COVID Transmissions for 2-11-2021
Another potentially effective treatment for COVID-19
Good morning and welcome to COVID Transmissions.
It has been 451 days since the first documented human case of COVID-19. That’s one day for every Fahrenheit degree of temperature it takes to ignite paper.
Today we discuss a Phase II trial of an apparently effective COVID-19 treatment, and also new CDC guidance on mask-wearing.
And then a reader comment!
As usual, bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Peg-interferon lambda may help treat COVID-19
A Phase 2 trial whose results were released yesterday caught my eye, partly because of the drug in question—and also partly because I work with the senior author in my day job, in a very different disease area.
The trial examined the use of something called peg-interferon lambda in COVID-19 patients, and can be found here: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30566-X/fulltext
In this trial, patients (whose disease was not severe enough to require hospital treatment) were given either a single injection of peg-interferon lamba or of placebo. Patients who received the peg-interferon lambda saw their number of SARS-CoV-2 genome copies drop 263 times as far by Day 7 compared with patients who received placebo. They were also 4 times as likely to have no detectable virus at Day 7 by comparison with patients who received placebo. Also, when they compared patients based on their baseline number of detectable virus genomes, they say that patients with a higher “viral load” by this measure were more likely to benefit from peg-interferon lambda than from placebo. Specifically, the higher the baseline viral load, the more benefit patients seemed to obtain from the drug, as shown here:
The result is fairly straightforward: the bigger the amount of virus genomes that patients had at baseline in their samples, the less likely they were to have become negative by Day 7. However, while patients who received placebo were a lot less likely to be negative at Day 7, patients who were given peg-interferon lambda did not see this same drop. The drug seems to substantially increase the changes that the virus will be cleared, and that increase is resilient even to very high baseline viral load.
Now, this is very cool, but I have to point out there were only 60 patients in this study.
Still, I find it super interesting. My PhD is about virus-host interactions related to what’s called the interferon response. There are many types of interferons, but they are broadly classed into Types I, II, and III. Subtypes of these get Greek-letter names. Interferon lambda is a type III interferon; interferon alpha and beta, which are close to what I studied, are type I interferons.
Interferons are very important in immune responses, with type I interferons being especially important in activating early antiviral responses. For a very long time, the only effective treatment for hepatitis C virus was artificial type I interferon treatment. Like the interferon lambda used in this study, these interferons were modified with the addition of polyethylene glycol (PEG) to help stabilize them. Hence, “peg-interferon lambda.” Unfortunately, the type I interferons, at least, can be very inflammatory and they can produce wide-ranging and undesirable adverse effects.
Early on in the COVID-19 pandemic, type I interferons were explored as a potential was to treat the disease, but they didn’t seem to have enough of an effect at safe doses. That’s not too surprising; type I interferons tend to be most relevant very early during infection, in the first day or few days.
Type III interferon, on the other hand, is a more recent discovery and is thought to be involved in longer-term responses to virus infection. As such, it might be a good candidate for a drug to treat COVID-19 and other virus-based diseases—and in this trial, that appears to have been true.
By showing that peg-interferon lambda can have longer-term effects to control COVID-19, this study validates years of research into type III interferon, demonstrating that it can act to have impacts at later points during a virus infection. I am excited to see how this treatment may perform in a Phase III trial.
CDC now says double-masking is more protective than single-masking
As we’ve discussed before, it now appears that wearing two masks is genuinely better than one, but only in certain conditions and for certain types of mask. They found, though, that two masks reduced escape of simulated aerosol virus by about 95% in an experimental setup involving dummies. You can read more details from NPR: https://www.npr.org/sections/coronavirus-live-updates/2021/02/10/966313710/cdc-now-recommends-double-masking-for-more-protection-against-the-coronavirus
These types of experiments aren’t always perfect, but they’re a pretty good model.
That said, there are some other points to take away. First, the research underlying this showed that any mouth-and-nose covering mask is better than no mask, and also that other measures that make masks fit tightly to the face can be as effective as double-masking. Essentially, the takeaway about double masks is that they help to improve the fit of the mask to the face. Other techniques (see the article, it has a lot of details!) also can improve the fit. The better the fit, the better the seal and thus the better the mask(s) are at protecting the wearer and others.
They do mention, though, that double-masking is not as effective with some mask types, like disposable masks, as it may not improve the fit in those cases.
What am I doing to cope with the pandemic? This:
200 pounds
Yes, this is kind of a silly stereotype, but I hit a personal record at the gym last night by bench-pressing 200 pounds, and it’s nice to be able to achieve something like that that I’ve worked for over the course of 2020 and into 2021. This has been a tough time, so part of coping is celebrating things no matter how cliché or silly they may appear to be.
What makes this an even bigger milestone for me is that a year ago, I weighed almost 230 pounds. I’m now around 200, and able to lift my own body weight. Putting in the work has really changed things for me.
Reader David Rendsburg left the following comment:
At what point will we know more about whether vaccinated people can still carry the virus and infect others? With millions of people already vaccinated shouldn't we have decent data on that already?
To some degree, the jury is still out on this question, but last week I shared some results that convinced me there’s a substantial reduction in the ability to be infected, with at least one of the vaccines. In case you missed that issue, it’s linked in my reply:
So far the best data we have on this are from the AstraZeneca vaccine, which was covered in the 2-3-2021 issue: https://covidtransmissions.substack.com/p/covid-transmissions-for-2-3-2021
To see the effects at a population level, we are going to need extremely high uptake in one large geographic region with good epidemiological surveillance. No country is quite where we need to be for that yet, but the closest candidate is Israel.
You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.
Join the conversation, and what you say will impact what I talk about in the next issue.
Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.
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.
See you all next time.
Always,
JS
That figure of 263 times greater reduction in viral load daily seemed implausibly high. If baseline reduction is 1%, then with interferon, it would be over 100% reduction, or to zero, in one day. If baseline reduction is not as high as 1%, placebo patients would need many months to recover. I'm also dubious about measuring daily reduction in viral genome count, because the underlying assumption there is that this number is constant, and it shouldn't be. As the immune system responds, it would start fairly low, but the rate would naturally increase as B-cells start pouring out antibodies and T-killer cells start multiplying.
I then searched the Lancet paper, and the number 263 does not appear in it. Typo?
The mask recommendations are missing a key thing: ratings for non-medical masks. I can buy any of a hundred "medical style" masks that look like surgical masks, but without actual regulated testing, I have no way to know their actual filtration ability, and without different testing I have no way to know how likely they are to fit tightly. Creating a rating system for this purpose would be one of the best things the FDA (or WHO) could do, in my opinion.