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Small-Scale Question Sunday for December 31, 2023

Do you have a dumb question that you're kind of embarrassed to ask in the main thread? Is there something you're just not sure about?

This is your opportunity to ask questions. No question too simple or too silly.

Culture war topics are accepted, and proposals for a better intro post are appreciated.

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I acknowledge that our understanding of the immune system remains pretty limited, but we are pretty certain that getting sick is bad for you

My understanding is not so much that getting sick is bad for you but rather that sickness occurs when your innate and specific immune systems are unable to stop/manage the replication of a given microorganism within the body without broader measures (fever, inflammation, production of mucus).

In terms of whether that is long-term bad, some sicknesses are indeed debilitating, and if one could achieve the same net outcome with less severe symptoms then it would clearly be preferable to do so. This is what happens with live accentuated vaccines in particular- a very mild illness (possibly subclinical) occurs that trains the specific immune system to recognise a feature of the attenuated pathogen common to the actual disease, resulting in reduced or eliminated illness when the actual disease is encountered.

I think the point is that this process occurs on a much broader scale on a daily basis as one travels through life. You are constantly exposed to microbes, and you can think of the body using mild or non- illness generating microbes of the same type as the training set for its response to novel (i.e. new to the body) pathogens. More data and more similar data= better response to a new pathogen.

The risk of actively trying to reduce illness by avoiding social contact and wearing a mask is that you are successful and your immune system "drifts" out of sync with the rest of the population. This is due to a reduced training set meaning that more pathogens are novel to the body.

If this occurs, then novel pathogens that would not harm the broader population due to previous exposures to them or related microbes still harm you because you have missed that exposure. The resulting illness will consequently be more severe because you have no cross-immunity, and so your immune system is effectively starting from scratch in its response.

You might object that the whole point is to avoid any airborne pathogen through masking and thus no risk of illness actually arises. However, a) you still have some social contact and thus disease vector and b) the countermeasures are only risk reduction not elimination. As your immune system drifts, then the range of potential pathogens increases as you lose cross-immunity. You therefore have the a lower absolute risk of being exposed to a given microbe, but the relative risk in the event of exposure is greater.

At the most extreme, uncontacted tribes have immune systems highly adapted to their limited social circle and environment: and no immunity against common circulating pathogens that generally cause mild illness such as influenza. This is not due to intrinsic immune differences between them and the rest of humanity, but rather a consequence of limited exposure.

Hope that explains why one might not wish to "mask up". I've not got into whether masks result in lower initial pathogen counts (and if so whether this is practically advantageous) or the broader effectiveness or social desirability of masks.

I do not expect that masking or isolation, even taken to an extreme, will cause any notable negative health effects due to your immune system getting "out of sync".

That might apply if you were being raised in a clean-room since birth, but as far as I'm aware, in situations such as an immigrant from the Global South going to the West, you don't see them suddenly falling sick because of all the novel pathogens circulating in a country several continents away. International travel at that range is not so common that I expect everything to become homogeneous when it comes to the short-scale evolution of pathogenic microbes. Note I am not claiming the opposite, it is both true and a trope that Western visitors to the Global South often catch stomach bugs because of exposure to pathogens that the locals are inured to, but that's more a factor of said pathogens being more common, be it because they flourish in tropical regions, or because of lax standards in food safety or water treatment.

I do not expect wearing a mask in public for even years on end to change anything, our innate immunity does a lot of the heavy lifting, the adaptive component, while not negligible, is hardly sufficient, as anyone going through flu season can tell you. We are also vaccinated for the worst diseases, and I'd expect maskers to be even more fastidious about getting their shots.

Uncontacted tribes do have differences in innate immunity. You can literally trace historical population exposure to diseases like the Bubonic Plague, Smallpox or Malaria through genetic adaptations. But someone in civilized society fastidious about masking is never going to be as vulnerable as them, once again unless they were raised in a clean room from birth. If there is a negative effect, it's too trivial to worry about.

On your comment on the differences in innate immunity in different human lineages, you're absolutely right and I was being imprecise in my wording. Mea culpa.

On the broader point, I think that you are potentially neglecting the common phenomenon of traveller's flu for the South to North traveller. People do get ill due to e.g. diffetences in circulating influenza strains. Agree that illness in the North to South traveller is more likely and severe due to the broader range and exposure to excitingly virulent pathogens.

You are of course right to say that the innate does a lot of the work, but for potential pathogens that can evade the initial response, then as you know a major factor in the severity of the illness (I.e length and how debiliating it is) is the existence of relevant B- or T- memory cells. My argument is that fewer relevant memory cells (etc) exist if you have experienced fewer relevant infections due to reduced exposure. Vaccines can close some but not all of the gap simply due to sheer range of potential pathogens.

Perhaps a relevant example would be a person from 1910 time travelling to 1925, at which point the Spanish Flu is still circulating. They would have a higher risk of dying from Spanish Flu than the average 1925 person because they do not have previous exposure to the strain itself, or to the various similar strains circulating post-1917 and generating relevant cross-reactions.

I think the only way masks work out for reducing severe illness long-term is if there is indeed a dose effect that results in exposure to the same pathogens but milder illness. If masks are so effective that one only gets ill vanishingly irregularly, then the risk of that occasional illness being severe are increased due to lack of relevant previous exposure. If masks are not effective at all such that one has a similar immune profile to the general population, then there is little point in wearing them.

I have never heard of Traveler's flu before, and as far as Google tells me, there's no clinically recognized condition by that name.

The closest I can find is this publication:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505480/

Methods: We conducted a PUBMED/MEDLINE search for a combination of the MeSH terms Influenza virus, travel, mass gathering, large scale events and cruise ship. In addition we gathered guidelines and recommendations from selected countries and regarding influenza prevention and management in travellers. By reviewing these search results in the light of published knowledge in the fields of influenza prevention and management, we present best practice advice for the prevention and management of influenza in travel medicine.

Results: Seasonal influenza is among the most prevalent infectious diseases in travellers. Known host-associated risk factors include extremes of age and being immune-compromised, while the most relevant environmental factors are associated with holiday cruises and mass gatherings.

I don't think this has much to do with traveling to a new place as much as it does with being crammed in tight spaces with poor ventilation with hundreds of others.

Similarly, if you travel to a new country during the flu season, you're at increased risk of catching it, but so are the locals. I am not aware of any literature claiming that new immigrants are at additional risk of catching flu and similar diseases, relative to the native population.

Masks vary greatly in terms of effectiveness, both from the specific type in question and proper use and adherence. But for a typical adult who begins masking in public, I do not expect that the the decreased exposure to pathogens will significantly impact their susceptibility to novel strains. In the case of the common cold or the flu, prior infection to a previous strain isn't protective for the next one that does the rounds, which is why flu vaccines are refreshed annual (and designed pre-emptively, based on models of what the next strain might be).

If someone masked and avoided the flu, for say, 2 years, I strongly doubt they are at any additional risk if they stop masking or catch the next one despite masking.

This is a different consideration from children, since I know that atopy is associated with insufficient exposure to a diverse array of microbes in childhood. Everything from peanut allergies to asthma can be mitigated by exposing them early and often. But for an adult, I do not expect it to make a difference.

Mind you, I don't disagree that wearing masks is largely pointless. Unless you're immunocompromised or are working with people who are, they are unlikely to help, unless maybe if you wear an N-95 on the plane and so on. What I disagree with is that they are meaningfully harmful on net to an average adult, which is a different question entirely from whether they provide benefits.

There are places, like China and Japan, where masking in public was common before the pandemic, and I have seen no claims that makes them more susceptible overall to respiratory illness when they do get it.

In the case of the common cold or the flu, prior infection to a previous strain isn't protective for the next one that does the rounds, which is why flu vaccines are refreshed annual (and designed pre-emptively, based on models of what the next strain might be).

If someone masked and avoided the flu, for say, 2 years, I strongly doubt they are at any additional risk if they stop masking or catch the next one despite masking.

I think I disagree with the statement that various types of flu/colds do not generate any immunity: they simply fail to generate sufficient immunity to avoid symptomatic infection, which is why the new strains are able to circulate in the fairst place.

Now you can reasonably disagree that this cross-reactivity actually matters in terms of disease length/prognosis if you're still not immune enough to avoid getting ill, and I'm not sure whether it has been tested empirically. But it makes intuitive sense at least, and the principle seems to be accepted e.g. in this 2009 paper looking at swine flu immunity in the general population https://www.pnas.org/doi/abs/10.1073/pnas.0911580106

Overall, seems like a hard thing to study. Would be interesting if someone did an East/West study on whether flu is actually worse in the East due to reduced exposure (noting that it might still be less prelevant on the net due to effective masking). I would fall back on the statement that either masks are effective and decrease your exposure to disease and therefore your immunity relative to the unmasked population, or ineffective and therefore pointless.

Yes, that's the "immune debt" hypothesis. It's a completely reasonable internally consistent hypothesis; it's not at all obvious that it's better to avoid infection entirely as opposed to hopefully getting minor infections that train the immune system while not being severe enough to do any lasting damage.

... but as far as I can tell, every vaguely reputable scientist with knowledge of the immune system or epidemiology thinks it is wrong and the odds don't work out that way.

To be clear, I'm merely claiming less exposure to pathogens is healthier. There are obviously costs to going out of your way to reduce your exposure to pathogens and the trade-off may not be worth it.

I'm not sure I share your views on whether immune debt is an unsupported position in the broader scientific community, but suspect that appealing to consensus may be unproductive.

Maybe the difference arises in the type of pathogen being discussed. A brief taxonomy could be the below:

  1. Rabies- no benefit to natural exposure as exposure is lethal. Vaccination/avoidance only means of reducing this.
  2. Cholera etc- natural exposure should be avoided due to high risk. Avoidance of causative agent possible.
  3. Influenza- high but limited number of strains. Some strains (e.g. Spanish Flu) lethal. Prognosis depends on strain, previous exposure, general immune strength.
  4. Colds etc- lots of disease causing agents. Prognosis typically mild or subclinical depending on prior exposure and general immune strength.

I agree that you avoid (1) and (2) if possible.

For (3), it depends on the costs and consequences. Through the veil of ignorance, I personally think we opt for as high an exposure as possible to the extent this is typically mild. This can be via vaccinations or general exposure: to the extent that lower cost options such as vaccines are available, they should be taken, and the equation may change as technology moves ( for example a universal flu vaccine would negate the benefits of natural exposure).

For (4) I think you just take the mild cost.

So in this view, avoiding some pathogens is healthier, but for others it increases the effects of related pathogens so it is not healthier on the net.