COVID Transmissions for 4-26-2022

Back in business; let's discuss pediatric vaccines and treatment...and remdesivir

Apr 26, 2022

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 869 days since the first documented human case of COVID-19. In 869, a Viking invasion of Britain is in full swing, led by the sons of Ragnar Lothbrok. Ivar the Boneless and his brother Ubba extract protection money from the Kingdom of Mercia, and in the same year use the “Great Heathen Army” that they lead to invade and devastate the kingdom of East Anglia, capturing and eventually brutally killing its king, today known as Edmund the Martyr. Look, it was a pretty violent, horrible time to be alive, but the names of the characters involved are pretty incredible.

I’ve been away from you for quite some time, and I think I owe you an explanation. My computer died suddenly and was in need of repair. My only other option to write to you would have been by work computer, and my employer owns the work I do on that machine. So I waited until repairs could be effected—and in the end, I chose to get a new machine, in hopes that this would mean I don’t find myself in the same situation again sooner than later.

Today we’re going to talk about pediatric vaccine and treatment options. We are also going to revisit the status of remdesivir.

Bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

Revisiting remdesivir

File:Remdesivir Potentialkarte4.png — A cartoon of the chemical structure of remdesivir. Created by the Wikimedia Commons user OChemski, found here: https://commons.wikimedia.org/wiki/File:Remdesivir_Potentialkarte4.png

It has been quite a while since I wrote about remdesivir, one of the first new antivirals that made headlines for activity against SARS-CoV-2. Remdesivir had a mild effect in an early clinical trial, reducing hospital stay durations in at-risk hospitalized patients. At the time, this looked like the best we could do, but over time it became clear that the effect did not bear out as well in real-world settings as it did in that particular clinical trial.

From that, many thought that remdesivir simply didn’t work. However, a study published towards the end of last year looked at remdesivir in non-hospitalized at-risk patients (not so different a group as are candidates for PAXLOVID,1 the Pfizer-made antiviral). That study is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757570/

In this study, the risk of progression to hospitalization or death was reduced by 87% with the administration of remdesivir. Rates of adverse events were comparable with remdesivir vs placebo, and of the list of specific adverse events, none stand out as particularly caused by remdesivir, at least in my opinion.

The study only has about 500 patients, but I think this is is interesting evidence that supports not totally dismissing remdesivir in highly at-risk people. The only issue is that remdesivir is still an intravenous drug, and other options like molnupiravir and PAXLOVID are administered orally.

That said, molnupiravir has raised some eyebrows because it might be mutagenic—something I am only concerned about in growing children or pregnant people, frankly—and PAXLOVID has a lot of potential drug-drug interactions. So there may be a population of people who need a third option, and I think that remdesivir could be a good candidate there. There are, of course, also some antibody cocktail options that work well. We are accumulating a deep bench of tools to fight COVID-19 in those rare cases where vaccination isn’t enough.

Speaking of the special populations that might turn to remdesivir, I’m going to use a subheading for once! There was a recent remdesivir approval that caught my eye:

Remdesivir expanded to use in people 4 weeks of age and older in the US

The FDA yesterday expanded the remdesivir EUA for possible use in people as young as 4 weeks of age with COVID-19. This makes it the first and only treatment option available for young children with severe COVID-19 or who are at risk of progressing to severe disease: https://www.fiercepharma.com/pharma/fda-expands-approval-gileads-veklury-providing-children-covid-treatment-option

This is very important news, and is actually why I chose to revisit remdesivir today. the expansion of this EUA means that we now have the option to do more than just take our chances when children get COVID-19—we have an actual drug option that we would expect to meaningfully impact outcomes, and that can be given to children without deviating from labeling instructions. I would call this a substantial win. It’s no alternative to vaccination, but it will reduce the chances of kids dying of this disease. I’m all for that.

Moderna to submit pediatric vaccine application by end of month, but there’s drama

Moderna announced recently that it is preparing a submission package to the FDA with its relatively-positive pediatric vaccine results: https://www.fiercepharma.com/pharma/moderna-seeks-fda-nod-covid-19-vaccine-children-under-6-starts-delayed-filing-older-kids

They are filing separately for the 6-and-younger group as well as the 6 to 11 group. The 6-11 group was a filing delayed due to concern over myocarditis, but now that the Pfizer mRNA vaccine has had essentially no cases of that adverse event in kids 5-11, it seems Moderna feels more confident about their chances with the FDA in that group too.

The 6-and-younger group are of course the big news, though, since there is still no vaccine available for them. This is the biggest gap in our potential vaccine coverage, and remains one of the biggest blindspots for otherwise well-meaning people who wish to say that we should just all get vaccinated and move on with our lives. Many of us—particularly those with very young children—cannot just get vaccinated and move on.

Getting a vaccine on the market for young children would cover one unmet need, here.

Unfortunately, comments by important health officials such as Tony Fauci have indicated that review of this vaccine may be delayed so that the Moderna and Pfizer vaccines can be evaluated simultaneously.

I have to say I do not understand this decision at all. Moderna’s vaccine is ready for evaluation right now. There are children who could get the vaccine before the summer season, with trips to camp and family travel, and thus be protected, if it were evaluated now.

Administration officials say that they think it will be confusing in some way to have different dosing regimens for children available—with Pfizer likely providing 3 doses while Moderna appears effective with 2 doses—and that they want to evaluate both vaccines at the same time partly to resolve these concerns. But this in itself does not make sense to me. The Johnson and Johnson vaccine requires fewer doses, and I don’t think anyone found that to be terribly confusing. In fact I think some people saw it as a selling point for that vaccine.

I think it is pretty easy for people to understand the differences here. The Pfizer vaccine uses more doses but at a lower amount of RNA per dose. The Moderna vaccine has more RNA (but it’s not a strictly linear comparison) given in fewer doses—for the time being. Boosters may be necessary, of course.

But regardless, I think most people can understand that difference and will be able to make a choice as to whether their child should have one vaccine or the other. If they can’t, they should talk to their doctors, who can certainly understand it. This is not a very complex issue.

The explanation for the delay is baffling enough that members of Congress from the Biden administration’s own party are looking for answers: https://news.yahoo.com/congress-wants-fda-explain-reported-212539596.html

I could speculate as to some other reasons for this delay, but none are very flattering and I don’t have enough direct information to really justify it. I think we should still be treating COVID-19 like an emergency, and getting a vaccine available for children is a top priority in addressing that emergency. I don’t want the review delayed now that the data are here. I also want to see those data discussed in a fully public forum, by experts, as part of that review process.

Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.

Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.

No corrections since last issue.

What am I doing to cope with the pandemic? This:

New computer

As I mentioned, I was unable to write to you for a short period because my 8 year-old computer ran into some trouble. It was fully repaired with no-cost software interventions, but the process took over a week and I ultimately realized that the next time this happens, the repair might not be nearly as easy to implement.

So, we traded it in towards a brand new iMac and here I am with a new computer (excepting computers issued to me by employers) for the first time since graduate school. You can look forward to COVID Transmissions coming your way from this machine for the foreseeable future.

So far so good. I remain pretty much entirely brand-loyal to Apple, if only because I have Apple devices that were manufactured during Steve Jobs’s lifetime that still function. In fact, at least one was made in the 20th century. I don’t use them much, but it’s impressive how long they’ve lasted. Building things that I can rely on is a pretty sure way to get my business.

Reader Brock asked:

This is not related to the topic of this particular post, but here's something I've been wondering.
At the beginning of the pandemic, the received wisdom was that SARS-CoV-2 was primarily transmitted by droplets, hence the emphasis on hand washing and staying six feet apart. Now that we know that SARS-CoV-2 is airborne, should we be re-thinking the received wisdom about transmission of other common respiratory viruses, such as influenza and the various common-cold viruses?

I don’t feel very confident in my knowledge of all common cold viruses, nor even specifically common cold coronaviruses, but I gave what answer I could here:

I think that it has become clear that our understanding of these transmission events is more limited than we might have thought, yes. However! I do not think we are very wrong about influenza transmission, because we have good animal models for such transmission. Close contact does seem to matter quite a lot for that disease, which I think bears out in its reproductive coefficient that hovers just over 1 most of the time. Viruses that we know to spread effectively through airborne aerosols have much higher reproductive coefficients.
A question arises with regard to common cold coronaviruses, though. Have they been spreading primarily through the air all this time, and we miss a large number of asymptomatic or subclinical cases, so we don't know? I am not expert enough on these particular viruses to comment. Perhaps someone does already have this knowledge; perhaps it should be investigated further. Getting the grant money to do that might be a challenge, though. Science is eternally underfunded, and as the pandemic gets less politically important I don't think we're going to do the smart thing as a species and increase research funding into these basic questions. If we did, we might be better prepared for the next pandemic. But we had a warning shot with SARS-CoV-1 in 2003, and we clearly didn't do enough to prepare then. So I don't see us doing much more, now.

You might have some questions or comments! Join the conversation, and what you say will impact what I talk about in the next issue. You can also email me if you have a comment that you don’t want to share with the whole group, or if you are unable to comment due to a paywall.

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