Comment by rossdavidh | Hacker News Reader

Comment by rossdavidh | Hacker News Reader

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From near the end:

"Actually, I think the same thing about Paxlovid treatment. In that case, the worry is the rise of mutated forms of the coronavirus that are also Paxlovid-resistant. That’s more or less inevitable, but we should not accelerate it by handing out the drug to populations where it won’t make much difference."

We have a real mismatch of incentives here. In order for Paxlovid to remain effective, it would need to not be used very often (so that a resistance to it doesn't constitute a big advantage for that variant). This is ok, if we only give it to elderly or otherwise high-risk populations. But how high-risk?

Many individuals want to consider themselves "high-risk" in order to get a prescription, but would be better off if everybody else besides themselves is not considered high-risk. It's a classic Prisoner's Dilemma.

Add to that the fact that the makers of Paxlovid (or Molnupiravir, for that matter) have an incentive to want it to be prescribed as much as possible, and we have both individuals and corporations pressuring the system to do exactly what it should not do, which is hand out the anti-viral to way more people than it should.

This cannot be fixed without changing the system (e.g. paying drug developers by a bounty system rather than with a patent).

I'm not sure that prisoners dilemma is the right framing of this problem.

First, there's value in decreasing the viral load of ALL patients regardless of risk, as viral load is likely proportionate to risk of onward transmission. If it decreases onward transmission, then the math would likely favor its use in all cases, since exponential spread gets costly fast.

Second, we continue to focus on hospitalizations and deaths with increasingly poor data and with no focus on disability. Treatment may decrease risk of long covid in non-"high risk" patients, which itself may be beneficial.

Third, while we should expect paxlovid-resistant variants to pop up, the fact that we prescribe it about 4x the rate of molnupiravir and don't see nearly that level mutation should be somewhat comforting. It seems equally plausible that a new "long branch" lineage would pop up with resistance irrespective of evolutionary pressure from paxlovid prescriptions. If that's the case, it'd be a shame to ration its use to only have it go bad anyway (this is basically what we saw happen with all of our monoclonal antibodies).

Fourth, this entire conversation should be less focused on who we deem worthy of one of our last remaining treatments, and more focused on how we're allowing a very quickly mutating virus to spread virtually unchecked and with basically no investment in any further treatment or prevention. None of us need to be prisoners here if we were continuing to invest in new treatments, better vaccines, improved air filtration and ventilation, and paid sick leave.

Tragedy of the commons seems a more appropriate analogy than prisoner's dilemma. This is "basically" (ignoring all the scientific differences) the same problem as antibiotic resistance, and the paradox where if everyone takes antibiotics, selection pressure leads to dominance of the bacteria most resistant to those antibiotics. And indeed, this situation is frequently framed as an example of "tragedy of the commons." [0]

[0] https://www.cambridge.org/core/journals/journal-of-law-medic...

I would agree that "tragedy of the commons" could work. But the basic feature of "prisoner's dilemma" that I was referring to is that we're all better off if we all avoid taking antivirals or antibiotics when we are not high-risk, but each individual is better off if they defect and everyone else does not.

SARS-CoV-2 has already spread everywhere. The majority of people worldwide have been infected at least once. Exponential spread is no longer a thing. Transmission will continue forever at lower levels, just like other endemic human coronaviruses such as HCoV-OC43. At this point, giving Paxlovid to a few more COVID-19 patients is unlikely to significantly reduce the spread of SARS-CoV-2.

There may be good reasons to prescribe Paxlovid more widely. It's just that reducing transmission probably isn't one of those reasons.

If you re-read what you have written and try to detach your thinking from the various polemics of how bad lockdown is...

"Exponential spread is no longer a thing." -- Clearly wrong. Every time a +ve person breathes out on a bus, in a pub, at the office, exponential spread is occurring. The only difference is that many of those people had a recent immune event (a booster or recent infection) and suppress it immediately, or if it has been some time, they get a COVID infection and their T cell response kicks into action and suppresses it. People can have multiple infections per year. People with weakened immune systems will still get very sick.

Because it is still propagating with new variants there is still the potential for significant widespread waves of illness. It might be very important to be able to issue Paxlovid or something similar to everyone who is sick, or even give it a prophylaxis to e.g. cancer patients.

In the literal sense, exponential spread _of Covid-19_ is clearly no longer a good description in the US (or many other countries). It may describe the spread of new variants, but the impact on most people of getting the latest variant of covid-19 is about like the impact of getting the latest variant of influenza (which can kill you, but normally does not). The number of people with covid-19 is not going exponentially up, as it once was, it is now coming in waves that are probably never going to reach the peak of the initial Omicron.

Now, literally speaking, every new variant of covid-19, influenza, or any cold virus is obviously going to be exponential (and half of the time, exponential decay). But the population is no longer "immunologically naive", in western countries.

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