NATURE PODCAST

Coronapod: Old treatments and new hopes

Could blood plasma from coronavirus survivors be an effective short-term treatment for patients?

Benjamin Thompson, Noah Baker, and Amy Maxmen discuss efforts to develop treatments for COVID-19.

In this episode:

02:00 A push for plasma

In New York, hospitals are preparing to infuse patients with the antibody-rich blood plasma of people who have recovered from COVID-19. This approach has been used during disease outbreaks for over a century and we discuss how it works, and how effective is might be.

We also talk about how drug trials for potential treatments are progressing, how scientists are pulling together, and what COVID-19 outbreaks on cruise ships are telling epidemiologists.

News article: How blood from coronavirus survivors might save lives; News article: What the cruise-ship outbreaks reveal about COVID-19

18:44 Switching focus

In the wake of the outbreak, academics are coming together to meet the challenge of the pandemic. We speak to an immunologist and a bioengineer who have changed their research focus and are putting their expertise into action.

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Transcript

Benjamin Thompson, Noah Baker, and Amy Maxmen discuss efforts to develop treatments for COVID-19.

Benjamin Thompson

Welcome to Coronapod.

Noah Baker

In this show, we’re going to bring you Nature’s take on the latest COVID-19 developments.

Benjamin Thompson

And we’ll be speaking to experts around the world about research during the pandemic.

Amy Maxmen

I really don’t know how this plays out. We also don’t know a ton about this virus. There’s so many open questions. I just have a really hard time making predictions because I don’t know how the outbreak is going to change.

Benjamin Thompson

Hi, Benjamin Thompson here with episode two of Coronapod. I’m in my South London basement, and once again I’m joined from dozens of miles away by Noah Baker, Nature’s chief multimedia editor. Noah, hi.

Noah Baker

Hi, yeah, I’m also sitting back in my little booth talking to California, as you do in a pandemic.

Benjamin Thompson

Amy, you’re thousands of miles away, and you’re Amy Maxmen, of course, senior reporter here at Nature. How are you doing?

Amy Maxmen

I’m good. How are you?

Benjamin Thompson

We’re doing okay here, I think. I mean last week we all spoke about being in lockdown. How are you both coping with it?

Noah Baker

Lockdown has intensified in the UK, so the government has now officially said that we by law aren’t allowed to go outside and there shall be fines. Our Prime Minister, Boris Johnson, and our health minister, Matt Hancock, have both now tested positive for the coronavirus, so they’re self-isolating. Everything has become even more real, if possible.

Amy Maxmen

Yeah, over here it seems fine. I’m just growing out my bangs and my toenails. But I just talked to one of my sources, and he pointed out something very wise, which is the disaster right now in the hotspots is inside of hospitals. So, it looks really good here, but if you see any of the reports coming out of New York City, for example, it’s just terrifying.

Noah Baker

It is amazing, the difference, actually. So, I’m sitting here in a rural area and it’s sunny outside but I have friends that are contacting me that are currently in ICUs, and it’s this really strange comparison between relatively sort of the world is standing still and this warzone within the walls of hospitals.

Benjamin Thompson

Well, maybe we should head straight away to hospitals in New York then because I know that’s something that you’ve been looking at this week, Amy, and some scientists who are searching for, I mean I don’t know if treatment is the right word or what it is, but people who are searching for something to try and fight the virus.

Amy Maxmen

Yeah, so right now in New York, it’s really under siege. So, there’s been more than 30,000 cases and 325 deaths, and hospitalisations seem to be doubling every four or five days. Governor Cuomo is yelling about how they don’t have enough ventilators to kind of serve the growing population, or not right now but in the near future, so it’s really suddenly gone form a thing that oh, this seems to be spreading in the community to wow, our hospitals are being overwhelmed. There’s reports of nurses there who don’t have protective gear, so it’s already at kind of disaster point and as kind of a sign of how dramatic it is, now there’s kind of a push to use the blood from people who have recovered from coronavirus to help patients. It’s something that doctors have used for the past century in outbreaks, but it’s kind of like an old, brute force sort of thing, where you hope that the person who survived has made enough antibodies that you can then take their blood after they’ve recovered from the virus, kill the viruses within that blood and then put that into somebody that has the disease, hoping that the antibodies from the other person help them fight off the virus.

Benjamin Thompson

So, is this just a case of taking someone’s blood, centrifuging it and then injecting that physically into somebody else, or is there more to it than that?

Amy Maxmen

No, you’ve got it. I mean you’re going to screen that serum and all of that. Besides that, yeah, that’s basically it. So, the hope is that they can kind of start putting survivor blood into patients as early as next week. The FDA just classified convalescent plasma – that’s a more precise term for survivor blood – as an investigational drug, which means that doctors can decide to use it compassionately even though it’s not approved like a drug would be. And it also means that now, the FDA can start evaluating protocols from researchers who want to run trials on convalescent plasma to see does this actually work.

Noah Baker

I have to say, Amy, that when I first heard this story as well, then you starting telling me about it, I was also really shocked. It feels like century-old technology. It feels like century-old medicine, and you don’t expect it to be happening in New York City.

Amy Maxmen

No, I was surprised too, and I have to say, I keep being reminded of when I was reporting in Sierra Leone during the Ebola outbreak. A lot of the things I saw there are happening now, and this is one of them. For example, when I was in Sierra Leone, there was a big push by some of the clinician scientists there to try out convalescent plasma as they’re doing right now, and their push was like hey, I know you’ve got Ebola drugs in development but we need to do something right now, and what do we have right now? Right now, we have survivors. And another similarity is in both cases you have just really the goodwill of people who have recovered from – it was Ebola before and it’s coronavirus now – people who’ve recovered who say I want to help, I want to give my blood. So, it’s a product that people have right away.

Benjamin Thompson

And New York isn’t the only place considering this approach, right? China has also been running trials.

Amy Maxmen

China ran a number of trials. So, China was on this pretty quickly as well, so they were running trials on convalescent plasma. Those trials aren’t published yet so I don’t know how many people actually ended up being enrolled, but early data that’s come out in preprints and that I heard about through emails with some of the investigators involved are that in small numbers of people, I’d say 13 patients who are infused, nothing bad happened. So, there were no adverse reactions, which is very important.

Noah Baker

I wonder, maybe kind of a naïve question, do we already sort of have a bit of a safety trial in that these are essentially blood transfusions which are done every day, or is there really potentially a risk that blood transfusions with people with these antibodies could be dangerous?

Amy Maxmen

So, yeah, it does seem relatively low risk because, right, exactly, this is a product that’s –blood – used all the time, and we do know that although the risk is not zero, it seems like especially in places like the US, we have the ability to get blood transfusions safely. There is another thing people are worried about. It’s called antibody enhancement, and I don’t – to be honest – I don’t fully understand it but the idea is that you might cause a massive sort of inflammatory response that could happen, and that’s been a fear. So, that’s why the data coming out of China from the preliminary study, that kind of suggests okay, hopefully we don’t need to worry about that a lot.

Benjamin Thompson

Do we know maybe how long protection might last for someone who does receive this serum, and when’s the best time to give it to them?

Amy Maxmen

So, that’s an open question is how long it lasts. One researcher who is leading this effort who I spoke with, she said it might not last more than a couple of weeks. In fact, she doesn’t think it will. With a vaccine, you get somebody to generate their own immune response that lasts longer. This is not that, so it might only be for a couple of weeks, but that would be enough. All of the researchers I spoke with were very clear that they really hope that this is used either to prevent COVID-19 in people who at high risk, namely health workers, or soon after an infection, within five days of symptoms, before people start going into respiratory failure. So, in the case of a person who’s within five days of showing symptoms, if you’re able to prevent them from needing to go on a ventilator to breathe and to get into the ICU, the intensive care unit, that’s huge. So, this is kind of a stopgap measure. It’s maybe not something that’s going to increase your survivorship a ton, but what it will do is if you’ve got patients who are severe enough that they’re going in to the hospital but don’t yet need to be on a ventilator, it means if you can prevent them from getting on to a ventilator, then those beds are free for people who need them, and the more people you can keep out of the ICU, the better on hospitals that is.

Noah Baker

I’m also interested because this technique seems like something that if we look forward at the potential challenges that are coming up, it’s something that if it were to work could be really, really useful to countries that have fewer resources than the States.

Amy Maxmen

I mean I think that’s a great point, especially because we don’t know what resources are going to look like. There’s an antiviral drug – remdesivir – that’s being tested. People are talking about chloroquine, this malaria drug. What if there’s stock outs, which I don’t see why that’s not impossible. What if countries can’t afford those drugs? Blood is relatively cheap. Of course, you need to have the ability to screen blood and do transfusions, but yeah, in some ways, it seems much more practical. And I think, to be clear, I think the idea of isolating antibodies and formulating them into drugs is better. I think that’s a great idea. It’s just that it’s going to take some time, and once those are made, those also might be very expensive and we could have patent issues with those, so blood is a sort of a practical measure.

Benjamin Thompson

Well, Amy, you mentioned several other drugs there as well – chloroquine is the one that’s getting a lot of attention at the moment. What’s the state of play for people looking for other treatments that can be used?

Amy Maxmen

The fact is, on chloroquine, we don’t have much data right now. I think President Trump overstated what we know about it, and there’s a couple of drawbacks. One is it very likely can have side effects, so it’s not something that people should take frivolously. I think there’s been a couple of deaths from people who did just sort of take it on their own. The other thing to keep in mind is people still use that for malaria and for other diseases, so it’s not something we just want to stock out of right away. Originally, so, China’s tested it and they tested it based on pre-clinical work in animals, suggesting it could have some benefit. I haven’t seen all of the data out of China on chloroquine, but it’s very much still an open question at this point. The WHO launched a four-arm clinical trial that’s going to be run in several countries that’s comparing the antiviral remdesivir to this HIV drug combination to the HIV drug combination plus interferon, which also has side effects, and then comparing that one to chloroquine. So, it’s a kind of head-to-head trial to look at the effects of all of these, which will be nice.

Noah Baker

So, we’re talking about what we can do at the moment with developing vaccines, developing drugs. These things are, I guess to some extent, they’re exciting, they’re the endgame, they’re the future, they’re the cure – there’s always this tendency to look for the cure – but at the same time, there’s these other measures. There’s these measures like social distancing, these measures like contact tracing, which may be a less sexy, maybe less sort of exciting. They’re not the endgame, but they’re still important.

Amy Maxmen

Oh, it’s so important, and I think maybe that’s one reason why we’re so behind right now in the US and in Europe, is there’s been a big focus on vaccines and drugs and yes, those are incredibly important – I mean vaccines might be how, in the end, we get out of this thing –but that’s not going to help us in the next year at least. So, my big fear in the US is, if you remember in China, the government was also very slow to kind of acknowledge that they had an outbreak, but once it was clear that it was big in Wuhan, not only did they lockdown Wuhan but they also very aggressively began testing and doing contact tracing across the country. What really worries me about the US is we do not have a cohesive response right now. So, we can see that New York is a disaster. We saw that Seattle was being hit hard a few weeks ago, and yet at the same times, we have certain states that are still discussing whether or not they want to do social distancing. I know just a few days ago, I’m not sure about right now, Florida still had all of their restaurants open, people were still out and about, there was big spring break parties on the beach. That’s really worrisome.

Noah Baker

There are even some countries in Europe right now that are taking a different tack. The current proposal in Sweden is that they still haven’t closed things.

Amy Maxmen

Yeah, it makes me nervous.

Noah Baker

And, of course, as this develops, there are these natural experiments that keep popping up which are teaching us really invaluable things. So, one thing that people have been talking about this week is the people that have been stuck on cruise ships have actually provided epidemiologists with a really vital tool to sort of study how this virus moves between people, and those results are now coming back.

Amy Maxmen

Yeah, the cruises are interesting because a big problem is that we haven’t been able to get a handle on the denominators in this outbreak, like by not knowing how many people are infected either asymptomatically or with mild symptoms, it’s really hard to answer some basic questions. So, the cruise, particularly the Diamond Princess cruise off of Japan that had 3,700 passengers and I think I heard more than 3,000 of them were tested, so that just basically gives us some place to start. And so, the data that’s come out from that is that there was a case fatality rate of 1.1%. That means of all the people who had symptoms who were cases, 1.1% of them passed away. They also had an infection fatality rate and that’s something I really haven’t heard a lot about. That’s how many people are infected asymptomatic or symptomatic and that’s 0.5% of those ended up dying, so that’s a 0.5% infection fatality rate. Those are useful numbers to have because so far, we’ve really only been able to guestimate at the case fatality rate, and that varies depending on the country and over time because various hospital interventions will keep people from dying and also the number of cases that are detected varies, so it’s nice to have that 1% number.

Noah Baker

Absolutely, it’s so helpful to have this sort of cruise experiment, I suppose, as baseline data because otherwise it’s really hard to compare different approaches and different places and different hospitals when all the numbers have so many different variables with them, and I think that’s a story we could continue talking about as time goes on.

Benjamin Thompson

Although government might be taking different tacks, as you say, it seems that scientists are pulling together.

Amy Maxmen

Yeah, I think that’s kind of a really, if there’s something that’s cool about this outbreak, that’s it to me. The way that scientists are sort of, traditionally they’re competitive with one another. I’m just seeing scientists from every field suddenly not be competitive and just really drop what they’re doing in other ways to help out with the response however they can, and this convalescent plasma business is an example of that. There’s a researcher at John Hopkins who, about a month ago, realised that convalescent plasma might be really important here, and he kind of had a tactic where he first decided he wanted to get the idea into newspapers so that everybody would start talking about it, including politicians, so he wrote an op-ed for the Wall Street Journal. Then he got a bunch of people doing all sorts of things – statisticians, immunologists, epidemiologists, clinicians. It ended up being about 100 of them, and what I heard was that they started working on this in their separate lanes. So, say, the statistician started working out, okay, how are we going to share data, what data are we going to collect, and the people who knew about blood transfusions talked about how they were going to actually do that logistical part of it. The virologists started talking about okay, what kind of assays can we use to look at antibodies. They talked to people they knew who knew about regulations because we need to get this through the FDA, we need to get institutional review boards to approve the ethics of this study. And they have a site now where they’re sharing their protocols online, so they want to have as many institutions that are interested that are affiliated with hospitals start working on this, and I think the list already includes Albert Einstein College of Medicine in New York City, there’s Mount Sinai, they’re working with John Hopkins, Washington University, the Mayo Clinic, and I’ve heard that other universities are also signing on to it too. So, that’s just another effort. It’s similar to what we talked about last week where the scientists who were at that small NIH meeting realised they had to do a grassroots effort in contact tracing. I even talked to one researcher who was telling me that she’s been hooking up with kind of more early career scientists who are no longer working in their labs who have offered to help them write grants because the people who need to be doing research right now on coronavirus don’t have time to be writing grants. So, there’s people who work in different fields who just know about a field who can help them write grant proposals.

Noah Baker

Nature actually published an editorial in its pages this week which I think we just titled, ‘We’re with you’, and the intention was just to say that Nature is facing a lot of the same problems that other people are facing, and we’re struggling to create an issue and we’re trying to commit to do things to try to help as much as we can.

Amy Maxmen

It makes me proud.

Noah Baker

It makes me proud too, I have to say.

Benjamin Thompson

Yeah, I’ll add my voice to that as well. I think it’s amazing work from everyone who is doing the research right now. Amy, what’s catching your eye then for the next seven days? Obviously, this is a massively sort of moving and developing story, but what are you interested to hear in the forthcoming days?

Amy Maxmen

Well, I’m looking at a few things. I think usually I write about, I mean I’ve been covering outbreaks for a really long time now. I’m used to covering low-income countries and lower-middle-income countries, and suddenly I find myself in the middle of an outbreak that looks very much like what I’ve seen in other places, but I’m here. So, I’ve been really putting my head around what’s happening in the US. However, I think in the coming weeks I’m going to be taking a more global view and seeing what are other countries doing. I think what we’ll start seeing in some countries that we might not have expected having a really sleek response and of course other countries are going to be hit just terribly. Think about places that don’t have any ventilators.

Benjamin Thompson

Yeah, agreed, and there’s so many more questions, as I said last week, to ask, and I hope you’ll both join me again next week to keep going through them. So, Amy and Noah, thank you so much.

Amy Maxmen

Thank you so much, Benjamin and Noah.

Noah Baker

Yeah, thanks everyone and stay safe at home.

Benjamin Thompson

As Amy mentioned, researchers are really pulling together in these difficult times and in many cases, they’re shifting focus or changing lanes completely to help in the fight against COVID-19. Reporter Nick Howe spoke to a couple of researchers who are putting their expertise into action.

Nick Howe

Across the world, labs are shutting down and scientists are finding themselves in lockdown.

Julio Valdivia

Right now, we are in isolation, quarantine.

Nick Gherardin

There’s far fewer people around and at certain times of the day it definitely feels like a bit of a ghost town. It’s a very strange, strange situation.

Nick Howe

But instead of completely closing up shop, many scientists are mobilising to tackle the coronavirus. I’ve reached out to some of them, and here are a couple of their stories. First up, I spoke to Nick Gherardin, a researcher at the University of Melbourne in Australia. When I spoke to him, Australia hadn’t implemented the sort of lockdowns we’ve seen in many parts of Europe and China, but it had closed all but essential businesses. Labs were shutting down too. Nick has still been going to work, but that’s because his lab had been moving towards working on coronavirus.

Nick Gherardin

It sort of started off very slow. As we were sort of watching the situation evolve coming out of China, I guess, there was growing interest and also growing concern about the situation, so we started dabbling a little bit and sort of thinking is there any possible way we could get involved. That very, very rapidly, as the sort of pandemic spread and it was all of a sudden on our shores, it was a very, very rapid transition to okay, now we’re only working on COVID-19.

Nick Howe

When labs started shutting down, Nick said there wasn’t really much of a question of whether he would continue to go in or not.

Nick Gherardin

I’m personally really excited, actually, to be able to come in and get involved in this work.

Nick Howe

The same was true of many of his colleagues. He told me that everyone was trying to see how they could help with the situation. Nick works on immunology, looking at how white blood cells can recognise infection, which made the switch to coronavirus quite straightforward.

Nick Gherardin

We have excellent experience with generating proteins in the lab, so we were able to clone and generate recombinant proteins and then use these proteins to assess immune responses from other blood samples or patient sera or these sorts of things.

Nick Howe

Nick’s work on the virus is still in the very early stages, but he says it could potentially be leveraged towards diagnostics or even treatment applications. As everyone pulls together, Nick says the next few weeks and months are going to be very busy for him and his colleagues, but he’s trying to stay optimistic.

Nick Gherardin

I try to keep a positive outlook. I think we’re in for a pretty interesting few weeks and months ahead. I think there’s going to be a lot of heartache. There’s going to be a lot of really sad stories to come out of this, but I think ultimately, it will pass.

Nick Howe

I also spoke to Julio Valdivia, a scientist at the Universidad de Ingenieria y Tecnologia in Lima, Peru. At the moment in Peru, there around 600 cases of the virus – relatively few compared to many countries. But as Julio told me, the government there had swiftly locked things down. You can only leave your home for essential purposes or if you have special permission. Julio is a bioengineer, so he has such special permission, and he’s been using it to help develop a new kind of ventilator.

Julio Valdivia

Because in the entire country we have just 400, so it’s not enough to help people if the situation goes to a worse scenario.

Nick Howe

At tens of thousands of dollars per unit, Peru cannot afford the numbers of ventilators that they may need, so Julio has been helping to create the kind that would be cheaper and more readily available. He and a team of engineers have helped develop an early prototype. It’s got a way to go, but costing only US$500, he thinks things are looking promising.

Julio Valdivia

Because we are using different parts it’s just like a Frankenstein prototype, but our prototype is, I think, working very well.

Nick Howe

While it may be a bit of a Frankenstein’s monster, Julio’s prototype ventilator is smaller than conventional ones, and would be easier to mass produce. He hopes it will be able to help in resource-poor places that may be more at risk. But it wasn’t straightforward for Julio to start working on making ventilators. Previously, he had worked on microfluidics – technologies to manipulate fluids – which are quite different from a ventilator. But he did have some other skills though. He’s got medical experience and has worked for NASA, so he knows a thing or two about getting people the right amount of air.

Julio Valdivia

I’m trying to bring this knowledge together, these various areas together, with other researchers, engineers as well, trying to think about all solutions but more local solutions.

Nick Howe

There are still some kinks to be worked out in Julio’s ventilator. But there are a number of other teams around the world working on this problem, and Julio says they are all cooperating.

Julio Valdivia

We are comparing our prototypes with the MIT – right now, MIT have launched a prototype – and we are comparing with Columbian people that have another prototype, so the interesting thing now is we are having more communication. At the same time we’re supporting initiatives to build components for simple tools that help doctors, such as masks or protectors using 3D technologies as well. It’s a different area. More people are trying to help and this is very nice.

Nick Howe

We are clearly living in extraordinary times, and researchers are coming together to meet the challenge of the pandemic. If there is a positive to come out of the outbreak so far, it’s the solidarity of the science community. Here’s Nick from Australia again.

Nick Gherardin

The work that I’m doing at the moment, we’re doing it highly collaboratively, and sort of almost in an unprecedented way. We’re working with other institutions and doing things that would otherwise normally require lawyers getting involved and that sort of thing, and we’re just pushing ahead. And so, there is also a really good sense of comradery in the community at the moment, not only within our institute, but across institutes and around the world I think.

Benjamin Thompson

So, that’s it for another edition of Coronapod. You can find all the latest news on the outbreak over at nature.com/news. We’re back again next week with another edition of the show. If you’d like to reach out to us with stories of how the outbreak has affected your lab work or if you’d like to send us a picture of your home working setup then you can do so on Twitter – we’re @NaturePodcast. And speaking of Nature Podcast, there’s a corona-free version of the regular show coming out on Wednesday as usual. I’ve been Benjamin Thompson. Thanks for listening.