries, including the United States, Canada and Israel, have cleared vaccination for children from their first year of life. The majority of countries that have approved childhood vaccinations are offering them to those aged two to six, and about two dozen to adolescents only (see ‘Approvals by age’). Some nations, such as Denmark, are not offering COVID-19 vaccines to healthy children.
Source: Airfinity
Once again, “Omicron changed the game”, says Shamez Ladhani, a paediatric infectious-diseases physician at St George’s, University of London. It meant the vaccines were less potent at preventing infection and onward spread, and any protection waned rapidly. They do offer protection against severe disease, but the risk is lower to begin with, especially in younger children, says Ladhani. For example, a US study of kids aged 5–11, conducted when Omicron predominated, estimated that vaccination reduced the risk of hospitalizations from 19 to 9 admissions per 100,000 infections9. “The numbers are so tiny that you lose precision,” says Ladhani.
The large number of kids who have already had COVID-19 also “changes the calculus as to the benefit of vaccines”, says Shabir Madhi, a vaccinologist at the University of the Witwatersrand in Johannesburg, South Africa, because these children have gained some immunity to the virus, and infections are expected to be less severe the second or third time around.
What COVID vaccines for young kids could mean for the pandemic
Some 59 million young people under the age of 20 are reported to have had COVID-19 at some point since the pandemic began. And many more infections have gone undetected, as studies that test for the presence of antibodies against SARS-CoV-2 — a marker of past infection — have shown. Data from South Africa10 suggest that, by early 2022, 84% of children under 12 had been infected.
But vaccines can provide an advantage even to those who have been infected. Studies in adults have shown that those who were vaccinated and contracted COVID-19 were best protected, and studies in children support those findings. “Hybrid immunity is still the best immunity you can get,” says Ladhani. He and his colleagues found that adolescents in England who had been vaccinated and had been previously infected with Omicron had almost complete protection against a second Omicron infection, as described in a preprint posted on 22 August11.
But Madhi says that it still isn’t clear what extra benefit against severe disease a healthy child who has previously been infected with SARS-CoV-2 would get from being vaccinated. And researchers agree that vaccinating kids has a small and short-lived effect on reducing community transmission.
Children with pre-existing conditions or compromised immune systems should still get the jab, according to a recommendation from the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) in August. “We do not recommend, still, the wider use of the vaccine in younger groups, since these are not the priority,” said Alejandro Cravioto, SAGE chair, at a virtual press conference. Countries need to decide for themselves where their priorities lie, they said.
Reinforcing these sentiments is the fact that mass-vaccination programmes are expensive, and governments with limited resources have to choose which diseases to vaccinate their kids against. The Pan American Health Organization, headquartered in Washington DC, conducted an unpublished analysis for a hypothetical country of 50 million people, and estimated that vaccinating the entire population against COVID-19 would cost more than US$1 billion — 12 times the annual routine childhood vaccination budget of US$89 million. Vaccination against COVID-19 “can’t be coming at the cost of children dying of other diseases”, says Madhi.
In 2021, pandemic disruptions meant that some 25 million children missed out on routine vaccines, such as for measles, diphtheria, tetanus and whooping cough. Measles cases in Africa were fourfold higher in the first three months of 2022 compared with the same period in 2021, and other vaccine-preventable diseases are also on the rise, from polio to yellow fever.
But even a low risk of COVID-19 is still a risk. “Because this pandemic is really being driven by adults, it’s hard to remember that kids exist,” says Maldonado. But “we need to remember that all populations are affected, and that as much as possible, we build the infrastructure to support all age groups”.