It’s Not For Me To Say

In an op-ed at Bloomberg infectious disease authorities Arturo Casadevall and Liise-anne Pirofski try to explain why it’s hard to predict who will live and who will die after contracting COVID-19:

Among individuals in the same risk group — the same age, say — differences in infection outcome can result from five different variables outside their control.

The first of these is microbial dosage or inoculum, the number of viral particles that cause infection. Small numbers of viral particles are more likely to be contained effectively by the body’s defenses. Then, infection may cause no symptoms or only mild disease. In contrast, a large number of particles can lead to increased viral growth, overwhelming the immune system and causing more severe disease.

Genetics may also influence susceptibility to severe infection. Viruses often gain access to host cells via surface proteins, which vary in presence and nature from person to person. Someone with no such surface proteins may be resistant to infection. In the case of HIV, for example, some people lack the receptors needed for viral infection and are not susceptible to the virus.

A third variable that influences infection outcome is the route by which a virus enters the body. It’s possible that virus inhaled in the form of aerosolized droplets triggers different immune defenses than does virus acquired by touching contaminated surfaces and then touching one’s face. The nose and the lung differ in local defenses, so the route of infection could significantly affect the outcome.

The fourth variable is the strength of the coronavirus itself. Viruses differ in virulence — their capacity to damage host tissues or immunity — even when they are all the same species. This is why flu seasons vary in severity from year to year. The varieties of a virus such as coronavirus differ depending on small genetic characteristics and how these affect the interaction with human hosts. As the coronavirus spreads from person to person, it may undergo unique changes in its genetic structure that enhance or attenuate its capacity to do harm. Strains that are more virulent could lead to more severe disease.

Finally, people’s immune status — especially their history of prior infectious diseases — crucially determines how they respond to a new infection. The immune system remembers previous encounters with microbes, and that affects how it fights and responds to new ones. In the case of dengue, infection with one type of the virus can make the individual more susceptible to infection with a different type of the same virus. In other situations, a recent infection with a virus can affect susceptibility to an unrelated new infection. For example, having had the flu before coronavirus infection could change the course of Covid-19 disease in unpredictable ways. When a person’s immune system has no memory of an infectious agent, it may be unable to rapidly respond, and this may allow the invader to escape detection, giving it more time to cause damage.

And then there’s the interactions among these factors.

It’s not entirely clear to me why that explanation is actually better than attributing it Providence or fate. They’re about equally predictive.

6 comments… add one
  • steve Link

    Each of these can be investigated. Providence not so much. Right now we are mostly clueless. I will say that we are seeing more people now who are younger and without significant co morbidities than we originally expected ending up on vents.


  • Guarneri Link

    I suspect that over time all those issues and potential interactions among them will be studied and understood. The science will win in the end. Until then, they are just intellectual musings almost useless clinically.

  • CuriousOnlooker Link

    Shorter revision of the article.

    There are factors you do not control, partially control, and in control of that determine how serious the illness.

    Factors you do not control — age, sex, blood type.
    Factors you control — living a healthy lifestyle, practice good hygiene
    Factors you partially control — your general health

    There is uncertainty how important each of these factors are.

    Question — Is there concern or evidence that survivors of serious / critical illness may have long lasting damage (like we have seen with SARs). Or is it still too recent to make conclusions?

  • PD Shaw Link

    @CuriousOnlooker, that looks like a good list, though I would be certain to specifically include the genetics angle to “factors you do not control” since it was mentioned. I don’t like the suggestion in the piece though that one’s DNA may impart immunity, which is doubtful, but a lot of the variations btw/ peoples today presumably originate from things like pandemics that they survived. Blood type may be an inexact proxy.

    As to your question, I think the issue with potential long-term respiratory damage is under-discussed. Probably because death is a simpler concept to define and appreciate.

  • steve Link

    “Or is it still too recent to make conclusions?”

    Sort of too soon. We know that a certain percentage of people will have long term issues just from having a long term intubation (Vocal cord damage , tracheal damage, pneumothorax) but I dont think we know yet if this is going to act like ARDS where we know there are long term pulmonary or other organ system issues.

    One of the experimental drugs we are using causes very severe constipation, to the point that there have been deaths reported. (They obstruct and perf) Some of those people will need bowel resections to save their lives and then will have lifetime complications from that. Just one example we are finding.


  • CuriousOnlooker Link

    Thanks Steve. Keep up the good work.

    I am afraid long term damage will be a sleeper issue.

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