COVID Transmissions for 3-8-2021
Dexamethasone: still effective!
Good morning and welcome to COVID Transmissions.
It has been 476 days since the first documented human case of COVID-19. To continue my historical theme of late, this one is a big one. 476 marked the “official” beginning of the medieval period, and the fall of the Western Roman Empire. The Germanic warleader Odoacer, tired of not being paid for mercenary services for the Western Roman Empire, led a revolt in Italy. This revolt culminated with the deposition of a Roman Imperial usurper. Emperor Zeno, the Eastern Emperor, who had problems of his own, refused to take up the Western throne for himself. Perhaps harkening to the Greek philosopher who shared his name, Zeno decided he preferred a divided empire. He recognized Odoacer as a Roman patrician and solidified Odoacer’s position as the King of Italy. This, and other recognitions of Germanic kingdoms’ authority by Zeno in 476, formalized and finalized the abandonment of the Western Empire by the Eastern Empire. At least until later, when they tried to get it back.
Today in present times, we are perhaps entering a period where COVID-19’s grip on the world will begin to recede.
The headlines today discuss new results from the RECOVERY trial for dexamethasone as well as a discussion of how a pandemic can impact pharmaceutical regulatory efforts.
As usual, bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Dexamethasone still quite effective in COVID-19
The New England Journal of Medicine published additional results from the RECOVERY trial, which is a massive trial of various COVID-19 therapeutics. We covered some of their results last week, with regard to IL-6 receptor antagonists. This study focuses on the corticosteroid dexamethasone, one of the first drugs shown to lower deaths in patients with severe COVID-19.
In approximately 6400 hospitalized patients, randomized 1:2 to dexamethasone vs standard of care, dexamethasone showed an approximate 17% reduction in risk of death during the 28-day period after randomization. This is good news, but the most striking effect was seen in those patients who were on mechanical ventilation, with a 36% reduction in risk of death over a 28-day period. Risk reduction was 18% in patients who were receiving supplemental oxygen but not mechanical ventilation. In patients who were not receiving either of these forms of respiratory support, there was no apparent effect on risk of death.
The study is here: https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
Keep in mind this is an open-label study, but it’s also not the first study to show an effect for this drug. I’m confident that for patients who are at pretty serious risk of death due to severity of their disease, dexamethasone represents a good therapeutic option.
COVID-19 regulatory backlog in the US
Sometimes, I like to get really wonky. I’ve been thinking a lot lately about the impact of a pandemic on pharmaceutical regulators—since I work in pharma, and for a company that had a product turned down for approval this year (with the option to resubmit), it has been on my mind.
Around the world, the COVID-19 pandemic has had a pretty strong impact on drug development. Clinical trials have had to suspend enrollment in many cases, to ensure that hospital bed space that is needed for COVID-19 patients is not being taken up by study patients. Patients have put off enrolling in studies, in other cases. And then, there is the massive burden of response that has been placed on worldwide regulatory agencies.
The FDA in the US is no exception. I have been impressed by their ability to review hundreds of new products for COVID-19, but it has come at some amount of cost.
One thing that has suffered is regulatory inspections of drug production facilities. The Government Accountability Office recently reported to Congress that more than 1,000 drug inspections by the FDA planned in 2020 could not be completed. CIDRAP has the story here: https://www.cidrap.umn.edu/news-perspective/2021/03/gao-spotlights-fdas-covid-related-drug-inspection-backlog
A lot of good details are present in that story, but what stands out for me most is that this represents an example of how a pandemic can strain the overall healthcare system in any country. Drug inspections are important. They keep the manufacturing process honest and they keep patients safe. If it’s dangerous for inspectors to do their work because of a pandemic, problems start to creep into the system. Hopefully these problems will not have wide-ranging effects, but it’s another on a list of many things to think about.
What am I doing to cope with the pandemic? This:
Finishing the Annals of the Western Shore
I mentioned recently that I was reading Voices, the second book in Ursula K Le Guin’s Annals of the Western Shore series. It was a good read, and I still think worth your time. That said, I started reading it because I wanted to get to the third book in the series, Powers, and I spent hours this weekend reading that. I’m not quite done yet, but it has been an incredible ride.
This book is Le Guin at her best. Something she has a talent for is using a protagonist’s failures, whether by luck or by their own limitations, as a means of utterly changing the setting in which she’s writing to show us something else of the world through the lens of her viewpoint character. In other words, we spend part of the book learning the arcane rules of the society where the character started, and then some catastrophe forces them to flee, with nothing, to a new adjacent society. There they must learn all sorts of new rules, until again some catastrophe forces the next move. In this, Le Guin shows us her vast capacity for sociological exploration through the eyes of a well-drawn character, while also creating a plot that is full of gripping twists and turns. This is mastery that many writers can only aspire to, and it’s a privilege to be able to read it.
Last issue, I posed the following question:
Question for you all: This newsletter is soon to outlive its peak usefulness. While COVID-19 isn’t over, I do expect that it will begin to be less important in our daily lives in the next 2-4 months. Given that, I am considering the future of this newsletter and how it will play out.
When I started this newsletter, I had no idea how long it would take to get to this point. I wasn’t sure I would still be doing this 7 months later—and I had no idea how many relationships it would build. Those of you who have reached out to me regularly to ask questions or just to talk about the pandemic have become a bright spot in a dark time for me. I’ve heard that many of you have similar feelings about this newsletter.
So I’d like to pose to you: when the pandemic ends, should COVID Transmissions end? I could envision continuing to write a regular newsletter that covers a wider set of topics in virology, though perhaps not at a daily frequency.
I’ve created a poll here to collect responses: https://forms.gle/kF5Mu1eJxyix7uGg8
I’m interested in what you all think.
I got a large number of responses (the form anonymizes them), as well as some signed comments. So far, overwhelmingly, there is clear interest in a continued communication of some kind. It is likely that I would expand the newsletter to cover more of the world of viruses and disease, but reduce the frequency, as we come out of the pandemic. This might include a name change.
I’m still interested in seeing responses, though.
Carl Fink also left a comment I wanted to respond to:
Why does Australia want the (not very effective) AZ vaccine in the first place? Wait 2 months and they can order the far better, far more convenient Janssen vaccine.
I think this is a terrible study for various reasons. I'd be interested in your opinion.
https://www.washingtonpost.com/world/2021/03/04/coronavirus-overweight-global-report/
Note: I'd rather go Yoji Kondo(https://en.wikipedia.org/wiki/Yoji_Kondo) than Marie. Still miss him.
Here’s my reply:
I agree with you, that obesity study sounds woefully confounded. It doesn't consider that more developed countries tend to have both better healthcare surveillance as well as more obesity, and it also doesn't consider that the US is a huge outlier in terms of death counts.
I don't think I would characterize the AZ vaccine as "not very effective." Remember that it's hard to cross-compare these vaccines with no head-to-head trials, and as far as I know all of them crashed rates of severe disease and death.
Yoji Kondo is not someone I was familiar with but I'm very impressed to learn of any other scientist who has also authored science fiction works. I see that he also used a pen name. I'll have to learn more about him.
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.
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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