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  • Alex Cloherty

Putting 'immunity debt' under the microscope

Tripledemic. Strain on hospitals. Immunity debt. These terms have been swirling around the news and social media in the last weeks as respiratory syncytial virus (RSV) cases surge above ‘normal’ seasonal levels. But let’s take a look at that third term, shall we? As an immunologist, the term ‘immunity debt’ was rather new to me, and therefore I wanted to put it under a metaphorical microscope.

‘Immunity debt’ is the hypothesis that ‘non-pharmaceutical interventions’ to control COVID-19 (e.g. social distancing and working from home) caused a subsequent decrease in immunity to a variety of microbes. This hypothesis suggests that all of the actions that we took over the last years to prevent SARS-CoV-2 from spreading also effectively stopped the spread of many other viruses and bacteria throughout the population, but that this is actually a negative thing. As a result of staying in and staying apart, this hypothesis claims that our immune systems have become soft and used to being coddled - meaning that now that we can go out and about again after a long period of pausing all social activities, we will only get hit harder with seasonal bugs like RSV.

Although I’d never heard the term ‘immunity debt’ before this year, I had heard vague references to such an idea. The idea of immunity debt is also connected with the relatively well-known hygiene hypothesis: the idea that regular exposure to things like hay and grass, unprocessed animal products, dirt, and other non-sterile things trains our immune systems in regards to what they should respond to, and how much they should respond. According to the hygiene hypothesis, such early and hearty training of the immune system leaves a kid with a nice balanced immune system that is equally developed in its ability to respond to all different kinds of threats - meaning that that same kid will be less likely to develop allergies, which are in essence an immune overreaction. This is a very interesting hypothesis to be sure, but that’s the thing - it is still a hypothesis. Just as is the concept of immune debt. It does sound logical, but it’s not really been proven to be the case. Therefore, it’s positively interesting to ponder, definitely exciting to debate, but possibly risky to put into practice.

Myself, I was rather sceptical from the first moment that I heard about the news stories touting immunity debt as the sole explanation for surging RSV cases, because in my opinion it seems like an over-simplified analysis. For one, there are different strains of RSV that can dominate at different times, just like different strains of influenza (or SARS-CoV-2 for that matter) circulate in different years. One study in the USA showed that the B strain of RSV was dominating in 2018-2019, but the A strain was dominating in 2019-2020. Similarly, in Argentina RSV A was dominant in 2019 and was replaced by RSV B in 2021. As for 2022… Well, I searched on Google, Google scholar, PubMed, the WHO’s website, the Dutch ministry of health website, Health Canada’s website, and the American Centers for Disease Control website, and I couldn’t find any information about exactly which RSV strain is circulating this year. The only mentions of both “RSV” and “strain” that I found were in news alerts that the high amount of RSV cases are putting strain on healthcare systems.

What I was wondering during my search was, could it be that kids were simply more exposed to RSV A pre-pandemic, followed by RSV B during the pandemic, and now a somewhat sudden re-circulation of RSV B is challenging young immune systems? I don’t have the answer to that - and please let me know if you find any information on exactly which type of RSV is circulating currently. But if that would be the case, that there is indeed a slightly different RSV strain going around this year, well, such an occurrence would be nothing new. Sudden switch-ups in the dominating circulating viral strain are regularly responsible for higher-than-normal severe flu cases, for instance. It’s an epidemiological certainty that viruses will change over time.

On that note, just like other viruses, the RSV virus can mutate from season to season. And indeed, RSV strains have been evolving over the course of the pandemic. For instance, a study in China reported that the RSV strains that they tracked in Shanghai before the COVID-19 pandemic were genetically similar to the strains observed in Europe. However, the RSV B strains that they analysed during an unseasonal upsurge of RSV infections during the summer of 2021 were rather different from European strains. This illustrates that viruses can evolve very rapidly, and shows that unseasonal peaks of viral disease can be caused by a multitude of reasons, as the authors write at the end of the paper: “The factors contributing to the ‘summer peak’ of RSV in the post-COVID-19 phase were complicated, possibly including relaxation of restriction measures, increased social activities of children, extensive respiratory virus testing to rule out COVID-19, and possible changes in the environmental resistance of RSV strains”. In other words, it’s complicated, and it’s an oversimplification to only point a finger at immunity debt when there are many possible other explanations.

But let’s stop for a moment, and assume that immunity debt does exist, and that it is the main underlying reason for surging RSV infections. How do we solve this problem then? The primary answer to that particular question, as far as I’ve gathered from my scan of the media is… Get infected.

Now that is a conclusion that I have some problems with.

According to this logic, it can be argued that we also have an immunity debt in regards to smallpox. By analogy, the only way to solve the smallpox immunity debt, then, would be to make sure that as many people as possible are infected with smallpox on a yearly basis. I, for one, would not be in favour of such a strategy. I am extremely pleased to be able to live a life without smallpox.

And that life without smallpox is possible thanks to, you guessed it, vaccinations. So yes, I think we are very much on the right track in including life-saving vaccines in any science-informed public health strategy. If we want to avoid the spread of deadly diseases, the safest and most effective strategy known to humankind is to vaccinate against those diseases when possible.

To conclude, it is too early to say if immunity debt is real, and if it is one of the many possible causes of the upsurge in RSV cases that we are seeing. But even if it is, for now my personal practical conclusions, based on all of the science that I’ve read, are 1) I’ll be awaiting Pfizer’s pending RSV vaccine with great excitement, and 2) I’ll continue wearing my face mask on public transport (without it my face is always cold these days, anyways). I know my immune system is well-trained by the vaccines that I carefully schedule for myself, and if I can easily avoid getting sick, and making other people sick… Well, why not?

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