You will likely remember that the Wild Bunch, a group of outlaws led by Butch Cassidy, had a Wyoming mountain pass hideout called the Hole in the Wall. It can be really difficult to corner and defeat adversaries that have hideouts that are hard to reach. The same is true of various illnesses in medicine.
The classic medical examples of the Hole in the Wall phenomenon come from cancer. There are medicines that are highly effective against certain cancers. Still, after a patient appears to be cured, the cancer returns because the cancerous cells have entered a biological hideout where they cannot be reached by the medicines. That is, all medications achieve different levels of potency in different tissues. A medicine that achieves high levels in the blood, for example, may not penetrate solid tumors or fatty tissues very well. And antibiotics that are highly effective in lung tissue may be useless in the treatment of abscesses. There are many similar examples.
The reason that I am reflecting on this phenomenon of biological hideouts is that we have seen the same phenomenon in viral infections. It is possible to have an undetectable HIV level in the blood and still find detectable virus in the testes, for instance. So, this phenomenon of COVID recrudescence after treatment with Paxlovid isn’t all that surprising. Although the mechanism by which SARS-CoV-2 manages to escape antiviral therapy is not yet well-understood, I wouldn’t be surprised if we soon learn that there are hideouts where Paxlovid does not achieve sufficient levels to eradicate the virus. Thus, after a time of apparent cure (negative COVID tests), the virus multiplies there and again becomes detectable in the host. I would expect that the host’s immune system would have time to respond and quell the re-immerging infection in some individuals and not in others.
Hideouts, whether for highwaymen, bacteria, cancer cells, or viruses are a challenge.