Vaccination recruits both the innate and adaptive immune system; COVID-19 vaccines are safe for children

In May 2021, the U.S. Food and Drug Administration (FDA) authorized the use of mRNA COVID-19 vaccines for children aged 12 to 15. The FDA later extended its authorization for children from five to 11 in October 2021 and from six months of age to four years in June 2022.

Extending COVID-19 vaccination to children and teenagers bolstered the persistent narrative that vaccines are dangerous. Health Feedback covered this claim in previous reviews, showing that available clinical data don’t support this narrative.

In March 2023, another iteration of this narrative circulated on social media. In a video on Joseph Mercola’s Instagram account, pediatrician Michelle Perro made several inaccurate and misleading claims regarding the vaccination of children against COVID-19. Mercola, an osteopath, has a history of publishing inaccurate vaccine information and has already made numerous inaccurate or misleading statements on COVID-19 and vaccination in the past.

In the video, Perro implied that children shouldn’t get vaccinated against COVID-19 on the basis that the vaccines were harmful and unnecessary for children. First, she claimed that COVID-19 vaccines were dangerous to children because they caused vaccine injuries including myocarditis. Second, she claimed that children’s immune defenses weren’t vulnerable to COVID-19 because they had a strong innate immunity, and that since this type of immunity wasn’t engaged by vaccination, vaccination was unnecessary. In this review, we will explain why Perro’s claims are inaccurate and contradicted by available clinical evidence.

Claim 1 (Inaccurate):

“clearly these vaccines are dangerous for kids”

The evidence from clinical trials in pediatric populations before COVID-19 vaccines were authorized for this population contradict Perro’s claim. Trials in children aged six months to 17 years only reported mild reactions to the vaccines and no severe vaccine-related adverse events^[1-6].

Apart from clinical trials, which are powerful tools to establish the safety and efficacy of vaccines and are critical for their authorization by health authorities, real-world data also offer their share of useful information. Monitoring the possible occurrence of adverse events following vaccination is thus an important part of post-marketing pharmacosurveillance.

To be clear, adverse events following vaccination aren’t necessarily all caused by the vaccine. The correlation between vaccination and the onset of any adverse events alone isn’t enough to show a causal association between the two and additional steps need to be taken to demonstrate causality. That being said, evidence of an abnormally high number of severe adverse events following vaccination signals a potential safety issue that requires further investigation.

This is why the U.S. Centers for Disease Control and Prevention (CDC) monitored possible adverse events through several tools. One of these, called v-safe, is a cell phone-based tool where parents can register the possible adverse events occurring in their children following vaccination. Another tool, VAERS, is a passive monitoring system, where healthcare practitioners or people from the public can declare any adverse reactions.

In the children aged six months to five years, 98% of the v-safe and VAERS reports concerned non-serious adverse events. The most common reactions were crying, pain at the site of injection or fever^[7]. These are normal reactions and the sign that the vaccine is working.

In children aged five to 11 years, most reactions to the vaccination were mild to moderate. 97% of VAERS reports were nonserious and the most common adverse events were administration errors of the healthcare staff. This means that they weren’t related to the vaccine itself in any ways. VAERS contained eleven myocarditis reports after eight million doses administered. While VAERS reports also contained two deaths of children with multiple chronic medical conditions, case reviews didn’t establish any causal association with the vaccine^[8].

Similar results were found in adolescents aged 12 to 17 years based on v-safe and VAERS data. Most people reported mild to moderate reactions such as pain, fatigue or fever. 90% of VAERS reports were nonserious. Among the serious adverse events reported to VAERS, the most common was myocarditis, which is consistent with the fact that myocarditis emerged as a rare and mild, yet detectable side effect of COVID-19 mRNA vaccination. Fourteen deaths were reported to VAERS, but a medical review of the available information showed that the causes of death didn’t show a pattern suggestive of a causal association with vaccination^[9].

Additional investigations outside of the CDC databases confirmed that COVID-19 vaccines authorized for children in the U.S. have a good safety profile. Systematic reviews of the available literature showed observations consistent with the initial clinical trials: most adverse events were mild and moderate and resolved in a matter of days. Serious adverse events were rare and transient^[10,11].

Monitoring of hospital admissions for selected medical conditions such as Guillain-Barre syndrome, neuropathy, thrombosis, stroke, seizure, anaphylaxis or myocarditis in Scotland showed no increase in hospitalization following vaccination^[12].

A preprint—an article that has not yet been peer-reviewed—reached similar conclusions. The near real-time monitoring of administrative health insurance claims in the U.S. didn’t detect any increase of claims for the list of medical conditions cited above,to the exception of myocarditis^[13].

Other researchers compared the probability of adverse events after COVID-19 vaccination with that after common childhood vaccinations like tetanus or measles/mumps/rubella. They found that the overall frequency of symptoms were comparable, indicating that mRNA COVID-19 vaccines are no different from generally accepted childhood vaccines^[14].

Altogether, these data gathered from the pre- and post-authorization periods indicate that COVID-19 vaccines are safe for children, contrary to Perro’s claim. By contrast, an analysis of the U.S. CDC’s database on underlying causes of death showed that COVID-19 was the fifth most common cause of disease-related deaths among people under 19 between August 2021 and July 2022^[15]. Since COVID-19 vaccines are highly effective at reducing the risk of developing severe COVID-19 and death, COVID-19 vaccines have a favorable risk/benefit profile in children.

Claim 2 (Misleading):

COVID-19 vaccines injure children by causing myocarditis

In her interview, Perro claimed “I was amazed how many kids I was seeing who were injured”, and cited myocarditis as an example of such injuries.

However, her claim is misleading as it lacks sufficient context about the health impact of vaccine-associated myocarditis. As we detail below, myocarditis is a rare and mild side-effect vaccination, whereas myocarditis caused by COVID-19 is more dangerous.

Myocarditis is now well-described as a possible side effect of mRNA COVID-19 vaccination that mostly occurs in young men. However, its incidence remains low. Its incidence varies between reports, but overall, the rate of myocarditis following vaccination ranges between eight to 480 cases per million doses administered^[16-19]. Furthermore, vaccine-associated myocarditis rate is even lower among young children compared to teenagers^[8].

Although myocarditis may sound worrying as it is an inflammation of the heart, many cases of myocarditis are actually benign. Meta-analyses and systematic literature reviews of vaccine-associated myocarditis in children showed that most cases had mild clinical courses and resolved with a mean hospital length stay of three days^[19-21].

A 90-day follow-up of teenagers and young adults who had vaccine-associated myocarditis revealed that 81% of the cases were considered recovered after three months with a quality of life similar to the pre-pandemic situation^[22].

The COVID-19 Real Time Learning Network, a collective of medical doctors and public health experts, also concluded that “the characteristic clinical course of vaccine-associated myopericarditis includes brief hospitalization and significant symptom improvement occurring within a week of onset, without need for higher-level care or readmission”.

Besides the considerations of vaccine-associated incidence and clinical course, it is misleading to present it as a risk without placing it in the wider context of the consequences of getting COVID-19, as Perro did.

In fact, the risk of myocarditis is actually higher following COVID-19 than following vaccination, as pediatric cardiologists explained in this article for The Conversation. Although it is difficult to obtain data specifically in the pediatric population, a study of myocarditis follow-up in Hong-Kong showed that the risk of a bad outcome, including death, is higher with COVID-19-associated myocarditis than vaccine-associated myocarditis^[23].

Another study in Nordic countries performed a 90-day follow-up of myocarditis patients. It found that the risk of heart failure and death were lower in cases of vaccine-associated myocarditis compared to those of COVID-19-associated myocarditis^[24].

In summary, scientific evidence indicates that vaccine-associated myocarditis is generally mild and resolves quickly. In contrast, getting COVID-19 carries a greater risk of myocarditis and a poorer prognosis if myocarditis does develop. All things considered, it’s clear that the evidence shows the COVID-19 vaccines’ benefits outweigh their risks.

Claim 3 (Incorrect):

Children are less vulnerable to COVID-19 because they have a strong thymus-mediated innate immune system; vaccination doesn’t use the innate immune system.

Perro also suggested that COVID-19 vaccines are unnecessary for children as they “do so well with this virus, because of their robust innate immunity which is totally bypassed when you get somebody [sic] vaccination”.

It’s true that children are less likely to develop COVID-19 compared to older people, with lower rates of cases, hospitalization or deaths. And data indicate that the innate immune system may play an important role in children’s ability to fight SARS-CoV-2 infection. However, Perro’s explanation for that phenomenon isn’t consistent with scientific evidence.

First, Perro attributed the “robust innate immunity” to the presence of a large thymus. The thymus is a crucial organ for the development of our immune system that tends to shrink as people grow older. However, the thymus is primarily associated with the development of T cells (the T stands for thymus), which are central components of the adaptive immune system, not the innate immune system^[25]. It’s unclear what the scientific basis for Perro’s claim is, since she offered no evidence for it.

Rather, several studies converged toward the idea that children benefit from a swifter engagement of the mucosal immune defenses in the airway, compared to adults. For example, the airways of children showed a higher baseline level of certain molecules that indicate innate immune system activation compared to those of adults, even in the absence of infection. This indicates that the innate immune system in children’s upper airway is preactivated, allowing for a faster response^[26-28]. Such “priming” in mucosal immunity observed in children could potentially limit the spread of SARS-CoV-2 to other parts of the body in the event of infection.

Therefore, while it is true that scientific evidence suggests the innate immune system plays a significant role in why children are less likely to develop COVID-19 and severe disease, studies so far suggest that a more reactive and “primed” mucosal immunity in the airway is an important contributor to children’s immune defenses against COVID-19. The alleged primary role of the thymus in this process, as claimed by Perro, is unsubstantiated.

Perro also claimed that COVID-19 vaccines “bypassed” the innate immune system. The basis for this claim may stem from our understanding of vaccines as primarily aimed at generating responses from the adaptive immune system, such as antibodies and the ability to “remember” the pathogen in case of future encounters. However, this doesn’t mean that the innate immune system plays no role in the body’s response to vaccination.

For example, data obtained both in mice and humans showed that the Pfizer mRNA COVID-19 vaccine stimulates the innate immune system. Indeed, vaccination of humans and mice activated cells and increased production of molecules pertaining to the innate immune response^[29-32].
A study found that this engagement of the innate immune system following vaccination was associated with a better protection of the lung tissue in case of subsequent infection by SARS-CoV-2^[33].

Another study in humans found that vaccination activated macrophages, which in turn were instrumental to activating key actors of the adaptive antiviral immune response^[34].

In summary, studies suggest that the more reactive state of children’s innate immune system plays a key role in their resistance to SARS-CoV-2 infection. While vaccination aims to stimulate antibody production and memory in the adaptive immune response, it also stimulates the innate immune system, contrary to Perro’s claim. Furthermore, this activation of the innate immune system enhances the body’s defenses against the pathogen. Therefore, Perro’s implication that the innate immune system has no role to play in vaccine-induced immune responses is incorrect.

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