Saturday, October 10, 2020

Remdesivir, a target for loons, pseudoscientists, and conspiracy theorists

At this moment, Czechia is by far the most Covid-active country in the world, a fact that is caused by Czechs' not being afraid of this disease now, despite the efforts of the prime minister, minister of health, and a few others who would like to reignite the fear. We still had concerts, ice-hockey matches with thousands of fans etc. last night, the life is continuing normally. Culture, sports, and fun will be banned for two weeks from next Monday; after the totally free July and August, we basically added another month of almost complete freedom in which it was already clear that the disease was quickly growing.

It's nothing pleasant. This infection beating rates of positive tests that were seen anywhere in the world, ever, brings us first tangible negative stories. We know the first people around us who suffer from Covid and/or whose relatives and friends are not only positive but may be at risk; whose girlfriends lost their smell, and so on. We're afraid of the outcomes of their struggles.

Being the #8 power in the world (in absolute numbers; relatively, it's some 800 new cases per million inhabitants and per day) gives the Czech doctors some extra right to claim that they're experts. With those 8600 cases a day, we're still getting just some ~25-30 deaths a day in average in recent days.

The number of overlooked Covid-positive people is undoubtedly high. It has to be high simply because the percentage of the positive tests was 32% on Friday! It's very clear that aside from the 25k tested people where it's 32%, there have to be at least 200k more which you could pick where it would be 20% etc. Just imagine the terrified nations declaring 6 weeks of the national lockdown when 0.1% of their tests were positive. We are at 32% and it still seems rather likely that we will avoid a lockdown, an option that is considered extremely unpopular and claimed to be deeply harmful for the economy.

If you want to know, the deaths are a bit above 900 now, growing ~30 a day. Hospitalizations are at ~1900, growing ~150 per day. Serious cases are above ~400, growing by 10-50 a day. 800 mild hospitalized patients will be moved to hotels, a smart move, especially because hotels are surely under-utilized now. While only ~400 ICU-like beds are used by Covid patients now, we have some ~800 available – the system is ready for another tripling of the serious Covid cases. Claims about the cracking Czech healthcare system are exaggerated (a euphemism for "complete lies").

The death-to-cases ratios is much lower than it was in spring, pretty much proving that the disease is comparable to flu in average. Maybe a less severe variant of the virus has spread; maybe people are getting lower doses now; and maybe it's because of the treatment. In Czechia, doctors use all kinds of treatments, obviously oxygen, mechanical ventillation, and favipiravir, convalescent plasma, isoprinosine, corticosteroids, and... especially remdesivir.

I've been promoting the increasing usage of remdesivir since March 3rd. Of course, we in Czechia are more motivated to do so because it's our drug. Here is the Time Magazine explanation how the antiviral drug works. Tomáš Cihlář, a Czech guy in California, is the antiviral vice-president of Gilead Sciences that makes the drug.

As the mechanism makes clear, the drug is really a variation of the most important drug that mankind uses for HIV, Viread (Tenofovir disoproxil). It's a part of most anti-AIDS protocols. That compound was originally created by Mr Antonín Holý, a legendary Czech chemist. The Czech institute is still getting royalties every year that exceed the revenue of the Prague International Airport – and due to the troubles of the airline industry, that gap is likely to grow. And Tomáš Cihlář is basically one of the junior collaborators trained by Holý who made a variation of it – which could have been effective against hepatitis C and Ebola but it accidentally turned out to work for Covid.

In spring, it was believed that the drug was optimal for serious Covid cases. After all, it's expensive and costs $2,000 to $3,000 per U.S. patient. The Czech prices are much lower, results of negotiations between Gilead and the government. At any rate, it seems weird to give such an expensive drug for something that looks like flu. But the situation is changing and remdesivir has been shown to be maximally effective when it's given to the mild patients who just start to ask for oxygen. So the current Czech rules actually imply that Donald Trump was an optimum recipient of the drug, despite (partly politically motivated) claims to the contrary. A few days ago, the number was 870 or 890 of the Czech patients who have already gotten remdesivir.

The first Czech serious Covid patient back in March, fat gypsy driver Robert Markovič, was saved but there were doubts whether remdesivir was crucial. However, in recent weeks, we had many more examples of patients where the positive role of remdesivir looked self-evident. One of them was the member of the European Parliament Jiří Pospíšil who got Covid and bacterial pneumonia and was feeling miserable. They gave him remdesivir and indeed, he was released from the hospital 5 days later (perhaps right after the last 5th dose). The rate of his improvement seemed like a self-evident signal by itself.

You know, I am amazed by the people who claim that remdesivir is a superstition, fraud, or something like that. I had to ban a bunch of these people on Twitter because they may get really obnoxious. This drug isn't a far-fetched speculative homeopathy drug. It's something that's been given to some 1,000 Czech patients and in a really big fraction of them, the positive effect looks obvious to the naked eye. The Czech doctors are rational and really competent. If it had no effect, they would have noticed.

And indeed, in recent days, studies showing that the drug works started to flood the literature. Two days ago, a NEJM double-blind study concluded that the drug shortens the recovery time from 15 days (placebo) to 10 days (remdesivir) in average. On the very same day, a similarly encouraging result was released about remdesivir administered to pregnant women. They did fine and had no serious side effect caused by the drug.

Czechia is just a few percent of the current market for the drug, however. There have been tens of thousands of patients and a significant fraction of them was "self-evidently improved" by the drug. The idea that this is all a mirage is a conspiracy theory comparable to those that tell us that not only there was never any moonlanding; but you can't see the illuminated Earth from the Moon LOL! ;-)

As a short-distance thinker, of course I find the in-vitro tests of remdesivir to be the primary evidence. The replication of the virus clearly decrease when you add remdesivir into a testtube. Aside from the theory that makes sense, that's the (almost) hard science behind the drug. But this (almost) hard science doesn't print a guide for doctors how they should use the drug. And indeed, how this drug should be used is an extra layer of the expertise, a much softer science, something like arts or a craft. But doctors aren't pure scientists. They are a mixture of scientists and very practical people or artists. In arts and crafts, the experience matters and so does the doctors' experience.

So it took months to decide that a 5-day-long remdesivir treatment is generally better than a 10-day-long treatment (something I would guess right away, and maybe an even more concentrated one might be even better). And it took some time to figure out that you should really try to give it to some milder cases than those that were "instinctively" picked in March. But it works and can save lots of lives, probably a clear majority of those that would otherwise be lost.

Remdesivir is expensive but easy to produce and there should be doses for everyone; doses for 2 million patients should be out by the end of 2020. On top of that, Gilead Sciences has tested an inhalation version of the drug and as far as the monkeys' health was concerned, it seemed as effective as the intravenous injection (the side effects should be largely avoided). [Note that nitric oxide could end up being a very simple competitor, however.] To summarize, I think that for a few months, remdesivir was already in the stage of "a drug that clearly makes a difference" and whose usage is just being optimized to be even better. The views that it doesn't help at all are really becoming equivalent to the moonlanding conspiracy theories because drugs that don't work (and I think that HCQ doesn't work) have already been rather clearly seen to be useless, the signal-to-noise ratio has simply become high enough to distinguish drugs that work from the rest.

The other drugs, favipiravir, convalescent plasma, isoprinosine, corticosteroids, may be cheaper and may work even better than remdesivir, it is a part of the game. Trump took Regeneron's REGN, a mixture of two artificial antibodies. I think that antibodies are the "cleanest" solution which is probably even more natural than something like remdesivir. It is possible that this Regeneron (produced from stem cells, something that is a natural reason for attacking Trump's pro-life credentials) made the main difference for Trump. But when he said that he felt not just fine but better than 20 years ago, it was almost certainly due to the steroids he received because steroids do cause the states of euphoria. I think that a macho guy like Trump is even more dependent or sensitive on steroids! ;-)

Czechia will go through another month of this elevated Covid activity. Many of us will be afraid, some of us will have to be saddened. A vaccine may arrive and the minister of health has declared his intention to strip you of the face mask duties if you are vaccinated (it should apply to all other restrictions; and to the immune Covid alumni, too). This is a sensible incentive to get vaccinated. But the current fatality rate due to Covid is so much smaller than in spring (also due to remdesivir) that we should simply go through this unpleasant experience at full speed. The Czech doctors' petition against the hysteria and restrictions has over 64,000 signatures now. I am disappointed (and surprised) that our government doesn't just accept this fact – that the penetration comparable to herd immunity is unavoidable – and doesn't try to make everyone sure that it can really manage it. The new minister is obviously a reason why it's so. He's fighting against the wind mills (while he can only brag about the fastest acceleration of Covid in Czechia ever) in order to masturbate his colonel's ego. The sensible singer-model-Ken (from Barbie) was so much better for this job! Ken was in a constant contact with the real doctors who made it very clear to him that while there was suddenly more work for them, they managed to deal with it just fine.

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