Comments by "Theodore Shulman" (@ColonelFredPuntridge) on "Paxlovid, evidence base?" video.

  1. The argument that we should test the Paxlovid on patients who have been immunized (either by vaccination or by infection and natural immune-response), is good. By all means, test it on them! BUT it's reasonable to assume, until large tests are complete, that Paxlovid will benefit immunized patients in the same way it benefits those who have not been immunized. I'll explain why: Paxlovid is a combination of two medications. One of the two is Ritonovir, which doesn't do much by itself, but is useful for prolonging the lifetime of other protease-inhibitors. You can think of Ritonovir as like the linemen on a football team whose purpose is blocking the other team, to protect the guy who has the ball from being tackled by them. The other drug in Paxlovid is Nirmatrelvir, which is like the guy who has the ball. It inhibits the virus' protease enzymes which are essential to make the proteins it needs in order to control the host cell. Without those protease enzymes, the virus can't do its bad viral thing to you. The point here is, both these effects - the Nirmatrelvir inhibiting the virus' essential protease enzymes, plus the Ritonovir preventing the host from removing the Nirmatrelvir - both these effects are completely separate from antibodies and what antibodies do. In fact, as far as anyone knows, they are separate from the entire immune system. They inhibit the viral protease enzymes in the presence of antibodies, and they inhibit the viral protease enzymes in the absence of antibodies. Given what we know about how well they work for patients who have not been immunized, and given that their mechanisms of action have nothing to do with immunity or antibodies, it's reasonable to predict that they will also work well to protect patients who HAVE been immunized. This is not proof - of course, only big tests on previously-immunized patients would prove the benefit in those patients. But it IS a good reason to provide the Paxlovid unless and until large studies or surveys prove that it DOESN'T help those patients. The fact that Paxlovid has such great results on patients who have not been immunized, plus the fact that the mechanism of action is independent of antibodies, shifts the burden of proof to the skeptics, at least largely.
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  2.  @christopherrobinson7541  Yes, but remember, the benefit of Paxlovid is NOT that it stops the virus from entering the cell. I don't think it does stop that. What it stops is this: the virus mostly doesn't have separate genes for its proteins; it has one long stretch of genetic information (RNA) which codes for all the proteins. The virus enters the cell, releases the viral RNA, and the cell produces one big proto-protein - one long chain of amino acids, whose sequence includes all the viral proteins, strung together in one long chain, and then that chain gets cleaved, or chopped up by a protease enzyme, into the specific proteins the virus needs. The nirmatrelvir in the Paxlovid stops the "chopping up" process. This happens after, and independently from, the virus entering the cell.
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