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.