Thread by @ENirenberg

Against my better judgment, I'd like to talk about this term "immunity debt" because the way that this discourse is taking life of its own is a problem to say the least. 🧵

Foremost, the issue here is that the term is being used imprecisely- people are writing definitions to fit their preferred ideologies. The paper the term stems from doesn't ever formally define it, but we can work out what it's trying to say:
sciencedirect.com/science/articl…

Basically, a lack of exposure to specific pathogens is proposed to have resulted in reduced immunity to those pathogens, and so if the measures taken to reduce circulation of those pathogens is lifted, a resurgence of those pathogens is expected to occur. Indeed, it has.

That said, I very much don't like this term. I don't seek to prosecute the authors who coined it, as it furthermore appears that English may not be their first language, but the term seems to connote that to be healthy it is necessary to be sick. That doesn't make sense.

In particular, I am seeing the term be misused to reflect some perverse form of the hygiene hypothesis (more properly the Old Friends hypothesis- pnas.org/doi/10.1073/pn….) wherein this lack of exposure to pathogens has now harmed our immune system- that is nonsense.

The world did not suddenly become sterile during the period of pandemic precautions. For example, take a look at the incidence of rhinoviruses throughout the pandemic period of precautions in Seattle:
seattleflu.org/pathogens
Clearly they didn't go away!

But, even if they had, we would still be far from sterile because we are all colonized by entire ecosystems of microbes that provide stimulation to the immune system:
nature.com/articles/s4142…

Humans aren't comparable to germ-free mice!

Non-pharmaceutical interventions enacted during the pandemic played an important role in saving lives, particularly before vaccines. For example:
link.springer.com/article/10.100…

They weren't a mistake.

Furthermore, many of them are worth continuing even outside the circumstances of a respiratory virus pandemic. For instance, improved ventilation and humidification are broadly useful for many infectious diseases, and masking in high risk settings is also appropriate.

Yet another party to this conversation argues that the current situation is the result of immunological deficiency induced by COVID. I would like to state this unambiguously: there is no high quality evidence to support that this is a real phenomenon.

COVID is not HIV, COVID is not measles. It does not readily infect T cells (embopress.org/doi/full/10.15…). It does not cause T cell exhaustion (nature.com/articles/s4159…). Reduced counts of these cells during infections are almost always from them leaving blood and going to tissue.

The one possible exception here would be those who have particularly severe cases of COVID-19, where it has been seen that sometimes CD8 T cells might have trouble bouncing back:
onlinelibrary.wiley.com/doi/10.1111/al…
And limited subsets of long COVID patients:
medrxiv.org/content/10.110…

I would also emphasize that this does not appear to be from SARS-CoV-2 infecting the cells in question in these rare cases but because of hyperinflammation during the acute phase (thelancet.com/journals/ebiom…, atsjournals.org/doi/10.1164/rc…) or in the case of long COVID...

new onset autoimmune disease, or persistence of antigen or virus past the period of acute infection:
nature.com/articles/s4159…

However, neither of these states are common enough among the relevant demographics (i.e. young children) to explain current epidemiological trends. Also, not to belabor the obvious but COVID-19 is obviously not a disease you want and should be avoided to the extent possible...

but in particular should be avoided in the context of a state lacking any prior immunity against it (theinsight.org/p/novelty-mean…), something that is really obvious if you compare COVID-19 outcomes as the pandemic progresses and in vaccinated vs. unvaccinated.

Now, it would be useful if we had some historical precedent for the current situation- and we in fact do. Polio flourishes by transmission through the fecal-oral route, and before we had proper sanitation, exposure to polio was ubiquitous in infancy.

Because of maternal antibodies (transplacental and breastfeeding), the incidence of paralytic polio was generally very rare. But then hygiene improved, and polio exposure was delayed- maternal antibodies faded. And the incidence of paralytic disease rose:
ncbi.nlm.nih.gov/pmc/articles/P….

Another example is rubella: early rubella elimination strategies focused on vaccinating infants because they are the natural reservoir for the virus (even though the reason for the vaccine is infection of the fetus in utero).

As uptake of the vaccine rose, there was indeed decreased circulation of rubella- but those rare rubella cases which did occur happened to pregnant individuals with lower antibody titers to the virus and thus more limited ability to protect their fetuses.
academic.oup.com/cid/article/43…

This is actually known as a post-honeymoon epidemic: because incidence of a disease drops, people aren't exposed and don't develop immunity- and so when the disease appears again, you have more susceptible people and it resurges.
link.springer.com/article/10.216…

Anyway, the question becomes: what do we do about this? Do we just let people get sick to keep up high levels of immunity?
That feels a bit like using pregnancy as birth control.

Do we keep up non-pharmaceutical interventions forever? Depending on the specific intervention...

that could be very difficult in practice.

The answer is: we need vaccines. We need an RSV vaccine, we need a (better) influenza vaccine- we have unmet needs for a number of vaccines for pathogens that sicken us.

Vaccines avoid this problem because they grant immunity so that even when the pathogen resurges, incidence is more constrained and outcomes are consistently better. The good news is that effective RSV vaccines seem to be forthcoming- maybe in time for next season.

In the interim, get your COVID vaccines, get your flu vaccines, wear a well-fitted high-quality mask, stick to well-ventilated and humidified areas, and be especially cautious around high risk groups (including children).

Also as for what to call this because immunity debt seems to be such a problematic term- I don't know. I do like this option though:

https://twitter.com/butts_4_jesus/status/1599115693516988416?s=20&t=2O40UMJB6_O_V1YGAOivvw

Point of clarification as I made a faux pas (h/t @zoonotic1) - the rubella situation is probably not best described as a post-honeymoon epidemic.

For details on post-honeymoon epidemics, this seems like a nice guide:
ncbi.nlm.nih.gov/pmc/articles/P…