(You may well know this, but posting for the benefit of other readers.)
Nirmatrelvir, which is one of two drugs that make up Paxlovid, reduces long covid risk by about 30% for medically diagnosed infections (which means it was serious enough to actually get you to the doctor). An optimist might hope the other drug (which is in the same class, although most commonly used as an adjuvant) is also useful and round this to 50%.
...nirmatrelvir, which is one of the two drugs packaged together to make Paxlovid. I’m going to be an optimistic and assume the second drug was included for good reasons, which make this study underrepresent the usefulness of Paxlovid.
Wikipedia: Nirmatrelvir/ritonavir explains that ritonavir (the other drug) is commonly understood to be playing its role by inhibiting your body’s breaking down nirmatrelvir, leading to higher serum concentrations at trough:
Nirmatrelvir is a SARS-CoV-2 main protease inhibitor while ritonavir is a HIV-1 protease inhibitor and strong CYP3A inhibitor. Nirmatrelvir is responsible for the antiviral activity of the medication against SARS-CoV-2 while ritonavir works by inhibiting the metabolism of nirmatrelvir and thereby strengthening its activity.
Wikipedia: Ritonavir adds some detail on this mechanism and adds that its helpful role in antiretroviral therapy for HIV is also commonly understood to be by inhibiting CYP3A4 (the human enzyme that breaks down many protease inhibitors like nirmatrelvir and ART cocktail components).
I don’t have a head-to-head study of nirmatrelvir vs nirmatrelvir+ritonavir close at hand, but ritonavir is responsible for many-to-most of Paxlovid’s drug-drug interactions, which are commercially negative for the manufacturer (Pfizer). Given that there’s no real reason to add those side effects if the ritonavir weren’t significantly helping, it seems pretty reasonable to update towards “ritonavir improves the efficacy of nirmatrelvir on at least one commercially-useful axis”. That axis is likely not specific efficacy against Long Covid (which I think is not particularly relevant to Pfizer’s approval path or commercialization strategy), though you might hypothesize that it would correlate.
(You may well know this, but posting for the benefit of other readers.)
Wikipedia: Nirmatrelvir/ritonavir explains that ritonavir (the other drug) is commonly understood to be playing its role by inhibiting your body’s breaking down nirmatrelvir, leading to higher serum concentrations at trough:
Wikipedia: Ritonavir adds some detail on this mechanism and adds that its helpful role in antiretroviral therapy for HIV is also commonly understood to be by inhibiting CYP3A4 (the human enzyme that breaks down many protease inhibitors like nirmatrelvir and ART cocktail components).
I don’t have a head-to-head study of nirmatrelvir vs nirmatrelvir+ritonavir close at hand, but ritonavir is responsible for many-to-most of Paxlovid’s drug-drug interactions, which are commercially negative for the manufacturer (Pfizer). Given that there’s no real reason to add those side effects if the ritonavir weren’t significantly helping, it seems pretty reasonable to update towards “ritonavir improves the efficacy of nirmatrelvir on at least one commercially-useful axis”. That axis is likely not specific efficacy against Long Covid (which I think is not particularly relevant to Pfizer’s approval path or commercialization strategy), though you might hypothesize that it would correlate.