Paul Sax, MD, discusses remdesivir, scientific literature in the age of COVID-19, and the pandemic's long-lasting effects on the future of health care.
Segment Description: Paul Sax, MD, clinical director of the HIV Program and Division of Infectious Diseases at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, and a member of Contagion's Editorial Advisory Board, discusses remdesivir, scientific literature in the age of COVID-19, and the pandemic's long-lasting effects on the future of health care.
Interview transcript (modified slightly for readability):
Contagion®: Hi, I'm Allie Ward, editorial director of Contagion®. I'm here today with Dr. Paul Sax, the clinical director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital, and professor of medicine at Harvard Medical School. Dr. Sax, you’re a longtime friend of Contagion®. Thank you so much for joining us today to discuss COVID.
Paul Sax, MD: Thank you for inviting me.
Contagion®: First of all, how are you doing? Can you tell us a little bit about what your day-to-day has been like throughout the last couple months of quarantine?
Sax: Like all infectious disease specialists, our days have been pretty much consumed with COVID-19 and the response to it. Unlike some other specialties, before the surge happened in the United States, we were all kind of walking around with butterflies in our stomachs and then, when it started happening, we of course were front and center in the response. Managing that has been challenging and has been gratifying and has been frustrating all at the same time.
Contagion®: We're a few weeks out from all of those remdesivir data dumps. What are your thoughts on remdesivir as a potential therapeutic option for COVID?
Sax: That's a very important question and, I should say, that there were some “data dumps,” as you put it, but the most important data we haven't yet seen in full, which is the controlled trial of remdesivir versus no remdesivir in moderate to severe disease, [where] the announcement came from Tony Fauci and the National Institutes of Health that they had decided to stop the study early because of a benefit that was seen in the remdesivir arm. Now, it was a modest benefit. It was a few days of a more quick recovery, but if you think that there might be some people who respond better than others, that was enough for them to think it's worth stopping it. I always have to remind people that it was a Data Safety Monitoring Board that made the decision and they have access to all the data that we haven’t seen yet. So there's that information still to come.
I would say that there was a negative study from China that didn't accrue its full patient numbers because the incidence of disease stopped increasing in China, so it was actually good news that they couldn't accrue it, but still, we didn't get full information. It ended up being a negative study. And then I will say that many of us are working at centers that have a lot of remdesivir treatment going on and one gets sort of a clinical Gestalt about the drug that that is at least probably somewhat anecdotal, I confess, but, it does seem to be helping some people and especially if it is started before they're too sick.
Contagion®: Switching gears a bit, the US Centers for Disease Control and Prevention (CDC) recently put out a commentary on symptom-based strategies for discontinuing isolation for persons who had COVID. One of the things that was mentioned in the commentary was that, as of its writing, replication-competent virus has not been successfully cultured more than 9 days after the onset of the illness. Can you walk us through that finding and explain what the significance there is?
Sax: One of the key challenges with COVID-19 recovery is that certain individuals, for whatever reason, continue to test positive with positive RT-PCR of the nasal pharyngeal swab for a long time, even after they've completely recovered, and that includes not just people who were seriously ill, but also people who had moderate or mild illness. In those people who have persistently positive tests for a long time, there's a debate among us infectious disease doctors and among immunologists, is are those people capable of spreading the virus onto others? It's really not known so what CDC tried to do is it tried to take those persistently positive cases and see if they could get replication-competent virus, and they were unable to do so.
I always look for good news and everything, and so let me try to find some good news in this. It's possible that what these PCR tests are detecting is just fragments of virus rather than actual virus that can be transmitted to other people. Now, it doesn't change health care systems making recommendations like they want people to test negative before returning to work. That's certainly very common in most hospitals now, and I understand that, but it at least gives us some hope that some of these persistently positive tests don't represent actual contagiousness. I got to use the title of the magazine in my response.
Contagion®: Bonus points there [laughing]. Throughout this pandemic, we've been receiving and consuming information at breakneck pace. A lot of that is due to the way that data are being released and interpreted with preprints and non-peer reviewed articles getting out and picked up by the mainstream media. What is your take on how this COVID-19 pandemic has affected the flow of scientific literature?
Sax: The flow of scientific information has been massive and everyone uses the same analogy, which is “trying to drink from a firehose.” But I get tired of using the same analogy, so I was having a conversation with one of the best science reporters out there, Helen Branswell, and she's Canadian so she said, “I don't want to use that metaphor.” I said, “Well, what?” She says. “It's like Niagara Falls, you know, that's Canadian-American…it's like trying to get a glass of water from Niagara Falls.” That's what it feels like sometimes. On the plus side, it means that the information is being shared very rapidly. On the minus side, it means that non-peer reviewed information, some of it probably false, is getting out there and can be seized upon. Nonetheless, there have been some very important reports that have come out of preprints and one of the early ones was about asymptomatic viral shedding in people in Germany and that ended up being quite important for our understanding of how to protect people going forward. So, it's not an all or nothing thing.
One thing I do wish is that now that we have this remdesivir treatment signal on our radars, that that becomes quickly a standard of care that we can give to people so that other interventions can piggyback on top of that, so it's not just remdesivir or nothing because it's clearly not going to be only remdesivir that's going to get us out of this sometimes very serious disease.
Contagion®: Definitely, it's a good point. We're by no means out of the woods here; we're just at the very beginning. What do you hope that the infectious disease community of clinicians can take away from dealing with this type of experience?
Sax: One major thing is to recognize the primacy of public health in protection of our society. Paying for public health isn't popular because when it does its job well it's completely silent and in the background. But all one has to do is look at the state we're in right now in the United States, leading the world with new cases, deaths related to it, and realize that lacking a strong public health infrastructure has really put us behind in managing this huge outbreak. It's ironic that the countries that actually experienced SARS particularly in Asia, were much better prepared for this than we were. If you want to look at a sort of textbook example, look at Taiwan, which, of course, experienced SARS and so they set up this response to what they assumed would be another pandemic, and they were so well prepared that they really have not had much of an outbreak there at all. And then there have been some other shining lights, Singapore, South Korea. As soon as something starts to flare up, they move in, test, and isolate and get it under control. We have not yet been able to do that, so I think that's one message that we infectious disease doctors have to state loud and clear is that the public health response, [and] infrastructure has to be really sustained.
One other one, which is more personal, is that, the way that health care is financed in this country is predominantly based on procedures and based on doing things rapidly, and neither one of those things is something that infectious disease doctors do. We're very careful in our deliberations and our assessments, and we don't do any procedures at all. As a result, we kind of have been undervalued in the American health care system. I hope that this corrects that because if anything brings up the importance of infectious disease especially, it's a global outbreak like this.
Contagion®: Absolutely. Do you see any other long-term effects of this on the health care system in general, whether it's an increased reliance or emphasis on telemedicine or having those infrastructures in place?
Sax: Yes, it’s going be totally transformative and end up being one of these things that developed quickly because it had to. When we realized that people didn't want to come to the hospital for their outpatient visits, and they still needed to communicate with their clinicians, then telemedicine suddenly became available. Now we have to convince the payers that it's worth paying for and, if not, then they're really not responding to the current needs of the patients who need health care. So that's one thing.
Other things that have to change—we can't have crowded waiting rooms anymore. That's really not safe. We can't have people who are sick mingling with people who aren't sick in those waiting rooms. We have to rethink our use of masks in public for now. That's something [where] a lot of us were wrong and we didn't think that masks were going to be helpful in preventing the spread of this virus. But it turns out that yes, there are people who are asymptomatic and shed this virus and wearing masks for those people probably does prevent spreading the virus. So all kinds of things are going to change. I don't think we're ever going to go back to the way it was pre-COVID-19 100%. I do hope that there will be a diminution in the number of new cases and we'll have some partial return, but it's not going to happen quickly. Another overuse metaphor: This is going to be a marathon and not a sprint.
Contagion®: Dr. Sax, is there anything else that you would like to add?
Sax: Just that last message that people shouldn't lose hope but they also shouldn't expect things just to immediately be back to the way they were. It's unrealistic to expect us to suddenly go back to before we had SARS-CoV-2 circulating in our community is that virus, while predominantly dangerous to the elderly and people with comorbidities, can occasionally cause very severe disease in young people too. We have to be aware of that fact and not move too quickly.
Contagion®: Dr. Paul Sax, thank you again for joining us today and thank you so much for the work that you're doing.
Sax: Thanks for inviting me. It was nice chatting with you, Alexandra.