COVID Transmissions for 10-29-2021
An off-patent antidepressant that can keep COVID-19 patients out of the hospital
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 712 days since the first documented human case of COVID-19. In 712, the Umayyad Caliphate continued an invasion of Iberia (modern-day Spain) that began in 711. 18,000 troops enter the peninsula from North Africa and conduct a drawn-out siege of Seville.
Today I want to discuss good news about two oral therapy options for COVID-19, both of which will thankfully be available cheaply in certain circumstances.
Then I also want to talk about disingenuous attempts by US politicians to undermine scientists and the scientific process. I try to avoid politics in my science, but when politicians force science into the political arena, it puts us all in danger and I can’t stay silent.
Also, a reader comment about child vaccination—and infection.
Have a great weekend!
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Antidepressant shows promise as anti-COVID treatment
A study of fluvoxamine, an off-patent antidepressant, in the treatment of COVID-19 recent read out in Lancet Global Health: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext
This study is part of a wider trial looking at a variety of products (including ivermectin!) in the treatment of COVID-19: https://clinicaltrials.gov/ct2/show/NCT04727424
The study of fluvoxamine was asking whether this drug could reduce the number of COVID-19 patients who end up in the hospital in a selected high-risk adult population—that was the primary efficacy endpoint. With 1500 patients, this is a sizable trial to look at that effect.
Compared to placebo, the risk of hospitalization was reduced by 32% with fluvoxamine treatment. One third of the patients who might have been hospitalized were kept out of the hospital through this simple, inexpensive intervention.
Based on this analysis—which wasn’t even the final analysis planned for the trial—it was determined that there was a 99.8% chance that fluvoxamine is superior to placebo for keeping high-risk patients with COVID-19 out of the hospital. This passed the superiority threshold of 97.6%, and the efficacy portion of the trial has been stopped because the benefit is obvious. This is typical practice; it is not ethical to continue to randomize patients to placebo when you have evidence that your active treatment obviously works.
The trial wasn’t really large enough to assess differences in deaths, and out of 1497 patients, 42 died across both arms. There was a numerical difference between the groups that wasn’t statistically significant, so I’m not going to make a big deal out of it.
In terms of safety, this is a drug that already has an acceptable safety profile in humans when taken for months or years as an antidepressant. These patients took it for 10 days, and there were no notable safety events compared with placebo.
This is great news, and adds another oral option to keep people with COVID-19 out of hospitals and recovering at home. Also, importantly, this drug is available in generic form, so it means potentially replacing one third of expensive hospital stays with an inexpensive medication. That’s good news for patients, and for stressed healthcare systems around the world.
Merck licenses molnupiravir to UN-backed MPP for free to help treat COVID-19 around the world
Remember the oral antiviral molnupiravir, that I wrote about several issues ago? If not, go here:
Molnupiravir adds another line of defense in the fight against COVID-19, but one problem with new drugs is that they are often prohibitively expensive around the world, particularly in developing countries that need them most. Molnupiravir is meant to keep patients out of hospitals so they can recover on their own, relieving burdens on the healthcare system. This matters in the US, but it matters even more in countries that don’t have advanced healthcare systems.
There are many countries where patients only go to the hospital to die. In those countries, a drug that keeps you out of the hospital is a drug that saves your life.
Likewise, there are other countries where extremely limited facilities lack surge capacity, and even slightly reducing the burden on the healthcare system can have a huge impact on who survives COVID-19.
The bottom line is that if these countries can get molnupiravir, it stands to really help their populations. Except, brand new drugs aren’t cheap when they’re under patent. It costs money to develop them, and companies want to make that money back.
A lot of the time, that’s where the story ends. Except, yesterday, Merck decided to add a new chapter to the story for molnupiravir, by providing a royalty-free license to a UN-backed nonprofit, Medicines Patent Pool, to manufacture the drug. This is going to mean doses of the product will be available cheaply in countries that would never have been able to afford it otherwise. Merck loses nothing by doing this, because again, these markets could never have bought their drug in the first place. Meanwhile, this compassionate gift saves lives. It’s one of those moments when I’m reminded of the good that can be done through the pharmaceutical business. Here’s a New York Times story on the deal: https://www.nytimes.com/2021/10/27/health/covid-pill-access-molnupiravir.html
NIH, NIAID, and Dr. Anthony Fauci smeared for perfectly sensible research
I normally try to avoid political items in this newsletter, to the extent that I can, but there is one issue where I will talk politics: attacks on the conduct of science and on scientists. These things endanger us all, and I can’t remain silent while people who work hard to protect humanity are libeled by politicians with selfish agendas.
Today I want to talk to you about something that has been bubbling in the background, or perhaps right out in the open in more politically conservative circles—attempts to discredit the US National Institutes of Health (NIH), the National Institute for Allergy and Infectious Disease (NIAID), and Dr. Anthony Fauci (or “Tony” as pretty much every virologist calls him).
There are two specific smears that I want to call attention to today.
The first is this: There have been claims that these entities supported what is known as gain-of-function research in Wuhan, China before the pandemic. These claims are false, as I discussed in a recent issue, but even if they were true, “gain-of-function” research is often vital to our understanding of human disease. Conducted in safe conditions, such research can provide us with the ability to predict what nature is going to do next, and maybe prevent pandemics before they start. Whatever mutational experiment you can imagine, it’s important to realize that nature is already trying it, somewhere. To avoid such research means, essentially, to force ourselves to be constantly reactive to emerging diseases, rather than being able to proactively fight them.
Don’t get me wrong, of course—there are irresponsible ways to do any type of research, and nothing should be done without oversight and safety procedures, but the smearing of this type of research is not coming from that type of constructive criticism. It’s coming from a place of ignorance. This Nature News article tries to shed some light on gain of function work and I think is a really valuable resource for anyone interested in the topic: https://www.nature.com/articles/d41586-021-02903-x
The second is one that reminds me of the time Sarah Palin tried to cause controversy over fruit fly research. She was using one study as an example of government waste, but she was dead wrong. Fruit flies are used for many things in science—fruit fly research is directly connected to such incredible feats as the Human Genome Project—but in the case that Palin was criticizing, the research was even more practical. The work was being done on olive tree fruit flies, a serious agricultural pest, and stood to make a major contribution to an important segment of the US economy. She didn’t know the particulars of this, and it seems she didn’t care, but instead went after the work because she didn’t understand how it could be valuable. You can read more about that episode here: https://www.science.org/content/article/french-fruit-fly-fracas
The reason I bring this up is that the same playbook is now being used by politicians and pundits from conservative backgrounds to try to bring down the NIH, NIAID, and Tony Fauci. They have latched on to a small NIAID grant that supported experiments in which 28 dogs were used to study a disease called leishmaniasis, which is spread by sand flies. Manipulative communications about this study have claimed that sand flies were allowed to feed on the dog’s faces, creating the misimpression that this was some kind of sadistic zombie apocalypse scenario.
In fact, sand flies are very small insects that bite the exposed tissue of mammals with whom they come into contact. This can include rodents, dogs, and also members of the US military stationed in countries like Iraq where sand flies are common. Leishmaniasis, which is caused by microbes spread by the flies, can take many forms, but one of the disease manifestations that is well known among US service members is colloquially called “Baghdad Boil,” referring to the boils that infected sand fly bites can produce. The disease can be disfiguring, and can also cause disabilities. It’s no joke, and it doesn’t just affect the US military. It has a huge effect on people in developing countries where the disease is endemic, and is considered a “neglected disease,” a term that encompasses serious infectious illnesses that do not receive enough research or attention from the international healthcare community.
As it turns out, domestic dogs are a huge reservoir for the parasite that causes leishmaniasis, and it is important to understand how the infection functions in dogs, in order to better protect the human communities that live adjacent to them. As a result of this, a model disease system has been developed in domestic dogs for the purposes of leishmaniasis research. You can read more about that and other model systems for leishmaniasis study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085833/
As an emerging infectious disease expert, I often take it for granted that everyone is aware our species is continually under assault from microbes that live in the animals that humans interact with, but I think most people just don’t realize how the animals around us are vectors for diseases that can range from inconvenient to globally disruptive. We don’t get anywhere by writing off a pathogen or reservoir as unworthy of study. Of course we have to have priorities, but each such entity is a threat, and is it really smart to turn our backs on a threat?
Particularly a threat that disfigures people?
Like the NIH and NIAID, I think the answer is “no.” I wouldn’t dedicate the entirety of my research budget to leishmaniasis, but I certainly would not want it to be overlooked, either. And I’m glad that the people who funded this grant agreed.
I will admit that I do not love the idea of using dogs in research. I do not love animal research in general. It is not pleasant to do, and I won’t sugar-coat the fact that despite serious efforts at harm reduction, animals are intentionally hurt in the process. There are safeguards and oversight mechanisms in place, but if we could live in a world where animal research wasn’t necessary to fight important disease, I’d love it. Unfortunately, current technology doesn’t allow us to live in that world.Maybe one day we will live there, and that will be great.
However, in the world we do live in, it’s important to understand leishmaniasis and how it works in dogs. This work might help prevent it in many thousands or even millions of dogs as well as human beings. The NIAID was doing what Congress created it to do in funding this work.
The criticism being leveled is another one that comes from a place of ignorance. It attempts to portray this work as pointless harm to a population of sympathetic animals, without any contextualization of the need for the research, nor the fact that it is within NIAID’s mission. The purpose of the criticism is to undermine respect for an institution that was created to save human lives, because that institution is currently politically inconvenient for a particular party.
This is callous and unscientific, and it’s the kind of thinking that got us into a world where we have SARS-CoV-2. Continual disregard for nature, an unwillingness to fund research into disease, and a disrespect for the earned expertise of our public health institutions created the conditions that led us to the current pandemic, and that will lead us right into the next pandemic, too. The most dangerous disease that we face is one of the mind, that tells us it is OK to live in ignorance of threats that will still exist even if we do not study them. All that happens if we study these threats is that we gain the ability to understand them and defend ourselves. We cannot let petty politics erode that vital function of scientific research.
What am I doing to cope with the pandemic? This:
Going to a wedding
I can’t imagine what it has been like to try to plan a wedding during this pandemic. I’ve been to a few, in various forms, and all have been difficult for the couple to arrange and required more thoughtfulness and compromise in arranging an affair that is already quite complex to set up in typical circumstances.
Several folks who I know have had to postpone their weddings, a decision that I don’t think is ever easy. The wedding I’m attending this weekend is like that, and I know the couple are very excited to finally have their big day.
For my part, I am incredibly grateful for vaccines that will allow me to be a part of this experience with my dear friends. Hopefully it will be all the better for their having had to wait.
Reader Mei-Ling Eckman asked the following on the last issue:
If a person or child already is confirmed to have had COVID and recovered, why is there no alternate protocol for them? Perhaps a single dose in "x" amount of time from recovery confers "y" level of protection equal to that of a two dose regimen. Maybe a chart of antigen titers and dosage regimens of the three vaccines?
I realize for simplicity sake a vaccine card says fully vaccinated or partially vaccinated.
But some would like the unneeded extra doses to go into arms that are willing in countries that have less vaccine readily available netting more fully protected people, but I know that isn't how it works because distribution logistics are complicated especially with the storage requirements and shelf life of mRNA vaccines etc.
It’s a good question. My answer:
Right now it is very hard to confirm that a person has an appropriate level of protection, and there is wide variation in the immune responses to infection. What you're saying--using infection as a stand-in for a single dose of vaccine--has been proposed by several individuals, but it just isn't as straightforward as that.
To make it possible, we would need an easily-measured correlate of protection that could be used to confirm that a person is protected. The threshold level of this correlate would probably be different per certain patient demographics, and it is not super straightforward to assess what that correlate should be. Neutralizing antibodies are one candidate that has been proposed, but it is actually not that easy to assess levels of neutralizing antibodies. You need to do something called a virus neutralization assay--it can be done with a stand-in for the virus, but can also be done with actual SARS-CoV-2 virions as well--and then the same exact assay has to be used as the benchmark diagnostic in every testing lab everywhere. That's a relatively tall order.
The antibody tests that are on offer from various testing labs just look at reactive antibodies, not neutralizing ones. While neutralizing antibodies are a subset of the overall SARS-CoV-2 reactive antibodies, it is not at this time clear what the relationship between overall anti-SARS-CoV-2 spike antibodies and neutralizing anti-spike antibodies may be. There has been some work on this, but it is not yet at a place where we can use it clinically for reliable diagnostics.
Then of course there is a question as to whether the numbers might be different in children and adults, because of the difference in disease severity seen by age. We would need to make sure that the correct correlate threshold is being used.
There are a lot of unanswered questions to be addressed in the push towards being able to test someone for immunity, but the ability to do that is, in my opinion, one of the biggest unmet needs in COVID-19 control today.
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. And don’t forget to share the newsletter if you liked it.
Current technology does allow us to stop animal testing on cosmetics and personal hygiene products, and I fully support moving away from the use of animals in such contexts. However, when lives are possibly at stake, and there is no alternative, I do not think it is morally appropriate to let humans die for the sake of laboratory animals that would never have been born if not for their use in research.
Merck's free licensing of molnupiravir (to the Medicines Patent Pool, not WHO, by the way) will end when the pandemic is declared no longer an emergency by WHO. Considering how short patent terms are, this will probably be right at the end of its patent life anyway, of course. (I'm assuming WHO will be slow to un-declare an emergency, given that they're part of the notoriously dilatory United Nations.)
I think the weird "They're harming beagles!" freakout by some politicians is especially misguided because, as you mention, Leishmaniasis research can (and presumably will) also be used to protect dogs.
I just discovered two YouTube videos by medical researcher Susan Oliver (https://www.unsw.edu.au/staff/susan-oliver) explaining why ivermectin has not been shown to have value in treating COVID-19. Part 1 is here: https://youtu.be/-zWK_-4mfXs