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Monday, March 16, 2020

Plasma therapy for coronavirus

Here is an interview with an infectious disease and vaccine expert named Peter Hotez (MD, PhD). However I just want to excerpt a segment from the interview. The excerpt starts at approximately 16 minutes.

[Peter Hotez:] I introduced this new concept this morning, both on CNN and on Fox News - and I did it after calling my friend and colleague Arturo Casadevall, who's a professor at Johns Hopkins, who has been pushing this idea for a few weeks - that there is a low-cost intervention that we could apply right now. And that is: identify patients who have been infected, recovered, and look at their convalesced serum. In other words, looking people who have developed antibodies and antibody response to varying degrees, collecting that serum, isolating that antibody, and then using that as the treatment.

Because that's all we're going to have right now. I already think the window has passed when we're going to start having significant numbers of people sick from this virus in hospitals and in intensive care units. But this is the one thing that we can offer them, given the fact that we're not likely to have any effective antivirals drugs for a while.

And it could be very effective based on what we've learned historically from things like the 1918 flu pandemic, the Spanish flu, or even from experiences that we've heard about from SARS and MERS or even this virus in Wuhan. Both as a treatment, which would require large amounts of antibody, but also as prophylaxis, so you can give a small amount and keep healthcare workers and first responders on the job because it's preventing them from eventually getting sick.

[Peter Attia:] Peter, when it comes to convalescent serum, I want to make sure I understand something. From a technical standpoint, this is easy. Obviously from a theoretical standpoint, it makes sense. This is, as you point out, not a new trick. However, when we start to think about bottlenecks in the supply chain, it does require apheresis, correct?

[Peter Hotez:] Yeah, it looks that way, and so we really need the help of blood banks and any academic health centers. I don't know if we do this only in academic health centers or whether every community hospital would have this capability. And we would need some guidance from the Food & Drug Administration (FDA), from CBER, the Center for Biologics Evaluation and Research. So this is a kind of 30,000 foot aerial view of the problem. Speaking to Arturo, he thinks putting together a federal task force to really look into this and to help with standardizing it and figuring out what we can do.

But if we wind up having a situation similar to Italy in the United States, or even part of the United States, having this at our disposal could be really important because otherwise we've got nothing. Otherwise we go back to the 14th century in terms of using quarantine methods and that kind of thing. And we've seen what happens when we have to do that. It's not a good look for our country.

[Peter Attia:] Peter, do we have a sense of how many individuals could be helped by the serum of one convalesced patient? How scalable is it?

[Peter Hotez:] The kinds of numbers people are throwing out are 300-600 mLs for someone who is potentially seriously ill. So that looks like a 1:1 donor per patient. [Ian Lipkin noted a 1:3 ratio with 1 donor treating 3 patients.]

But for the prophylaxis, if we're talking 5 mLs, then a single donor could potentially prophylax dozens or maybe even a hundred individuals.

And who knows how off those numbers really are. But given the fact that it's relatively low-technology, doesn't need to bring in a lot of specialized equipment, I don't think, I think it's something we need to look into.

And Arturo gave me the permission to the sound the alarm on CNN and Fox News. We'll see how it resonates in the coming days and weeks and see if it catches fire.

1. Let me start with a broad overview. I'm simplifying, but there are several different ways a person can become immune to a disease.

a. First, someone could simply contract a disease, get sick from it, and, if they survive, then they'll be immune to the disease in the future. For example, this happens with a lot of kids who get chickenpox.

b. Another way to become immune to a disease is by getting a similar enough but weaker disease, getting sick from it, and recovering. This will confer immunity on the person too. A classic example comes from the father of immunization himself, the English physician and pious Christian Edward Jenner. Smallpox ravaged England in Jenner's day. But Jenner noticed milk maids didn't seem to get as sick from smallpox as others did. He realized the reason was because they had been exposed to cowpox. Cowpox was a far less serious disease than smallpox, but contracting cowpox meant smallpox would have a less severe effect on them.

c. A third way to become immune to a disease is by getting vaccinated to the disease. I think most people are familiar with vaccines today. A physician or nurse injects a crippled (attenuated) or killed (inactivated) form of a virus, the virus infects them, the infection activates our immune system, our immune system develops antibodies against this virus, and the person is immune from the disease caused by the virus.

d. A person can become immune to a disease if someone transfers antibodies from another person who has antibodies against a particular disease and into them. This is what Hotez is advocating. It's called passive immunity. He's advocating conferring passive immunity to people. For example, passive immunity naturally happens in every pregnant woman. Babies are conferred antibodies from their mother in the womb as well as shortly after birth with the mother's early breast milk (colostrum).

2. In short, Hotez is speaking about taking antibodies from people who have survived COVID-19 and putting these antibodies into other people in order to help them. Either help them recover from COVID-19 or help prevent them from developing COVID-19 (prophylaxis).

3. Of course, there are medical issues that would need to be worked out (e.g. allergic reaction, TRALI). However, what Hotez is proposing is certainly a very viable therapy. Indeed, it's been known and used in medicine for over 100 years. It's not technically difficult to do, but it would be logistically difficult to do (as Hotez points out in his interview). But it could hold us over until antivirals and vaccines are developed. A coronavirus vaccine isn't expected for at least another year.

4. I'll also note another infectious disease expert, Ian Lipkin, mentioned the same therapy several days ago.

5. Here is a paper on the same therapy published in the prestigious medical journal The Lancet.

10 comments:

  1. This comment has been removed by a blog administrator.

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    1. Your comment is off-topic. This post is about the coronavirus and plasma therapy. It's not about vaccines. Please stop pushing your anti-vaccination agenda. Or at least do it in my other post that is about vaccines.

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  2. "A coronavirus vaccine isn't expected for at least another year."

    Any idea what Charlie Kirk means (retweeted by Eric Metaxas) that, "The first participant in the clinical trial [for a new vaccine] will receive his test on Monday [i.e., today].

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    1. Thanks, Pat! Good question.

      In general clinical trials work in 3 distinct phases. Phase 1 is usually with a small group of volunteers (maybe 30-50 people) with the goal of testing for safety (e.g. no bad side effects). Phase 2 expands this group to a few hundred people with the goal of demonstrating safety and efficacy. Phase 3 is much larger (often thousands) group of people with the goal of demonstrating safety and efficacy in natural disease conditions. Normally this entire process can take between 2-3 years but I believe it's been accelerated for the coronavirus vaccine. Even still it could be at least a year away.

      I haven't looked into the specific details, but I believe the first participant in the clinical trial simply means the first person to start Phase 1 trials. He or she should be one person in a group of maybe 30-50 other people. If I'm not mistaken, it's the joint NIH-Moderna trial. However there are many other companies doing trials too. Of course the NIH is huge and represents the federal government, hence all the press.

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    2. Actually, sorry, I should have said there are many other companies attempting to develop a coronavirus (SARS-CoV-2/COVID-19) vaccine. I don't know how many have progressed to clinical trials. They might still be in pre-clinical (e.g. animal testing).

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    3. I talked a little bit about what Moderna is attempting to do back in Feb, but it might be outdated information at this point:

      https://triablogue.blogspot.com/2020/02/a-coronavirus-vaccine-on-horizon.html

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  3. Replies
    1. Just saw this on article on the first patient injected with a coronavirus vaccine:

      https://www.forbes.com/sites/victoriaforster/2020/03/17/first-person-injected-with-trial-coronavirus-vaccine-in-seattle/

      It is indeed from Moderna and the NIH. And it's indeed in Phase 1 trials. She's a patient in Seattle.

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  4. Just curious... how do they determine how long each phase of the trial should last?

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    1. There's no absolute or mandatory length to each phase. It's really when the goals of each phase have been sufficiently met. Phase 1 could be several months, Phase 2 could be a year, Phase 3 could be a couple of years (or even longer). (And we could subdivide, e.g., Phase IIa, IIb.) It really depends.

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