COVID Webinar Series: Transcript of session with Warner Greene, MD, PhD

KRIS REBILLOT: Welcome.

WARNER GREEN: Thank you, Kris. Pleasure to be here.

KRIS: Yikes. Are you surprised by the rising rates?

GREEN: Well, we are not in a good place. The infections are spiking mostly through the South and the Southwest, even here in California increased numbers of infections. Clearly, a lot of this relates to opening prematurely and opening poorly, really, with the lack of social distancing, the lack of masking. You know, we just can’t go back to normal… this virus.  We may be tired of the virus, but the virus is not tired of us.

KRIS:  The CDC broadened its warning about who is at risk. Younger people with certain health conditions can become seriously ill. What do we know now about the virus that we did not know at the beginning?

GREEN: Well, we know it’s a very serious infection. While some people it’s like the common cold, this virus has the capacity to kill and to kill with high efficiency. These… you know, hypertension, diabetes, obesity… there are a number of risk factors… as well as lung disease. I think all of this is telling us that there is a significant endothelial function… an endothelial property that all of these diseases damage or effect the endothelium. And I think this virus, that we’re going to see an intimate relationship with this virus with endothelial cells, as well.

KRIS: Those are the cells that line our organs.

GREEN: Particularly the vascular system, is what I’m referring to, the… and we know that this virus has a real propensity to elicit clotting in both the arterial and the venous system. I’m… you know, how it does that is one of the things that my lab, along with Dr. Katarina Akassoglou, that we are trying to understand how the virus triggers the clotting cascade.

KRIS:  There are young people and older people coming down with strokes from this.

GREEN: Correct. Yes, and young… you know, a lot of young people having strokes, you know, just out of the blue with this virus.

KRIS:  Papers out that the virus short-circuits our immune system by depleting T-cells. How does the virus impact our immune system?

GREEN: Well, in think that… we have no immunity against this virus, so when the virus enters our body the only thing that determines the natural history of that infection is our innate immune response, our primitive… it’s a first line of defense. And one of the major factors generating that defense is interferon, and this virus has a way of turning off the interferon response, so allowing it to gain a foothold. And, yes, that the individuals who have the greatest degree of lymphopenia are at the greatest risk of developing severe pulmonary disease, and, ultimately, the acute respiratory distress syndrome.

Now, the whole interplay with T-cells and how antibodies are made, these are areas that are rapidly evolving now, our understanding of them.

KRIS:  Do you think that it will require a cocktail of antivirals and vaccines to really bring this under control?

GREEN: Well, I think that if we had combinations of antiviral drugs that acted in a synergistic manner and we could give those drugs early in the course of infection, then such treatments would be highly effective. Indeed, one could even think about using certain types of drugs that were exceedingly safe as prophylactics. In other words, just the way we use antivirals in HIV to prevent… to giving to people at risk, we can prevent people from getting infected in the first place. That would be wonderful if we had those kinds of drugs for SARS-CoV-2, but we do not at this juncture.

KRIS:  ‘What about the oral polio vaccine? Would it be worth asking my physician for a dose?’ There was actually a story online this morning that somebody is talking about using the mumps, measles and rubella vaccine as a possible step gap to provide some protection. Do you have any take on that?

GREEN: Yeah. Well, certainly this is a... I think your guest, previously, Dr. Robert Gallo, may have spoken about it. I did not see his interview, but he is certainly intrigued and wishes to test the concept that an oral polio vaccine could elicit or induce and stimulate the innate immune response to a point that, in fact, people are more resistant to SARS-CoV-2 infection. I think it’s an interesting concept. I don’t think that it would be restricted just to the oral polio vaccine, as suggested by using other vaccines to try and elicit that response, as well.

KRIS:  What about asymptomatic spreaders?  What percentage of the population out there do you think might be asymptomatic spreaders? It seems like a big issue to me. Is it to you?

GREEN: Yeah, I think that… well, there’s two types of individuals— asymptomatic individuals who will remain asymptomatic throughout the entire course of their infection, and then there are presymptomatic individuals who will ultimately develop some type of pulmonary condition, but prior to developing that, they are shedding the virus. And that is the real… that distinguishes this virus from SARS and MERS, where, in fact, viral shedding occurred late in the course of the infection. That’s why public health measures were able to bring SARS under control. Here, you know, the issue is so key, masking is so key given the asymptomatic or presymptomatic phase of transmission. The only way that we can block people from spreading the virus to others is social distancing, which we see is kind of plus-minus, as we’ve opened back up. Masking does work. It really, really works, and we need to be doing that. That is absolutely essential if we, as a country, are going to get by this infection to the point that we have a vaccine. That will be the ultimate solution. But we’ve got to pull together here and get beyond the fact that, you know, wearing a mask is… it’s not a political statement, it’s a health statement. It’s expressing concern for other individuals. I do not want to infect you, therefore, I’m going to wear a mask, even though I don’t know that I’m infected myself. But I’m going to assume I am, and I’m going to try and protect you. That should be the attitude that we all need to take.

KRIS:  Do you think if older people are concerned about their own risk, would it make sense for them to talk to their doctor about polio, mumps-measles vaccine?

GREEN: Well, these are… well, I mean, I don’t think that… I don’t think that you can find oral polio vaccine available right now. I think it would have to… I think it’s not available, as I understand it. The… and this is unproven. I mean, this is hypothesis at this…

KRIS:  Fair enough, yes.

GREEN: And so I probably… I mean, I don’t know. I think everyone has to make that judgment for themselves. I’m not going out to get vaccinated. I’m using more traditional approaches of social distancing, masking, washing my hands, etc., etc.

KRIS:  It just shows how desperate people are to do the right thing for themselves.

GREEN: Absolutely. And, you know, our… we don’t have a lot to really prevent us from getting infected. And that’s an interesting concept, but I just don’t… I’d like to see some evidence that it really works first.

KRIS:  Talk about this disease, COVID-19? There’s two phases of the infection. How can we understand that?

GREEN: So there… yes, exactly, two phases. The first phase is dominated by the virus and the second phase dominated by the host. So when people initially get infected and the virus travels into the lung, at that point in time, the virus is in control. It’s trying to multiply and replicate, and it’s killing epithelial cells in the lung, which is causing respiratory distress. At the point when people get so sick that they need to go to the hospital, that, in fact… they have now entered the phase of the disease that is driven by the host. And now the host is mounting an overly zealous response against the virus, rich in inflammation, and this leads to what’s called a cytokine storm, and, ultimately, to the acute respiratory distress syndrome. So this is very characteristic of many viruses, of coronaviruses, in particular, that they elicit this host, that, in fact, the final phases of the disease and the pathology is driven by the host, rather than the virus, itself.

KRIS:  Do we have any understanding of why this virus is so very infectious?

GREEN: Well, it has… we know now that… in contrast to SARS, that it has a much higher affinity for its receptor, the angiotensin-converting enzyme 2, it’s the… ACE2 is the receptor, and compared to SARS, it binds with about 10 times a higher affinity to that receptor. I the… it is… I think that makes it more transmissible between people. And then, of course, there are the individuals who are super shedders, that have high viral loads when they’re asymptomatic and spreading the virus quite effectively. This virus may… a lot of the spread of this virus may be seeded by super spreaders.

KRIS:  Were you surprised that we have not received the summertime lull that some people were thinking that we might get?

GREEN: Yeah. If you look at the coronaviruses, though, about half of them show seasonality and the other half don’t. In fact, summer colds are often caused by the circulating coronaviruses that cause the common cold. And I had hoped that we would get a respite, but it does not appear that’s the case. I mean, you know, kind of the celebrations around Memorial Day… I watched with great trepidation the many celebrations of people. It’s like, ‘It’s over. It’s over. The virus is, I mean, no longer a concern. We’re out. We’re free. We’re no longer sheltering in place.’ And, you know, it was almost predictable exactly what would happen. And, I mean, you know, the United States has… you know, we have not handled this virus well. If you… if you… we have the second highest per capita infection rate in the world. Only in Brazil, which is in the midst of kind of the first massive phase, has a higher infection rate than us. In contrast, Germany, Italy, France, all of these countries have infection rates which are 10 times lower now. Now, and being second in the world right now, we could well be first with the surge that’s occurring through the South and the Southwest now, for sure.

KRIS:  Do you think the window has closed for having a strategic, thought-out plan to deal with this pandemic in this country?

GREEN: Well, I think the ultimate solution is a vaccine. And there, the news is so far good. We have three companies moving into phase two/phase three efficacy trials. Moderna in July, Oxford and AstraZeneca in August, and Johnson and Johnson in September, and others… you know, many, many others that are closely following thereafter. We’re going to need a… we’re going to need four, five, six different vaccines, and all manufactured at scale, in order to vaccinate the billions of people who are going to need the vaccine. And I just hope that this does not become the same kind of political... I hope that this process is as equitable and as efficient as possible in terms of vaccine distribution, although I worry that it may not be.

KRIS:  I understand that your efforts are really focused on coming up with pan corona antivirals. Talk about that.

GREEN: Well, yes, we’re interested in inhibitors that would work against all of the coronavirus family members. It’s pertinent to note that there have been at least three major entries of coronaviruses into the human population since 2003—SARS, MERS and SARS-CoV-2. And then of course the respiratory viruses, four of them. I think two of them have entered the human population relatively recently. So this is not a rare event, that coronaviruses are transmitting from their animal host, usually through an intermediate… t starts out in the bat, and usually through an intermediate host, some type of animal. In the case of SARS, it was the civet cat. In the case of MERS, it was the dromedary camel. We’re not sure about SARS-CoV-2 yet in terms of whether there was an intermediate. But it makes its way into the human population with some regularity. So we can anticipate that in the next 10 to 20 years, we’re going to see other potentially pathogenic coronaviruses.

So now is the time to actually be creating antiviral combinations that affect not just SARS-CoV-2, but also getting ready for the next transmission. And so that we are looking at conserve parts of the lifecycle of the coronavirus that would be… that where effective drugs would block the entire family, the variances…

KRIS:  I understand you were looking specifically at that spike protein that’s on the coronavirus. We all see the pictures of it now. I think everybody recognizes the pictures of the coronavirus with those spikes. So what are you trying to do with those…

GREEN: Aren’t they red?

KRIS:  They are red. What are you trying to do in relations to those spike proteins?

GREEN: Well, the spike protein has two parts, one it binds to the… one part binds to the receptor and a second part after the variant is taken into the cell via the endocytic pathway into vesicles. And then once it gets into what’s called the late endosome or lysosome, that’s where it fuses. That’s where it melts its membrane with the membrane of the lysosome and actually escapes into the cytoplasm. We’re trying to block that fusion step. And that fusion domain is conserved amongst almost all of the coronaviruses. So if we can come up with a fusion inhibitor against SARS-CoV-2, it should be active against the other coronaviruses, as well.

KRIS:  And then I understand you’re looking at some FDA-approved drugs as potential antiviral therapeutics. What’s that about?

GREEN: So we certainly… we’re not alone in this. In fact, a group at Sanford Burnham in San Diego screened what’s called the ReFRAME library, which is the collection of all of the FDA-approved drugs, as well as all drugs that were shown to be safe in humans in phase one testing. And they were able to identify about 30 different drugs that are used for other diseases that had antiviral properties, that were able to block the replication of this particular virus. And now the question is can we combine those drugs and make even more synergistic… can we make a synergistic therapy? Could we combine one of those drugs with the fusion inhibitors that we’re coming up with and see some type of synergy, as well?

For example, Remdesivir, which we all know, unfortunately, Remdesivir is only administered intravenously… it’s the Gilead drug... it can only be given intravenously.  And so as we were talking about earlier, what you would really like to be doing is getting Remdesivir before people ever come to the hospital in the first place, when the virus is in control of the pathology. So we need drugs… for example, if they could come up with an aerosolized form of Remdesivir, or a subcutaneously administered form of Remdesivir, that would be incredibly valuable, because you could use that as an outpatient. And Remdesivir is a drug that should have activity against almost all of the coronaviruses. We know it’s active against SARS, we know it’s active against MERS because it’s affecting a common… a key RNA… the way that the virus reproduces itself.

KRIS:  You’re also working on a project with Melanie Ott, where you’re looking at organoids, lung organoids. What’s that?

GREEN: Melanie has developed a lung organoid system and we are very interested in how… what’s the mechanism by which this virus kills the lung epithelial cells, the Type II pneumocytes, the cells that are primarily making this refactant [?] in our lungs. We’re interested in how that killing occurs and what kind of program cell death pathway is activated. And so we will be using lung cell lines to begin with, but then once we have kind of… get data there, we’ll then translate it into the lung organoid system that Melanie’s laboratory has developed.

KRIS:  So having organoids, I would think that’s a much better model than looking at just things in a cell in a dish, right?

GREEN: Yeah. Well, these are in a dish, too.

KRIS:  I understand, but they’re more complex. They’re the tissue right?

GREEN: Yeah. They’re much more… they are a much better representation of the actual organ in vivo than, for example, cell lines are. So, yes, it’s a clear advance in terms of testing, for sure.

KRIS:  So let’s talk about vaccines. There’s a lot of activity.

GREEN: Yes.

KRIS:  Who are the major contenders? What type of vaccines are likely to be developed? Where is that state of the science?

GREEN: Well, at last count, I think there’s something like 170 different vaccine efforts around the world. And these range all the way from making the… kind of the earliest types of vaccines, where you take the virus, you kill, and you use that as the vaccine. So a killed a vaccine, that’s being developed. There are also efforts to make an attenuated form of the SARS-CoV-2, a live, but attenuated form of the virus. There is… that’s, for example, the kind of vaccine that Sabin developed for polio, in contrast to the killed vaccine that Salk developed.

But more advanced approaches are now looking at sub units of the virus. For example, the spike protein, which we’ve talked about, is a very popular target for vaccine development. Again, the idea being to elicit antibodies, that block the ability of the SARS-CoV-2 spike protein to bind to its receptor, neutralizing antibodies, would be the kinds of antibodies that these vaccines would be aimed to produce.

So I’d say that the spike protein is the target of most of the vaccine development, but, you know, there are broader efforts, as well. Not all of our eggs are in one basket, for sure.

KRIS:  Do you think once we get a vaccine, will it be in one of those baskets? Are we going to need different baskets to respond to COVID-19? How does a doctor decide, or a health system decide, which vaccine am I going to give to my patients?

GREEN: Right. I heard it said yesterday, you don’t necessarily want the first vaccine, you want the best vaccine.

KRIS:  Right.

GREEN: The best vaccine might differ depending on your age. It might be necessary for people who are at higher risk, who are more elderly, they may benefit more from a particular type of vaccine. Whereas, younger people, a different vaccine may be the most effective. I mean, these are all questions that the answers to which we don’t have. But what we do have is an unprecedented effort going into vaccine development. And, of course, these vaccines are being manufactured at risk. So not even knowing whether they’re going to work yet or not, they’re scaling to hundreds of millions of doses of these vaccines in the anticipating, rapid deployment, should they get a strong efficacy and safety signal.

KRIS:  Given that, I know there have been different predictions, , we might have a vaccine by the end of the year. We might have one by next spring. It seems like, for safety and efficacy, there really needs to be a lot of work done on large groups of people so we do get the best and safest vaccine. Are you at all concerned about safety studies, or what’s your idea of when we might actually have vaccines available?

GREEN: Well, I think the speed of safety testing and efficacy testing is somewhat determined by... certainly, efficacy is somewhat determined by how much… where you’re testing. If there’s a lot of virus in the group of individuals that you’re testing, then you can generate an efficacy signal much quicker than if the virus is rare. For example, that was part of the problem with the Ebola vaccine that was developed initially, that they almost got there too late to understand whether or not the vaccine was working because the Ebola epidemic was dying down rapidly. I don’t think there’s going to be any lack of virus in the community, so I think testing will proceed at pace. But you’re absolutely right, we cannot, we cannot cut any corners in terms of safety. And, again, I just want to… you know, I want to make… I think we all should be concerned that there… that this is not a political issue. You know, we are moving quickly to a vaccine, but there should be no connection between the development of this… of effective vaccines and the presidential election.

KRIS:  There was a question that came in about… back to super spreaders. How are they going to be identified? How can we identify them? And then that might lead into the comment about antibody testing. How do we find these people who, unwittingly, are out and about and might be infecting others?

GREEN: Yeah, so if they’re wearing a mask, they won’t be infecting others. That would be good. It comes back to kind of the surveillance testing that we really… and, you know, the… the first line of public defense is that you do widespread testing to identify individuals who are infected and then you contact trace… you trace all their contacts, and then you quarantine the contacts and you isolate the individual who was detected as infected. We are not doing that in a systematic way in the United States. And I think that, to a great extent, that’s one reason that we’re not gaining control of this virus. We don’t know where it is, and it’s wide… it’s undergoing community spread. I mean, we’re going to see, I predict, an overwhelmed hospital system in Florida, perhaps in Texas and in Arizona. I mean, the kind… you know, it may be uglier than what happened in New York City.

KRIS:  Wow.

GREEN: And… yeah, it’s… I mean, the next two to three weeks, in those states, it’s not going to be pretty at all.

We had a second chance. You know, by going into the lockdown, virus decreased in the community. We had a chance to come out of the lockdown by doing a lot of surveillance testing and finding the infected, removing them and their contacts from society, so society could continue to work. But we opened up at a time when virus was still rampant in many… in many states and we opened up in a non-safe way. So we are… you know, we, in contrast to most of the developed countries in the world, for example, Germany, France, Italy… Italy, Italy was hit so hard that their rate of infection right now is .5 per 100,000. And in the United States, ours is 10.7 per 100,000. So 20 times more virus in the United States than Italy. We’re just not dealing adequately with preventing the further spread of this virus.

KRIS:  A question just came in, which is a perfect follow-up. Because there are so many questions about the virus and how infectious it is, what about the opening of schools?   Do you believe that public schools are going to be able to keep students and their teachers safe?

GREEN: Well, I’ve heard interesting comments about this from George Rutherford, who is an epidemiologist at UCSF. And he’s reviewed a fair amount of data now emerging from places like Iceland, I think, Spain, China, etc., and the… for children less than 10 years of age, they’re not heavily infected. The way they get infected is they get infected from their parents or possibly from their teacher. Once infected, they don’t spread it to other classmates, and they don’t tend to bring… because of that, kids are not bringing the virus home with them. So this is exceedingly good news for, you know, elementary schools, etc. Now, the whole thing changes once they reach puberty. Then… you know, adolescents then act like adults in terms of infectivity.

So it… you could make an argument that you could open up schools and the people that you need to be testing frequently are the teachers, and you need to be… you know, and the parents, you know, the parents need to be because they’re the source of the virus that will infect the children. So I think it’s good… if that… that’s not a… that’s not well-recognized yet, but if those data are confirmed, I think that’s very good news for opening up, at least the elementary schools and preschools in the future.

KRIS:  Do you think there’s going to be a surge in the fall.  ‘What can I do to protect myself once people are forced to spend more time inside?’

GREEN: Well, I think there… I think that… you know, I think that we will probably see another surge in the fall, and it will be accompanied by influenza, as well. I think the one thing that everybody can do in the fall to help protect themselves is to get an influenza vaccine. And we won’t have… we won’t by the fall have a SARS-CoV-2 vaccine.

It’s also not… the other point I was going to make is it’s not clear how long the durability of a vaccine will last. For example, the flu vaccine, we have to change it every year to match the virus. It’s circulating. Sometimes we get it right, sometimes we don’t get it quite right. Hopefully, the SARS-CoV-2 vaccine will last for a number of years, but it’s possible that we may have to get vaccinated more frequently. It probably will not be like a measles vaccine where, you know, one vaccination lasts you for a lifetime.

KRIS:  I got a question from somebody who is interested in antibodies. If somebody has survived, COVID-19, hopefully, they have some antibodies. Is that going to impact who needs to get a vaccine, or how somebody might respond to a vaccine?

GREEN: Well, for people like you just described, who have survived COVID and have good antibodies in their plasma, I would… if they are willing, I would suggest that they contact their blood bank and consider donating plasma, which could be a convalescent plasma, which could then be given to people who are really quite ill. The blood banks are coordinating this type of convalescent plasma administration throughout the country. That will ultimately lead to… the fact that there are such antibodies from recovered people, we will ultimately have now monoclonal antibodies from the best of those producing clones of cells, and those will become a very valuable therapeutic. That’s kind of the bridge, you know, convalescent plasma, monoclonal antibodies, all passive immunity, you’re giving passive antibody protection, which only lasts as long as the antibody survives. And then the next step of course, is active immunity, the vaccine.

KRIS:  ‘Who will decide how a vaccine is deployed to the population, and in what order?’

GREEN: That’s a very good question. I would… I would have… well, I would have thought that it’s either going to be HHS, Health and Human Services, or CDC. Those would be my two guesses. Probably HHS will be in the lead.

KRIS:  There was a news report this morning that shows that perhaps the virus is mutating, or that there is a mutation in part of the virus that is making a particular version of it more infectious. There was a question about mutation. Is that going to make it more difficult to find a vaccine?

GREEN: So it’s an RNA virus, and, by definition, the RNA viruses change more than DNA viruses. That said, SARS-CoV-2, and the coronaviruses, they all have this proofreading enzyme, which tends to correct a lot of the errors that are made. So they do not tend to mutate as much as, for example, HIV, or hepatitis C. So that’s good news for vaccine development, that the sequence, while modestly changing, is not radically changing all the time.

KRIS:  We are getting some questions from folks about how to live in this time of semi-opening up. I want to talk to you about how your own family made a decision, facing risks and what’s going on. Talk about that, because I love the thought process that went into it.

GREEN: Right. So I have two daughters, and three granddaughters. One daughter is a nurse at Lucile Packard Pediatrics, and the other daughter works in Los Angeles. And so we have not seen our grandkids in person for many months. And it was a special occasion, a very special birthday for my wife, and so we decided that we were going to meet halfway between Los Angeles and San Francisco, we would rent a house. And my daughter got tested, her husband got tested. Also, the LA granddaughter was about to go back to preschool, and so we thought it was a good thing to get together before she went back to preschool. And so we got together and we decided… you know, had been following the… had been, you know, socially distancing, not exposing ourselves, etc., so… and Alison, who was kind of the wild card, because of the nursing, was tested negative, so we decided to interact normally. And that was, you know, a calculated family decision that we all undertook, and it was the most wonderful weekend imaginable.

But now we’re back… now we’re back to, you know, the social distancing, because, you know, the girls are seeing other kids a little bit… you know, people are starting to form pods. And so their social network has expanded, but then they’re trying to stay within that pod. But Peggy and I… as the pods have increased, Peggy and I have become more conservative again in terms of our interactions with the grandkids.

KRIS:  ‘If we hire a live-in nanny for newborn care, how long should she and us be wearing masks when interacting with each other, and when she takes care of the baby, assuming either one of us could be asymptomatic and spread the virus for a while?’

GREEN: So, in general, the… I mean, you know, the quarantine period for someone who is of unknown infection status is 14 days. And that’s set because 95%-plus of all symptoms will develop within… people who are going to become symptomatic will do so within that period of time. It’s not perfect, but it’s pretty good.

So, now, it’s a live-in person? You said to live in. Okay. So I think certainly, you know, quarantine…  I mean this type of 14-day quarantine can now be replaced by testing. You can test the individual. If they test negative, then you don’t really need to kind of do this 14-day. Now, the… you know… so that’s what I would do if I… I would have… I would get everybody tested. If everybody’s negative, then you’re good to go. But that only works to the point that those three adults with the baby, that they continue to socially distance themselves, you know, and observe appropriate public health measures. Otherwise, any one of them could become infected from someone on the outside.

KRIS:  So I got a follow-up to our discussion about schools. Somebody would like to know how much greater the risk is in a young person who is in puberty and adolescence, and should these kids and teens be kept out of school longer? So do you have any sense of how the schools should deal with older kids?

GREEN: Well, I think high schools are going to be different. I think they’re… I think it’s going to be more difficult. But, again, you know, I’m not an expert in terms of public education and how best to respond to this. I do know that… I think the homeschooling, from what I understand, is not going well, that it’s very difficult. And I think that we need more creative approaches to the education of our young children, because this could go on for… you know, we could be in this situation for an indeterminate period of time. I mean, I hope that the vaccines are fantastically effective and are deployable within a quick period of time. But, I mean, in all reality, you know, we probably are looking at another year of virus circulating in our communities, and having to do some type of public health interventions to keep that virus down. And I think it just emphasizes we have not figured out how to live with this virus. We’re not very effective at it. Other places in the world seem far better at it than we do, but we need to get our act together. But I don’t know how to answer the high school question.

KRIS:  Somebody asked a question about the experience in Sweden. So Sweden did a thing where they kept everything pretty open, and they were looking for herd immunity. How’s that worked out?

GREEN: Not good. They’ve had a lot of… I was just looking at Sweden. Infections are on the rise in Sweden again. They had a dip, and now it’s on the rise again. They’ve had… if you compare it to Finland, Norway, and Denmark, a lot of excessive death. In fact, the public health minister whose idea this was to try and create herd immunity, he ultimately had to, you know, step away from that position and to implement, you know, less… you know, some public health interventions had to be made. Also, unfortunately, I mean, they didn’t come anywhere close to herd immunity. I think that their antibody positivity is somewhere around 20% in the population. I think that’s what I read.  So that was a failed experiment.

KRIS:  Among this nightmare, has there been an silver lining for you, personally, or the field, in general?

GREEN: Well, I think that… I think that, as a virologist, I could never have imagined a virus bringing the world to a full ground stop, like SARS-CoV-2 did. You know, when SARS-CoV-2 broke out, when COVID-19 broke out in China, I had… initially, I thought it’s going to be like SARS. There’s going to be a few thousand. You know, but then it grew and it grew. And then it jumped countries. And then it spread to Europe. And, well, you know, we’re facing the largest public health challenge in the last 100 years, since the great influenza, or the Spanish flu.

So what it… the one thing that’s been gratifying is to see the incredible scientific collaboration that has occurred. Scientists really, you know, kind of dropping… you know, really working in ways that are not in their own self-interest, but in the interest of progress in the field. And that’s been very, very satisfying.

KRIS:  Given the current lack of coherent leadership, is there anything in addition to wearing masks that people can do now, either for themselves of their fellow citizens. Should everybody go out and get tested?

GREEN: Well, I think the… again, the… wearing a mask in key. I mean, I think many countries in Asia, they faced respiratory viral outbreaks and masking in a routine part of their response, and they… for example, South Korea brought it under control, Singapore, Hong Kong, you know, and masking was a big part of that. Unfortunately, masking now has become a political statement in the United States. And, I mean, we have just got to stop that. We’ve got to… everyone’s got… if there was anything that should have brought this country together, a common threat, it was this virus, COVID-19. And I hope that… I hope that at some point we can stop this blue versus red issue, and really face this virus in a consolidated, unified manner. But that requires… the requires leadership at the top to do that.

KRIS:  I always get questions from folks who are following the rules, but people also want to know what they can do to give themselves the best shot of doing well should they become infected.  What should people be doing?  Is there anything that people can do?

GREEN: Well, if I… if I got… if I got infected, I know the first thing I’d do is try and get subcutaneous lambda interferon. There’s a trial underway at Stanford. I’d try and get enrolled in that trial, for sure. You really want to be giving the antivirals early in the course of the infection.  Unfortunately, you can’t give Remdesivir because of the intravenous, and, also, there’s very little Remdesivir around to be administered. It’s very difficult to synthesize it.

So, no, there’s not a lot, there’s not a lot that we can do. You know, the studies with dexamethasone were promising, but, of course, that’s modifying the host response, that’s for the very seriously ill. But that was good news, that dexamethasone works. And I think we’re going to have a variety of additional antiviral drugs that are going to be coming… becoming available, are… identified and then become available. I think there will be some repurposing.  But, for example, the Favipiravir, which is the Fuji Film kind of version of Remdesivir, that can be given orally. And so it would be wonderful if that drug actually gets better developed, tested, and deployed.  But, right now, we don’t have a lot to give.

KRIS:  Marin County is home to San Quentin. There’s 832 active COVID cases at the prison. Is that a danger to the larger community?

GREEN: Yes, to the extent that the guards become infected and the guards introduce it into the community. But, you know, congregate living situations, like nursing homes, prisons, businesses where people work in close proximity, like meatpacking industry, etc., I mean, some of the… also, I’ve seen some of the Amazon warehousing… warehouse workers have become infected. These are all situations that require special interventions. Like in the nursing homes, for example, the State of New York is now testing every nursing home worker every week to make sure that they’re negative. And they know that all of the people in the nursing home are negative. So you’ve got to take special approaches in those types of congregate living situations. And, yes, Marin is kind of a hot spot right now, but it’s mostly driven by the prison outbreak.

KRIS:  The Buck’s focus is on older adults. Is there any sense of why this virus impacts older adults, that they’re more at risk for serious complications?  How is that risk factor going to work as far as upcoming vaccines and potential antivirals?

GREEN: Well, I think that older people, in general, are more likely to have the risk factors associated with more serious disease. They may also have a less… their immune response… a certain degree of senescence in their immune response. Although you might think that that could help in the situation when… during the host phase of the disease, you would think that a weaker immune response might mean less chance for cytokine storm, etc. But that doesn’t seem to be the case. Yeah, I think that it’s probably just an overall kind of lack of innate immunity, or diminished innate immunity, so the virus can get the foothold.  You know, that would be my guess.

KRIS:  When you talk to your colleagues and collaborators, as far as scientific possibilities, what are you mostly excited about?

GREEN: Well, I am very confident that science will prevail. I do believe that we’re going to have combination antiviral therapies, and I think we’re going to have safe and efficacious vaccines. But I think that all of that will require some time, and that’s the issue. Can we stay healthy? Can we, as a country and as a world, stay healthy and learn to live with this virus until we can get rid of this virus or have ways of really managing it?

So I’m impressed with the amazing focused effort that’s going on around the world. I don’t think we’ve ever seen science so squarely focused on a problem like this as we are seeing now, and it’s going to yield great fruits. We just… you know, we need the gift of a bit more time. So people need just to… you know, do not… do not yield to COVID fatigue. Hang in there, and science will get us through this.

KRIS:  Thank you.