Are New COVID-19 Treatments More Important Than a Vaccine?

John Whyte, MD, MPH; Davey Smith, MD


October 06, 2020

Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

  • The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) initiative is a public-private partnership through the National Institutes of Health to support a coordinated research strategy to develop promising COVID-19 treatments and vaccines.

  • Developing COVID-19 drugs could help people live longer and slow the spread of the virus. They could also be used as prophylactic treatment.

  • People who have severe COVID-19 are treated in the hospital with such drugs as remdesivir and dexamethasone. However, there is not a single treatment for people who show early signs or mild symptoms of COVID-19.

  • Making monoclonal antibodies that specifically target SARS-CoV-2 is expensive and complicated. However, about 20 companies are working on creating these drugs, and we could expect an effective treatment by the end of 2020.

  • Developing COVID-19 drugs to treat people with mild cases is critical and may be more important than developing a vaccine, which will probably not protect everyone nor last long-term in an individual.

This transcript has been edited for clarity.

John Whyte, MD, MPH: Welcome, everyone. You're watching Coronavirus in Context. I'm Dr Whyte, chief medical officer at WebMD.

You can't turn on the news and not hear about a potential COVID vaccine. Should we really be talking more about potential treatments? Is that one of the most effective strategies to return to some sense of normal?

To help provide answers and insights into the role of therapeutics, I've asked Dr Davey Smith, the head of the Division of Infectious Disease and Global Health at UC San Diego in La Jolla, California. Dr Smith, thanks for joining me.

Davey Smith, MD: Thanks for having me, John.

Whyte: I want to start off talking about the ACTIV trial. Doctors are always good for acronyms, and I want to get it right. ACTIV stands for "Accelerating COVID-19 Therapeutic Interventions and Vaccines."

Smith: That is correct.

Whyte: Is it a public-private partnership with NIH?

Smith: That's a good question. So, there's a program at the US government called Operation Warp Speed. They developed this public-private partnership that they termed ACTIV to develop these coronavirus vaccines and treatments, basically as a way to efficiently and very quickly get some good vaccines and therapies out to the public.

Whyte: You're a big proponent of therapeutics, that we need to get treatments more accelerated, as well as any potential vaccine. Is that right?

Smith: That is correct. I'm very much a fan. If we could get a vaccine, that would be absolutely great, but we also need therapies. From our HIV experience, we know that therapies can really help people live longer, but they can also be used to control an epidemic. They both decrease the chance of somebody getting sick and decrease the chance of somebody spreading it. Those treatments could also be used as prophylaxis. They could really be very good tools in our toolbox to stop the pandemic.

Whyte: Do you think HIV/AIDS is a good comparison? In many ways, that's multidrug therapy as well. There's been some preliminary data to suggest that one-drug therapy is not going to be sufficient for COVID.

Smith: I don't really know. Those trials still need to be done. In the hospital setting, it is probably going to take more than one drug to treat COVID. In the outpatient setting, one drug might be enough.

Whyte: Tell us where we are on treatments. People are talking about remdesivir, dexamethasone, and monoclonal antibodies. Where exactly are we?

Smith: Right now, when somebody gets severely sick in the hospital, we have some therapies that seem to have a good signal for working, such as remdesivir or dexamethasone. There's also this new drug called baricitinib that's coming out.

We do not have a single treatment for outpatients before they get sick. They have early COVID, and some will progress to needing the hospital, but we just don't have a treatment for those people yet. That's one of the reasons that ACTIV-2 is testing those drugs.

Whyte: What are some of the drugs they are testing? Are they mostly drugs that are already approved and indicated for some other disease, or are you also thinking about new molecules?

Smith: Right now, we are looking at drugs that were made specifically to target SARS-CoV-2. The first ones that are going to be used are called "monoclonal antibodies." They are humanized antibodies that are specifically targeted to SARS-CoV-2 and are not repurposed drugs.

Whyte: Those drugs are hard to make, are they not? There are challenges in manufacturing. We have to sometimes worry about potential side effects, given the immune response. Can you give us a quick primer on the role of monoclonal antibodies?

Smith: Monoclonal antibodies are made from people who got the virus, and some of those people made really potent antibodies. We were able to select out and grow those antibodies and turn them into drugs. That process is complicated and can be very expensive to make. About 20 companies or groups out there have made these monoclonal antibodies specifically targeting SARS-CoV-2.

We've progressed a long way into figuring out how to safely produce those monoclonal antibodies now. I'm very optimistic that one or more of those will be ready to use soon for treating COVID-19.

Whyte: I'm going to put you on the spot a little. What does "soon" mean? Six months, a year, or 3 months? What's your best bet?

Smith: December. My best bet is that by the end of the year, we will have a pretty good new monoclonal antibody that will keep people out of the hospital. I'm optimistic, and I do believe that.

Whyte: Can we drive manufacturing for monoclonal antibodies to the level that we need?

Smith: That's a good question. We really need to figure out how much capacity each of these companies has to drive manufacturing. Operation Warp Speed has stepped in to say, "OK, if we find a good target, they are going to help drive manufacturing as well, especially for some of these smaller companies that might not have the resources to be able to do so."

Whyte: I'm looking at some of the information on Operation Warp Speed. It's interesting that you point out how Operation Warp Speed is also about therapeutics, but all the news seems to be around just vaccine development. Is that a disservice to innovation?

Smith: I don't know that it's a disservice, but I do know that the oxygen in the room is all being taken up by coronavirus vaccines. I get it, because we talk about vaccines so much in terms of everybody needs to get their flu vaccines and there's the antivaxxers with measles, and so on. We think that having a good vaccine will get us out of the pandemic. I am less optimistic on that point.

I think we also need treatments. The reason that I say that is the US Food and Drug Administration (FDA) has said that they will approve a coronavirus vaccine that works 50% of the time. If I get a coronavirus vaccine (which I will if it works 50% of the time) and then get exposed in the hospital, I still have a 50% chance of getting sick. I really need to have a therapy that's going to keep me from getting sicker and perhaps dying, even if we do have a vaccine that works 50% of the time.

Whyte: That might be 50% effective with two immunizations as well, correct?

Smith: That's right; it might be two immunizations. We also don't know how long that vaccine might last. In regular circulating coronavirus infections, we know that immunity wanes pretty quickly. We don't know what the duration is of these vaccines that will actually work. If I had a treatment, I would be a lot more optimistic of opening up businesses and so on. When somebody gets sick, I have something that I can do for them.

I'm an infectious disease doctor, and I see lots of people with coronavirus infections that get pretty sick. I want to be able to help them. But at the moment, I really have nothing to offer them before they get into the hospital.

Whyte: If people aren't willing to take the vaccine (because of concerns that it was rushed or about its safety), then we concomitantly have to be developing treatments, correct?

Smith: That is correct. We talk a lot about herd immunity. But if you have a vaccine that only works half the time, and only half the people take it, you're never going to have enough immunity within a population to get rid of that epidemic spread with this virus. We still need a treatment, and that's what ACTIV-2 is doing. We're really hoping that we can develop a treatment that can keep people out of the hospital.

Whyte: So therapeutics along with immunization is the real way to return to some sense of normal. Is that right?

Smith: I think we need both. It would be very good if we at least had a treatment so that when people got sick, we could keep them out of the hospital and from dying. That would really buy us a lot of time to have a good, well-developed, safe and effective vaccine.

Whyte: Why haven't we gotten a vaccine for HIV? We have this commitment toward COVID. People have been working 20 years [on an HIV vaccine].

Smith: HIV is just such a different virus. It has so much more genetic mutability and mutates so much better than coronavirus. I do have some skepticism about coronavirus vaccines. I think that maybe the first generation will work a little bit, but not very well. They may have some duration problems, which is also what we see with HIV vaccine issues.

Whyte: Why do you have that skepticism?

Smith: Because I know that in regular coronavirus infections, our immunity wanes pretty quickly. The other thing is that people who don't have severe SARS-CoV-2 infection — so they don't get COVID and are asymptomatic — we don't see them mounting much of an immune response at all.

I'm not sure how a vaccine that basically introduces some viral antigens in there to stimulate an immune response can really generate a durable immune response. That's what I'm worried about.

Whyte: Dr Smith, I want to thank you for taking the time today to help educate us all about what's happening in terms of therapeutics, especially in relation to vaccines. Hopefully, we'll have the timeline that you're suggesting.

Smith: Yeah, I really hope so. Thank you so much for allowing me to come and talk to you.

Whyte: I want to thank everyone for watching Coronavirus in Context.

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