Study didn’t show COVID-19 vaccines weaken children’s immune response, contrary to claim by Alex Berenson

A study from researchers at the University of Melbourne^[1] became the basis of claims on social media that the Pfizer COVID-19 vaccine damaged children’s immune response against other diseases.

One example of such a claim can be seen in this article by the Florida Standard. It claimed that the study “shows weakened immune response in kids injected with Pfizer’s COVID-19 shot”. The website also added that “this caution perhaps seems like a bizarre afterthought, since children around the world are injected with mRNA COVID-19 shots as a matter of routine”. This statement implied that health authorities, vaccine manufacturers and researchers alike had overlooked a risk to children’s safety.

Another example of this claim comes from writer Alex Berenson, who claimed on his Substack page that “The mRNA Covid jabs damage immune responses to other viruses in children” and evoked a “long-term immune deficiency”.

However, this inaccurately represents the study’s findings and the study’s authors have since come forward to refute these claims, as we explain below.

What did the study do and what did it find?

The study by Noé et al. investigated off-target effects of COVID-19 vaccines in children. Off-target effects are the effects of a given vaccine on diseases other than the one they are targeting. For instance, vaccination against smallpox or tuberculosis is associated with a lower mortality rate from infectious diseases other than smallpox and tuberculosis^[2,3].

To do this, the authors examined blood samples from children before and after vaccination, looking at the production of cytokines by white blood cells when exposed to different components from viruses or bacteria. Cytokines are molecules produced by cells of the immune system that play a central role in regulating the immune response to infection.

They found that white blood cells produced fewer cytokines when exposed to pathogens after COVID-19 vaccination than before vaccination. This effect was seen in response to both bacterial, fungal, and viral components twenty-eight days after COVID-19 vaccination. Six months after vaccination, cytokine production in response to bacterial and fungal components was back to normal, however the cytokine production in response to viral components remained dampened. The authors thus concluded that “SARS-CoV-2 mRNA vaccination decreases inflammatory cytokine responses […] to heterologous bacterial, fungal and viral re-stimulation”.

The findings don’t imply that COVID-19 vaccination weakens the immune response of children

The study showed that the cytokine production profile changed after COVID-19 vaccination. But this doesn’t mean that vaccinated children are more susceptible to other diseases, as Berenson and others claimed. Science Feedback reached out to Berenson to ask what evidence he has in support of this claim; the review will be updated if additional information becomes available.

Science Feedback reached out to the study’s authors for comment. In response, the study’s authors forwarded to us via email a statement they published, refuting such claims:

“Our research does not provide any evidence to suggest that COVID-19 vaccines are harmful to the immune system of children or adults. In particular, it is incorrect to suggest that our study results show that COVID-19 vaccines ‘suppress the immune system’.”

They added:

“These cytokine responses are only one facet of the body’s combined immune response and we do not know how long they last. We did not investigate the clinical consequence of these changes, which could just as easily be beneficial (e.g., by reducing harmful inflammation) as undesirable.”

This means that the immune system is extremely complex and a change in the cytokine response to stimulation doesn’t necessarily translate into reduced protection against infection. In fact, it could even improve the immune system reaction against other infections. For instance, researchers hypothesized that lower secretion of some cytokines in children compared to adults could explain their lower risk of severe COVID-19^[4,5].

Angeline Rouers, a senior research fellow at the A*STAR Infectious Diseases Labs in Singapore, supported that idea in an email to Science Feedback, explaining that “Cytokines are only one part of the immune response—we can also count on cellular components, such as T cells and B cells, and humoral response thanks to antibody production”.

“Moreover, a moderate cytokine response could be beneficial to fight infection. In contrast, a phenomenon known as ‘cytokine storm’ is largely known to be linked with more severe outcomes and pathogenesis in infectious diseases,” she pointed out^[6].

The study’s design limits the significance of its conclusion

Although it provides interesting information, the study by Noé et al. has some limitations.

First, the study used a very small sample. Twenty-nine children participated in the study and only eight continued for the long-term follow-up at six months after vaccination. The study’s authors explained that the sample size was small because few parents agreed to remain in the study.

Small samples are very sensitive to statistical flukes. Furthermore, we expect the cytokine levels to naturally fluctuate around an average value. With a small sample size, the results could be influenced if even a few children had lower-than-expected cytokine production on the day of testing by chance and not because of the vaccination. A larger sample size would reduce the influence that chance has on the results. Because of the limited sample size, we must interpret the results from Noé et al. with caution.

Second, this is a purely in vitro study. This means that researchers conducted their experiments in test tubes in a controlled laboratory environment. In vitro experiments are an important part of scientific research, but they don’t fully represent the complexity of the human body.

This is why clinical studies that include people are necessary to draw reliable conclusions about what happens in humans. Although Berenson acknowledged this lack of clinical data in Noé et al., this didn’t deter him from making claims about a “damaged immune response” or “immune deficiency” in children.

Commenting on the study’s experimental design, Rouers explained that “this is a very common procedure in the lab but the results have to be interpreted carefully since they do not reflect real life and how our body will react in case of a real infection. No clinical study has been done here to demonstrate that children vaccinated with COVID-19 mRNA vaccine are more susceptible and/or experience more severe symptoms due to other infections.”

Conclusion

The study by Noé et al. showed that some immune system components in children reacted differently to pathogens other than SARS-CoV-2 after COVID-19 vaccination. This was an in vitro study with samples from a small number of children, which limits the significance of its conclusions. It doesn’t tell us whether vaccinated children would fare better or worse against other pathogens, and for how long. Clinical research on COVID-19 vaccines showed that they are safe for children and teenagers. The American Academy of Pediatricians recommends that children and teenagers aged six months and above get vaccinated against COVID-19.

The study by Noé et al., published in the journal Frontiers in Immunology, highlights the heterologous effect of BNT162b2 COVID-19 vaccine in children. Their results are interesting for the scientific community, showing that there is a change in cytokine production against other pathogens after a dose of COVID-19 mRNA vaccine in children. Unfortunately, the results of this study have been misinterpreted and led to several articles claiming wrongly that mRNA vaccines against COVID-19 damage the immune system of children and put them at risk of other infections.

The authors have already commented on this and clarified that their study does not aim and does not demonstrate any damage to the immune system in children after COVID-19 vaccination. The usage of the word “alters” by the authors probably brings the confusion to the public, but their study does not support the evidence of a persistent immune deficiency against other pathogens.

The article by Alex Berenson used the study by Noé et al. to claim that COVID-19 vaccines damage the immune response of children. He highlights the fact that “cytokines like interferon play a crucial role in the immune system, helping it attack viruses and other foreign invaders”, which is correct but incomplete. Cytokines are only one part of the immune response—we can also count on cellular components,such as T cells and B cells, and humoral response thanks to antibody production. Moreover, a moderate cytokine response could be beneficial to fight infection. In contrast, a phenomenon known as “cytokine storm” is largely known to be linked with more severe outcomes and pathogenesis in infectious diseases^[6].

The study by Noé et al. is well conducted and does not show discrepancy in the data but the public should take note that this is an in vitro study: cells have been isolated from the blood of vaccinated children and cultured in a plastic well with stimulants to observe how they react. This is a very common procedure in the lab but the results have to be interpreted carefully since they do not reflect real life and how our body will react in case of a real infection. No clinical study has been done here to demonstrate that children vaccinated with COVID-19 mRNA vaccine are more susceptible or experience more severe symptoms due to other infections.

The article by Berenson also claims “it appears that the mRNA shot caused a persistent immune deficiency in children”, which is an overinterpretation, since the study is only looking at 28 days after the second dose of vaccine for most of the cohort, and only eight samples have been analyzed six months after vaccination. There is thus no evidence of “persistent” change—and not deficiency!—of the immune response in this study.

Finally, it is well established that vaccination against COVID-19 is beneficial for children^[7]. The vaccination allowed us to limit the propagation of the virus. Despite the lower frequency of severe complications during SARS-CoV-2 infection in children compared to adults^[8], kids may still experience syndromes such as multisystem inflammatory syndrome in children (MIS-C)^[9] that can be significantly reduced by vaccination^[10].

REFERENCES

• 1 – Noé et al. (2023) BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists. Frontiers in Immunology.
• 2 – Sørup et al. (2011) Smallpox vaccination and all-cause infectious disease hospitalization: a Danish register-based cohort study. International Journal of Epidemiology.
• 3 – Zimmermann et al. (2018) Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis. Journal of Infectious Diseases.
• 4 – Rotulo & Palma (2023) Understanding COVID-19 in children: immune determinants and post-infection conditions. Pediatric Research.
• 5 – Steinman et al. (2020) Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics. PNAS.
• 6 – Teijaro et al. (2017) Cytokine storms in infectious diseases. Seminars in immunopathology.
• 7 – Borchering et al. (2022) Impact of SARS-CoV-2 vaccination of children ages 5–11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021–March 2022: a multi-model study. The Lancet Regional Health Americas.
• 8 – Salzberger et al. (2021) Epidemiology of SARS-CoV-2. Infection.
• 9 – Wittaker et al. (2020) Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA.
• 10 – Levy et al. Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France. JAMA.