Pushkin from Pushkin Industries. This is Deep Background, the show where we explore the stories behind the stories in the news. I'm Noah Feldman. Research into the novel Coronavirus is happening and being published or sometimes just press released at breakneck speed. Every few weeks, we hear about a possible new breakthrough or a potentially interesting avenue of research. But often that breakthrough it turns out to be too good to be true, or to have less effect than we might have imagined.
To help us make sense of the latest about the novel coronavirus, which studies to watch, which studies are too soon to interpret, and where we are in the progress towards a vaccine, We're joined by doctor Sad Omer. Doctor Omer is a professor of infectious disease and epidemiology at the Yale School of Medicine and at the Yale School of Public Health. He's also director of the Yale Institute for Global Health. In short, he's perfectly qualified to talk
about these questions. So thank you so much for joining me. I'm very grateful. I wonder if we could begin with some of the latest publicized developments in therapy. There's a large randomized study out of the UK, which we only see in so far in press release form, although we're getting used to that, involving the use of the steroid dexamethasone. What is your takeaway from that study. It's a very encouraging study for several reasons. First of all, from the protocol,
it seems that it was a well conducted study. They showed an impact on mortality, not on everyone, but those who were on vents. The third thing is that it's a widely available drug. So whenever you are dealing with these public health emergencies, one concern, one major n is equity. At least in the initial few months after a drug is evaluated successfully or it comes out, etc. You're really
concerned about getting that to the most vulnerable. Since this is a widely used drug already, we have broader availability. So that's the good news. The caveat, as you pointed out, is that all we know at this point is a press release, a press release from a credible group. But look, I would like to see at least data, maybe not a full flash paper, but they worst probably somewhere some discussion at their data Safety Monitoring board or somewhere where
they presented those slides. At least share those slides. Now. I understand that there's a lot of time pressure on investigators, but if the data are good enough to be shared publicly in a press release, they should be good enough
to be shared more broadly. The effect on mortality on deaths reported in a press lease was a one third reduction for those people who were so sick that they were on ventilators, and I believe a one in five reduction in deaths for those who were sick enough to be on oxygen but not oxygen delivered via a ventilator. And then for those who were very sick and in the hospital but we're not on oxygen, they reported no effect. Obviously, I'm asking you to reconstruct something that's not so simple
to reconstruct. But why would one have expected those sorts of results specifically from this treatment. Yeah. So, look, we are learning about the disease as we go along, and sometimes what works in terms of treatment tells you as much about the disease as it tells you about the
intervention itself. But in this case, and you know, these results combined with our previous current understanding of what's happening with the patient with the individual after you get the disease, is that there is this maladaptation and then this exaggerated response of the immune system. And so the contrast is higher when you have an intervention that is attacking the condition by dampening broadly the immune response at a stage
when it's exaggerated. So that contrast would be highlighted in more severe patients because, for example, the cytokine storm is happening in more severe patients, So if you're attacking that, that's where the contrast is. So that would be in line with these results, and that's because steroids are broadly speaking anti inflammatory, but maybe going on in these most sick patients is some kind of the cytokinde storm, which
is a kind of exaggerated immune reaction, exaggerated maladaptive. So it's not just the quantity of the immune response, but the type of immune response. But but essentially focusing on the type of response and the quantity of response and sometimes dampening it broadly speaking can have these benefits. So
that would explain it. So if I just to make sure I'm understanding you correctly, because the sicker patients actually benefited proportionally more from the steroidal intervention that provides some indication that at least in those very very sick patients, what's going on is the kind of thing that might be responsive to steroids and therefore fits the theory argued for by some of your colleagues at Yale and others
of the cytokind storm. Yeah, exactly. Let me ask you about this large genome wide association study that's being reported on in Europe. Again, I think we don't have the full final paper yet in which an argument is being made for an association of blood type, surprisingly enough with probability of suffering from COVID, not exposure to the virus, but suffering from the disease if you are exposed to
the virus. And then there's it's not the blood type itself, according to the theory, at least, it's a some set of genes that are associated with the same gene area as the blood type. If I'm getting it right, say a word about that place. From my perspective, it's too early to say anything definitive about this. It's a signal generation. I think there needs to be a lot more work
to look at. First of all, if the signal is credible because a lot of times when you do these observational studies in sick patients, you're not able to match appropriately you control for underlying confounding and so therefore that's one of the reasons we would like to see more detailed data, etc. To figure that out. I think this one is too early to say anything definitively. I think it's certainly something that needs to be followed up that
could have further implications. So I would put it in the bucket of signal generation more than or hypothesis generation
more than anything beyond that. It was fascinating to me because it reminded me of some of the other high profile GA genome white association studies, where you know, the researchers look potentially at hundreds of thousands in some cases of people with some condition and then they just literally mind the data, which is what scientists we're supposed to not do in the bad old days or maybe the good old days, and they say, well, we're minding the data,
and here's what we see. You know, these are these associations that we find in the data, and therefore they must have some effect, and now let's try to figure out what that effect is it's sort of the opposite of what we were all taught. The scientific method is supposed to be, and yet it has caught on as a real methodology, and it often yields fascinating things. But of course there's some statistical reason to think that some things should be yielded anyway. Yeah. No, So here's the
interesting thing DWAs. And big data techniques, whether applied directly to biology, to or to other sources of data, give you great power and for a lack of bettle example, you know, i'd quote spider Man, power comes great responsibility. Actually Voltaire said it before, but you know, you know spider Man, or actually his uncle Ben said it with more flair. So with this kind of these kinds of tools, it's okay, it's reasonable to apply these tools, but a lot of it is in what you do when you
find something. So if it's taken as a signal hypothesis generation exercise to then do a sort of a hypothesis testing set of studies, this kind of an approach can add value. But if it is taken as hypothesis testing exercise, then you get into some of those other issues that you mentioned a little bit earlier. Two vaccines are getting very close to trials that are going to tell us probably whether they work or not. The Maderna vaccine RNA based vaccine, and then the Oxford vaccine, which is a
trojan horse vaccine. These are both brand new techniques, neither of which, according to guests I've had here before, has ever generated a successful vaccine that went to market. Yet nevertheless, we're all extremely excited and eagerly anticipating the results. Everyone has some instinct about this. You're in a position to actually have an intelligent instinct. What is your instinct about these possible vaccines? So first of all, I add in a little bit of nuance to these are two Western
vaccines that are two of the more prominent ones. There are a couple of Chinese vaccines that we should keep an eye out for and we should track. So one is produced by the company's Signo vac and then the other one is can sign on. But coming to these vaccines, the Modern vaccine and the Oxford vaccine are some of the earliest vaccines that are being evaluated or likely to
be evaluated in large trials. The Oxford vaccine has an innovative trial design where they had a rolling Phase two three trial where they have already enrolled a bunch of people, not they're not close to their final sample size. And one of the complications, one of the nuance that has been added is that some of the earlier projections of their timeline, as I understand, was based on the incidence in the UK because that's where the main core of
the investigators is located. So that the disease incidence going down seems to have complicated things a little bit. And they are going to Brazil now to recruit, which is very reasonable and this is how it should be done in a pandemic. But the reason I'm highlighting this is, look, this is one of the reasons why we should stay away from predicting that the vaccine will be available in
three months. You can say that it will be available in the near future or the prospects look good, because there are a lot of things that can slow down your development process. But coming back to your original questions, so the main question that these are a new approaches, I think they're based on pretty sound biology. Then there should be in the front line of things where the global community and national programs invest Having said that things
can go sideways you can have unexpected things. So what do we do about that? A First of all, have realistic expectations about the timelines. If they go early, that's great, but we should all have a little bit of humility about our projections, especially for new products. The other thing is we should all hedge our bets. So it's a good approach to have a diversity of technologies, some new,
some old. So having a couple of live attenuated products in the mix, having a couple of recombinant vaccines in the mix helps us even out that risk. And so these are the few implications of having a vaccine program or a vaccine development program that has a few new, novel, innovative products. Can you say something about the two Chinese vaccines that you mentioned, because those have not gotten the
same amount of coverage in the US media. But my understanding is one of them is a live attenuated vaccine, good old fashioned vaccine. Yeah, exactly. You take the virus and you primarily through serial passage through culture, take away the disease potential, but ideally maintain the replication potentials. So that's the live attenuated vaccine. There's another vector vaccine that is also in more advanced stages. So these are the two vaccines that are ahead of the pack in China.
They also seem to have issues in terms of Phase three trials because of the successful control they have achieved in reducing the incidence of the virus in their own population. One of the most important things I think that you just said is that we need to realize that even just running the trials can take longer than one expects. Even if these are great, the durational issue isn't easily
manageable because these aren't challenge trials. No one is being at this point intentionally exposed to stars Covy two virus. There have been people who've talked about the value of doing that. Under the circumstances, I have actually been opened. I understand ethical challenges. I've been sort of opened to the ethical argument that when many people are dying and the economic effects are as great as they are, if there's ever a time for challenge trials where people are
intentionally exposed, this is it. It sounds as though you're not convinced, well, I'm actually I haven't made up my mind in terms of specific challenge trials, And here's the reason why I think they're a legitimate policy option that should be explored. But in order to going forward with an actual challenge trial, I think we need a few more things, and I like the WHO approach, so they issued ethical guidance about if to do it, this is
how you do it. It's not straightforward to do a challenge studies because you have to have a standardized challenge doors for humans, you have to have a more rigorous set of protocols facilities. The ability to do that and the ability to conduct challenge trials is actually way more limited than to do efficacy trials throughout the world. So there are fewer centers in the world that have done human challenge studies. So obviously animal challenge studies are different.
And so one of the thinking that that is there, which is not discussed too much in the public discourse or discussion, is what is the added time gain if you have to take these several steps that require you know, some time to iron out. Having said that, you know, developing it as a parallel policy option is very reasonable, but it should be done with not just policy discussion,
but detailed call discussion. I want to ask you about asymptomatic transmission as sort of our last topic of conversation. I guess the question that I'm really interested in is we all understand that there's droplet transmission from coughing sneezing. We also understand that there is presumably some sort of aerosolization transmission where the droplets are much much, much much tinier. I think a lot of people are trying to figure out how they should think about those two aspects of
transmission and what it means for masks. So within the symptomatic they can be sort of different modes of transmission. It could be from surfaces or full mites, mediums, large sized droplets as well as small sort of aerosols. Although that the data are being generated, there's a few things to keep in mind. First of all, the classifying the type of the size of droplet and the probability of
something being aerosolized versus not so. Hanging out in the air for some periods and sort of transmitting through air is different from aerosualization, which stays much longer in the air. We do know that the risk of aerosolization is way higher in some higher risk procedures such as intubation, enduring medical procedures, and even you know specimen taking is likely to be especially in Nize with angel swabs, etc. So therefore healthcare workers need to have PPE for some of
that stuff. The good news is if you have good personal protective equipment in healthcare settings, even with aerosolization, we seem to have fairly low transmission wherever PPE was available,
So that's setting that aside. So now for mass transmission, what you're dealing with is a surface paced versus you know, these droplet transmission, which is not quite a rasalized but these droplets can travel, you know, reasonably far beyond six feet sometimes, and those droplets there is evidence, or again it's not definitive evidence, that you decrease the probability of that spread if you are wearing masks, but the effect
size on an individual level is relatively modest. So the thinking is because it's not a very intrusive intervention, if you have masks compliance with mask wearing, you decrease the probability to an extent that you can see a substantial population impact. That last point is fascinating and one that has not I think been fully stated, partly maybe because people in the public health space don't want to state it as explicitly as you just did. So let's just
go over it for clarity. What I hear you to be saying is that although the data on masks, not in the hospital context but in the public context, are not necessarily that definitive, and although the effects actually might be relatively small, there's a kind of public health judgment that says, well, it's very low cost for everybody to wear masks, and let's insist that people wear them, in fact, regulated by law in many places, including where I live
in Massachusetts. And then we think that cumulatively, that is likely to have a harm reducing effect, and the theory is sort of that there's not that much downside. If that's the case. I do think there's a little bit of subtlety there, because it involves a value judgment about how low cost it is to wear a mask, and I think that may vary from person to person, and there are regional variations and how people feel about it, There are cultural differences in different places. So I'm wondering
if you could just say a little bit more on that. Yeah, no, I agree, And so that's one of the reasons why public health agencies have gone back and forth on this issue. It's not a clear good issue. So there's a nice review by Oxford that try to incorporate all of these things, and they did show that at really high compliance numbers you can have a pretty substantial population level impact. What
level of impact is there? So, based on the fact that a lot of these are assessments from studies that are sort of still evolving in terms of the evidence is still evolving. Because of that, I don't think we can say what is the amount of impact, but there's likely to be some population level impact. But I think you're right, we need to have some nuance in the messaging. Thank you very much. I really appreciate your time, my pleasure, and these were great questions. Sud's analysis is crisp, clear
and helpful. First, and most importantly, we should not assume any specific time when we will know if the existing vaccines that are being tested work. Challenges to the testing process are endemic at a time when the virus is itself being controlled in many places in the world, and resetting up a protocol in a place where the disease is spreading faster is actually time consuming in its own right. So the fact that it is possible to get trial results sometime in twenty twenty does not at all mean
that we will get those results in twenty twenty. Next, when it comes to new therapies, we need to see more data. It's very promising that the steroidal treatment of dexamethasone is helping to reduce deaths. This is the first therapy we've seen that actually specifically does reduce deaths, because the rim desvere therapy reduced time in the hospital but was not shown statistically to reduce deaths. So that's promising.
But we still do not have publicly released data. What we have rather is a press release from a reputable group, Sad says. Sad also reminds us to keep an eye on the vaccines that are coming out of China, including a traditional style vaccine with an attenuated form of the virus, a topic to which we may return in a future episode. Last, but not least, when it comes to masks again, Soad
calls for nuance. He points out that some studies suggest mild benefits of mask wearing, which can be magnified through the population if there's very very broad compliance, and that public health officials think that is worth doing, in part because they judge that the wearing of masks is not, in fact a high cost public intervention that raises fascinating issues about the costs versus the benefits of mask wearing. I guarantee you we will return to that issue in
the near future as well. We'll be back in a moment. During the intense last couple of months, we've been so focused on getting you COVID stories that we temporarily paused a segment that we used to have on the show called Playback, where I choose a moment in the news and play it back to you for further discussion. This week, we're bringing playback back, and in particular, we're going to turn our attention where it always goes at the end of June, to the Supreme Court of the United States.
That's the sound of people celebrating in front of the Supreme Court last Thursday, after the Supreme Court ruled that the Trump administration had acted unlawfully when it tried to rescind DHAKA, the Deferred Action for Childhood Arrival's program designed to protect people known as dreamers. From a moral standpoint,
this is a tremendously gratifying decision. Dreamers are about the most sympathetic people you could imagine, And the fact that the Trump administration sought their deportation was again, from a moral standpoint, horrendous. That said, the Supreme Court's decision was
itself surprising on the law. The decision was written by Chief Justice John Roberts, who is ordinarily a staunch conservative, and as the fact that it was a five to four decision shows, there were grounds that a conservative justice like Roberts could have used had he wanted to decide that what Barack Obama put in place, namely the DOCCA program, Donald Trump could remove. Indeed, Roberts typically has a rather
expansive conception of executive power. And although we can know with one hundred percent certainty, I would say there's ninety nine percent probability that several years ago Roberts was one of the justices who voted to strike down an Obama program that was similar to DOCA but aimed at parents. So what was going on here? Why did Chief Justice John Roberts choose to leave his conservative allies and join
the liberals to keep DOCCA in place. Sometimes when Roberts issues an apparently liberal decision, it's clear that what he's doing is trying to preserve the appearance of legitimacy of the Supreme Court by avoiding a scenario where the public would think of the justices as basically partisan. Roberts understands that the public knows that the Supreme Court justices have different ideologies. What he doesn't want is for the public to think that the justices vote based on the party
of the person who appointed them. That may explain Roberts's vote not to entirely strike down Obamacare, the Affordable Care Act some years ago. In the DACA case, however, Roberts's motivation seems to have been somewhat different. What seems to be motivating Roberts is a kind of disrespect for the Donald Trump administration's unwillingness to cross its tees, dot its eyes, and follow the rule of law when it comes to
issuing important governmental decisions. We saw this a year ago when Roberts also provided the decisive fifth vote to reverse the Trump administration's plan to put a citizenship question on the twenty twenty census. In that case, as in the DACA case, Roberts relied on a law called the Administrative Procedure Act, which is the law that gives the federal courts the authority to oversee and review decisions of administrative bodies in order to determine whether they complied with the
pre jurors that the law demands. In particular, the Administrative Procedure Act requires that the government give clear, honest, and accurate justifications and reasons for why it's doing what it's doing, and both the Census case and the DACA case, Roberts ruled that the government had failed to provide those justifications.
In essence, Roberts was saying, taking the action in question was within the general authority of the executive branch, but the executive branch didn't do a good enough job of explaining why it did what it did. This kind of judicial supervision of governmental action is crucial to preserving the rule of law, and it's pretty clear that John Roberts
no longer trusts the Trump administration to do that. To be sure, at the beginning of the Trump administration, Roberts was willing to give Trump the benefit of the doubt. He after all, wrote the opinion in the Trump against Hawaii case, the one involving the Muslim travel ban, in which he upheld the president's authority to issue the version of the travel band that was in play at the time.
What seems to have happened subsequently is that as Roberts has gotten a closer and closer look at Trump's disrespect for the courts and his disrespect for the rule of law, He's decided to take on the role of defending the judiciary, defending the rule of law, and of him making Trump comply. And it may not be irrelevant that Roberts also had to spend a good chunk of his January sitting in the Senate listening to the Impeachment Manager's condemnation of Donald Trump,
precisely for his disrespect for the rule of law. So if you're wondering whether John Roberts has suddenly become a liberal, take it from me. He has not. I expect more conservative decisions from him, possibly even this week or next. But John Roberts has taken up the responsibility of the judiciary to keep an eye on this president, and for that I think everybody liberal or conservative should be profoundly grateful.
Next week, we'll be taking a break for July fourth, but we will see you the week after, and until then, be careful, be safe, and be well. Deep Background is brought to you by Pushkin Industries. Our producer is Lydia Jane Cott, with mastering by Jason Gambrell and Martin Gonzalez. Our showrunner is Sophia mckibbon. Our theme music is composed by Luis GERA special thanks to the Pushkin Brass, Malcolm Gladwell,
Jacob Weissberg, and Mia Lovell. I'm Noah Feldman. I also write a regular column for Bloomberg Opinion, which you can find at Bloomberg dot com slash Feldman. To discover Bloomberg's original slate of podcasts, go to Bloomberg dot com slash Podcasts. And one last thing. I just wrote a book called The Arab Winter, a Tragedy. I would be delighted if you checked it out. If you liked what you heard today, please write a review or tell a friend. You can
always let me know what you think on Twitter. My handle is Noah R. Feldman. This is Deep Background.