The Best Way To Protect Children From COVID? Let Them Get Sick

Cross-immunity Is Especially A Thing For Children

Readers may recall how last month a study¹ appeared in the Lancet establishing that natural immunity is the best defense against COVID-19.

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Moreover, the study found not just that natural immunity was “as good as” the inoculations, but that it was arguably better (emphasis mine).

Although protection from re-infection from all variants wanes over time, our analysis of the available data suggests that the level of protection afforded by previous infection is at least as high, if not higher than that provided by two-dose vaccination using high-quality mRNA vaccines (Moderna and Pfizer-BioNTech)

Now the “experts” are surprised to discover that not only is natural immunity still a thing, but so is cross-immunity, and especially so for children.

Some scientists have also suggested that children may have a higher level of existing immunity to COVID compared with adults. In particular, this immunity is thought to come from memory T cells (immune cells that help your body remember invading germs and destroy them) generated by common colds – some of which are caused by coronaviruses.

In other words, when children are exposed to the pantheon of infectious respiratory pathogens that produce the symptoms of Influenza-Like Illness, infection by some viruses helps build immunity against other viruses.

The utility of cross-immunity against COVID-19 in children was the focus of a study² recently released in the Proceedings of the National Academy of Sciences (PNAS), documenting that cross-immunity does in fact exist among young children, and while the effect wanes it does carry over into adulthood.

Our results provide evidence that functional pre-existing SARS-CoV-2-reactive memory CD4⁺ T cells are elicited in early childhood and linked to seroconversion with the seasonal coronavirus OC43 but not many other viral infections. Compared to other viruses, the high OC43 seroprevalence at age two indicates that memory responses to coronaviruses develop at a young age. The distinct age-dependent profiles of the responding T cells suggest that cross-reactive T cells can contribute to the different clinical outcomes of COVID-19 in children and the elderly. The present results provide important advances regarding antigen-specific memory CD4⁺ T cell development and maturation, which can help guide future vaccine and therapeutic interventions relating to specificity, function, and phenotype of memory T cell responses throughout the human life span.

Thus, as one is exposed to the generally milder coronoviruses—229E, NL63, OC43, and HKU1—not only does one gain measures of immunity against the virus itself, but also against more severe pathogens such as the SARS-CoV-2 virus. This is particularly true for children.

The study was done specifically to confirm anecdotal observations of apparent cross-immunity—i.e., these results are not at all a fluke.

Early in the pandemic, scientists observed the presence of memory T cells able to recognise SARS-CoV-2 in people who had never been exposed to the virus. Such cells are often called cross-reactive T cells, as they stem from past infections due to pathogens other than SARS-CoV-2. Research has suggested these cells may provide some protection against COVID, and even enhance responses to COVID vaccines.

Moreover, the earlier referenced research³ noted the impact cross-immunity could have vaccine efficacy.

We evaluated the available evidence assessing the role of CCC and SARS-CoV-2 immune cross-reactivity in SARS-CoV-2 infections and vaccine outcomes and provide a detailed table of experimentally verified cross-reactive T and B cell epitopes of SARS-CoV-2 (Supplementary Table 1). Our analysis suggests that pre-existing cross-reactive T cells may provide some protection from COVID-19, whereas there are no data that convincingly show a role of cross-reactive antibodies in COVID-19 clinical outcomes. Similarly, CCC cross-reactive CD4⁺ T cells that are detectable before vaccination may enhance responses to both mRNA-based and viral vector-based vaccines^62,100,101, whereas pre-existing cross-reactive antibody responses are enhanced by vaccination but do not themselves enhance overall vaccine antibodies titres. Despite evidence showing that cross-reactive T cells may be detrimental to the outcome of secondary infections in other virus families and that some unconventional^23,24,25 or low-avidity conventional T cell²⁶ populations may be associated with severe disease, to date there is little evidence suggesting a role for pre-existing cross-reactive T cells in exacerbating COVID-19.

Long-time readers may recall that prior COVID infection had also been found to improve immune system response to the mRNA inoculations.

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The study also found that natural immunity is highly impactful even among vaccinated patients.

Individuals with vs without prevaccination COVID-19 diagnosis had a 56% reduced risk for a breakthrough infection (AIRR, 0.44; 95% CI, 0.40-0.48).

While study authors gloss over this with their “academicspeak” verbiage, a “prevaccination COVID-19 diagnosis” only arises from prior infection, leading to natural immunity.

This research amplifies and confirms that earlier result. Time and again natural immunity simply works better than the mRNA inoculations.

Nor is this the first time the phenomenon of cross-immunity been identified with respect to COVID-19. As early as June of 2020—well before the mRNA inoculations were even being tested—research⁴ identified the mitigating effects of prior coronavirus infection in the body’s response to the SARS-CoV-2 virus.

Anderson et al used convalescent SARS sera to neutralize SARS-CoV-2 [42], demonstrating cross-neutralization of SARS-CoV-2 by neutralizing antibodies produced against SARS-CoV. Importantly, these neutralizing antibodies persisted for 9–17 years [42], further demonstrating long term immunity against SARS-CoV. Intriguingly, the neutralizing antibodies against the N protein of the two viruses was indistinguishable, suggesting of cross reactivity of antibodies against viral antigens [42].

It was even speculated that prevalence of other coronavirus infections—especially from sarbecoviruses and other SARS-like pathogens—played a role in reducing COVID severity among certain populations.

It thus seems obvious that there is a high degree of cross-reactivity between T and B cell epitopes of SARS-CoV-2 and other SARS-like viruses [41], which is also observed between antibodies produced against the relevant viral structural proteins [43]. Perhaps the comparative lack of serious cases of COVID-19 in locations where SARS-like infections have been prevalent is due to partial immunity conferred from cross reactivity of B and T cell epitopes and antibodies. To assess this hypothesis B and T cells epitopes and antibodies against SARS like viruses need to be assessed in convalescent COVID-19 patients with mild, moderate, and severe disease. Finally, longevity of SARS-CoV-2 antibodies need to be assessed to attain a better understanding of protective immunity and vaccine development.

Cross-immunity is thus a fundamental building block of overall effective immune system response to a pathogen—the degree to which pathogens are similar allows the immune system to utilize the mechanisms established for fighting off one pathogen to fight off similar pathogens.

Unsurprisingly, research⁵ has even shown that cross-immunity is naturally a two-way street—i.e., SARS-CoV-2 antibodies inform immune system response to other coronaviruses.

We then quantified antibody responses against the spike protein of OC43, which is an endemic coronavirus that causes common colds in humans. All patients had high levels of preexisting antibody titers against OC43, but SARS-CoV-2 vaccination increased antibody titers against this endemic coronavirus in most unexposed (including immunosuppressed) participants (22 of 29, 76%) (Figure 1, J–M), consistent with earlier studies (3). Prior to vaccination, antibody responses to OC43 tended to be higher in individuals who were previously exposed to SARS-CoV-2 (Figure 1M).

Thus, COVID-19 endows the immune system with a measure of enhanced response to other coronaviruses.

We next assessed whether cross-reactive antibodies could also be detected during a natural SARS-CoV-2 infection. We compared antibody responses in plasma from RT-PCR⁺, symptomatic patients with mild to severe COVID-19 as well as in healthy control plasma harvested before 2019 (Figure 2A. As expected (4), individuals with COVID-19 had higher levels of SARS-CoV-2 spike–specific antibodies (Figure 2B), as well as SARS-CoV-1 spike–specific (Figure 2C) and OC43-specific (Figure 2D) antibodies, relative to control individuals. We also measured antibody levels against the SARS-CoV-2 nucleocapsid protein for these 2 groups and found them to be significantly higher in patients with COVID-19 (Figure 2E). We did not observe any increase in influenza-specific antibodies in the COVID-19 cohort (Figure 2F). These data demonstrate that patients with COVID-19 develop cross-reactive antibody responses that recognize other coronaviruses.

Paradoxically, illness becomes a crucial element in the body’s ability to fend off illness—our immune systems function best when exposed to a variety of pathogens.

What is most noteworthy of this latest bit of research confirming that immunological naivete makes COVID-19 worse for children is that it is part of a substantial preexisting body of research identifying the beneficial effects of cross-immunity with particular reference to the SARS-CoV-2 virus.

At every turn, there has been research establishing that exposure to pathogens is the body’s best way for building up defenses to pathogens.

Note that I am saying “pathogens”, and not “spike proteins”.

While the antibodies induced by the mRNA inoculations may impact immune system response for other coronaviruses, prior research has also shown that exposure to pathogens is essential for eliciting whatever immune system response the mRNA inoculations impart. The immune system does best when allowed to develop responses to the whole virus, the whole pathogen, not merely a pre-determined bit of the protein coat.

Thus the best way to protect children from the worst effects of the most virulent infectious respiratory pathogens is to let them be exposed to milder related pathogens. Arm their developing immune systems by allowing the development of defenses against mild pathogens which will aid in warding off the more virulent pathogens.

Want healthy children? Let them get sick. Even “The Science™” now admits this works to ward off the more severe symptoms of Influenza-Like Illnesses.

1. Stein, C., et al. “Past SARS-CoV-2 Infection Protection against Re-Infection: A Systematic Review and Meta-Analysis.” The Lancet, 2023, https://doi.org/10.1016/S0140-6736(22)02465-5.

2. Marion, H., et al. “Functional SARS-CoV-2 Cross-Reactive CD4+ T Cells Established in Early Childhood Decline with Age.” Proceedings of the National Academy of Sciences (PNAS), 2023, https://doi.org/10.1073/pnas.2220320120.

3. Murray, S. M., et al. “The Impact of Pre-Existing Cross-Reactive Immunity on SARS-CoV-2 Infection and Vaccine Responses.” Nature Reviews Immunology , 2022, https://doi.org/10.1038/s41577-022-00809-x.

4. Yaqinuddin, Ahmed. “Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities.” Medical hypotheses vol. 144 (2020): 110049. doi:10.1016/j.mehy.2020.110049

5. Dangi, Tanushree et al. “Cross-protective immunity following coronavirus vaccination and coronavirus infection.” The Journal of clinical investigation vol. 131,24 (2021): e151969. doi:10.1172/JCI151969