Dmitry Isenberg:
Good evening, or good afternoon, depending on where you are. I'm Dmitry Isenberg, president of the Connecticut Alumni Chapter and on behalf of Brandeis University, I would like to welcome to today's webinar. Our webinar will be moderated by Dr. Joel Reich, who is a dear friend of mine and an ex-Brandeis alum. Dr. Reich has many years of experience in the healthcare system, including the department chair, medical director of EMS and later the chief medical officer of one of Connecticut's top hospitals. Over the years, he has presented at national seminars on health, IT, quality improvement, and accountable care among other topics. Currently, Dr. Reich is a healthcare consultant and medical school faculty member. Joel, take it away.
Joel Reich:
Thank you, Dmitry and welcome everybody. We're just going to take about two more minutes to let more people join the program, so bear with us and then we'll jump back in at about 7:0-
Susan Weiss:
Six people.
Joel Reich:
... 3.
Susan Weiss:
Sixty-seven. Wow. There's one MD on here. I don't know any, recognize any names.
Joel Reich:
Well. Okay. Well, welcome and thank you for joining us this evening for what will be a very interesting webinar. We're very fortunate to have two excellent speakers. One, who full disclosure is my sister, Dr. Susan Weiss, who has spent her career working on the coronavirus and is very much in the midst of things going on now across the country and internationally and Ed Fein, who has a wonderful a background as a pulmonologist and critical care physician. Before we jump in, we're going to do a brief poll of all of you, which will help guide the comments by the panelists and guide some of the questions and answers that we do following their presentations.
Joel Reich:
If we can go to the first polling question please. In which region are you living at the present time? I know there's a lot of ways this can be sliced and diced, but at least pick the region that most closely fits where you are, and we'll give you about 10 seconds to respond, and then we will put the results up on the screen. Okay. We just got a chat question about where is the question. It should be showing on your screen presently, but let's not get hung up on this. Let's move to the audience replies to this first poll if we can post those please.
Joel Reich:
Okay, so pretty spread out, about just for people that may be calling and may not see it, the Northeast is about 60% and then the rest of the country is pretty split in 7% to 15% range in each region, and then about 1% is from outside the country. Let's move on to the next question please. A member of immediate family has been diagnosed with COVID-19 infection. Again, just give us a sense of how close people who are attending the webinar have been. Meanwhile, let me just mention, somebody has already started a question, which is great. There is a question and answer box at the bottom.
Joel Reich:
If your control bar for Zoom is at the bottom, it will be there, usually next to the participant's icon and please start putting questions in there and we will get to as many as we can after the presenters. Let's go to the answer on the second poll question please. Four people, about 6% of our audience have family members who have been affected directly by COVID-19 infection, so thanks for responding on that. Let's go to the third poll question please. Okay. When did your area begin government mandated social distancing, and we give you four date ranges. Again, take your best shot at it. We just want to get a sense again of what people's experience has been with the COVID-19 pandemic.
Joel Reich:
Again, don't worry about exactness here, we just want to get an idea. Let's go to the responses on this poll question please. Yeah, so many people again being from the northeast, the two thirds are in the March 16th to 31st period, not surprising, and then a couple of percent not practicing social distancing, which may be in the US, maybe outside, but let's move to the last polling question and then we'll get to our panel presentations. Then just gives us an idea of your background, so my career has been focused in the following discipline. We obviously haven't an it everything, but pick the one that's closest. If you are teaching, either choose education, or pick the area that's closest to what you teach.
Joel Reich:
Again, this will just help us with some of the panelist's comments and how we answer the questions. We'll give this one just a few more seconds and let's go for the polling responses please.
Susan Weiss:
There's some people in...
Joel Reich:
Okay, so actually 27% are in the medical field so that's interesting. Higher than we were guessing, but great to have everybody here. Okay. With that, we're going to move from the polling to the first presentation and that's Dr. Susan Reich Weiss, who is going to present. By the way, I've had the opportunity to see some of these slides because they've been used in national and international presentations, so really top notch information that we're about to receive. Please let me hand it over to Susan now.
Susan Weiss:
Okay, let me go on to screen save if I can find it. Right. Screen save, screen share. Okay. You see my screen?
Joel Reich:
Yup. Just need to go into projection mode.
Susan Weiss:
Yeah, yeah.
Joel Reich:
All set, looks good.
Susan Weiss:
Well, you got the end of my talk there. Okay. Okay, so I'm going to give an introduction to coronaviruses and seeing that there's so many medical and science type people here, I hope it won't be too detailed and too scientific. Okay, so I'm going to start by just showing you coronaviruses are members of a super family called nidoviruses, and they're called this because they generate a nested set of subgenomic RNAs during infection. Nido means nest. These are all medium-sized RNA viruses. They have a lipid membrane around them. That's why they're called enveloped, and they have single stranded positive sense RNA genomes.
Susan Weiss:
The genetic material of these viruses is RNA and not DNA, and they are called coronavirus because they have the so called corona-like morphology. You can see that here in the coronavirus. This is the virus particle. It's really quite simple. It's a very long strand of RNA shown here about 30 kilobases, 30,000 bases. It's capped and polyadenylated, which means that it looks like a eukaryotic or host messenger RNA. There's a membrane and it's complex with nucleocapsid protein and this is an helical nucleocapsid. It's called a capsid inside of the virus particle and around the nucleocapsid is a membrane shown here. The membrane is derived from the host cell when the virus is assembled.
Susan Weiss:
In the membrane, there are three proteins. The spike protein that everyone's probably heard about the spike protein. It's talked about a lot and this spike protein mediates viral entry, binds to its receptor, and mediates fusion of the virus into the host cell. It's an important determinant of tropism of the immune response and of the virulence of the virus or the pathogenesis of the virus. Also, in the membrane are two other proteins called membrane protein and small membrane protein, and all of these proteins play an important role in the virus life cycle, even though spike protein is really the one that people would be talking about the most.
Susan Weiss:
Oh, and then some coronavirus also express a protein called hemagglutinin-esterase. That's in the virus particle as well and in the membrane, but SARS coronavirus two, the agent that causes COVID-19 does not encode that protein. Before 2002, before the first SARS epidemic, people studied coronavirus quite a lot. You'll be surprised to know that and we knew that coronavirus has caused several different kinds of diseases. Respiratory diseases caused by human coronaviruses OC43 and 229E, common cold viruses that's still circulating quite a lot, avian infectious bronchitis virus, bovine coronavirus. Coronaviruses can infect the central nervous system.
Susan Weiss:
This is typified by the neurotropic mouse hepatitis virus that causes encephalitis and demyelination, and has been studied as a model system for multiple sclerosis. Coronaviruses can to affect the liver, again the mouse virus. The GI virus is gastrointestinal viruses, the porcine transmissible gastroenteritis virus, avian infectious bronchitis virus, bovine coronavirus, mouse hepatitis virus, and feline coronavirus. Feline FIPV, another feline coronaviruses, causes peritonitis, a really severe disease, a fatal disease of cats. I just want to give a little bit of history because it seems like the general public might believe that coronaviruses were new, but they've really been around for a very long time.
Susan Weiss:
Well, I should say, from the '60s and '70s, the coronavirus field been studying the MHV model virus, as well as these animal viruses, for which there have been a lot of vaccine studies and the human cold coronaviruses. In the '60s and '70s, we knew about these human viruses that cause a common cold. OC43 can occasionally infect the lower respiratory tract and cause more severe illness, but until 2002, there was really not very much activity on studying these viruses and there were really no known other human coronaviruses, which is why in 2002, when SARS coronavirus emerged in China, it was pretty shocking to not only the world, but even the coronavirus scientists.
Susan Weiss:
After that period, people looked for coronaviruses because it was believed or pretty much known that SARS coronavirus originated in bats. People found many other coronaviruses in bat populations and this began the era of the pathogenic human coronaviruses, and as well as the bat viruses, scientists looked for other coronaviruses in humans and found two more, HKU1 and NL63. These viruses were intermediate pathogenicity. HKU1 causes pneumonia and NL63 causes bronchiolitis and croup. Again, things were pretty quiet in coronavirus world until 2012 when MERS coronavirus or Middle East Respiratory Virus emerged in the Middle East, causing a similar severe disease to SARS coronavirus.
Susan Weiss:
Again, things were quiet until just recently at the end of 2019, 2020, SARS coronavirus two emerged in China again, in Wuhan, China. Just to summarize SARS coronavirus here, MERS coronavirus here, and SARS coronavirus two, all cause severe respiratory diseases. This virus is clearly called SARS coronavirus two. It is incorrect to call the virus COVID-19. Coronavirus disease of 2019 or COVID-19 is the name of the disease caused by SARS coronavirus two. Okay. I think everyone's heard a little bit about zoonotic transmission of coronaviruses. As far as we know, all three of these epidemic viruses, both of the SARS and the MERS originated in bats.
Susan Weiss:
In the case of SARS, it's pretty clear that the precursor to SARS infected palm civets and then infected humans. This was we believe a very rare transmission and then once it got into humans, it very quickly spread among humans. It only lasted for about eight or nine months before it was pretty much eradicated in 2003. MERS coronavirus behaved a little bit differently. MERS is a reservoir in the camel. It's still in the camel and it's continuously shedding into humans. Still even in 2019, there are new infections of MERS coronavirus, mostly from camels to humans. It can also spread human to human, but not as readily as SARS does.
Susan Weiss:
Then the most recent virus, SARS coronavirus two probably had an intermediate host, but we really don't know what it is and it's been rumored to be this pangolin, this weird anteater like looking animal, but this is not at all proven. Then it was transmitted into humans and then as we all know, transmitted very quickly into many humans and became a worldwide epidemic. These two epidemics were quite different, SARS-CoV-2 and MERS-CoV, really stayed restricted to China and the Middle East, whereas this viruses as we all know traveled worldwide. Okay, this is a little bit more scientific here. I want to talk about the genomes or the genetic material of these viruses.
Susan Weiss:
All coronaviruses have very similar genome structure. They all have a very long replicates gene at the five prime end, and this gene encodes 16 non-structural proteins, and that's conserved among alpha and beta coronaviruses and all these lineages here. They all have spike E, M, and N. These are the structural proteins, genes encoded in the same order in the three prime end of the genome, but what makes them different from each other are these accessory protein genes that are these number genes here, 2a, 4, 5, et cetera. These are very different among the different lineages of viruses and these genes encode proteins that usually act to antagonize the host immune response.
Susan Weiss:
Just to show you where, so among alpha viruses are 229E and NL63. These are the less pathogenic viruses. Among the beta coronaviruses, the lineage A includes OC43, and HKU1, again, the less pathogenic viruses. The lineage B viruses includes SARS coronavirus, original SARS and lineage C, MERS coronavirus two. Very quickly after SARS-CoV-2 arose, it was sequence and shown to be very closely related to SARS, and that's why it's called SARS-CoV-2. There are some differences among these genomes that those may be interesting differences that make the virus behave differently from SARS, but we really don't know what they are as yet.
Susan Weiss:
Just really quickly, I'm going to show you the coronavirus life cycle. This is mouse hepatitis virus, but it's the same for all the viruses. Coronavirus is attached to the receptor via the spike protein shown here. The nucleocapsid is internalized into the cell, and it produces a replicase polymerase that then produces or transcribes seven subgenomic messenger RNAs as long as in addition to more genome RNA. These RNAs are translated into protein shown here. The membrane proteins are inserted into intracellular cytoplasmic membrane shown here, the nuclear capsule and RNA assemble, and this capsid buds into intracytoplasmic membranes here.
Susan Weiss:
Then the virus particles are in vesicles and extruded from the cell by a exocytic pathway, and that's true for really all coronaviruses. I want to talk just a little bit about a couple of steps in replication that might be good targets for antiviral therapies. Coronaviruses use two routes of entry into the cell. This route here, the virus attaches to its receptor, its endocyte host, and it goes through a series of vesicles and finally, it's released into the cell by a fusion of the viral and host membrane. This process involves cleavage of the spike glycoprotein by a protease called cathepsin, and this requires the low pH environments of this endosome.
Susan Weiss:
The other route requires virus attaches to a receptor again. It's cleaved by a different protease called TMPRSS2, and then this activates the spike to mediate cell virus fusion, and the nucleocapsid virus is put into the cytoplasm again to initiate an infection. This is important because which pathway is used depends on a combination of the protease sites in the viral spike protein and also the cell type in which proteases are accessible to the virus. Why is that important? Because when you think about designing antiviral therapies or antiviral compounds, they will be different depending on whether it uses the endosomal route or the direct plasma membrane route.
Susan Weiss:
For example, a lot of you have probably heard about chloroquine. There's a lot of scuttle about chloroquine. Chloroquine would only act on this pathway. It might prevent viral entry by this indiscernible pathway, but it wouldn't affect the plasma membrane entry. On the other hand, a TMPRSS2 inhibitor, for example, Camostat which has also been talked about would infect entry at this pathway. Since coronaviruses can use both pathways pretty readily, you might really need to use a combination of inhibitors to really shut down viral entry. I want to talk briefly about the transcription of coronavirus messenger RNA. This is a little bit complicated, but I think it's interesting.
Susan Weiss:
It shows the complexity of this virus. This is the genome RNA. It's got a cap five prime end and a polyadenylated three prime end. It also has these transcriptional regulatory sequences that denote the beginning of each messenger RNA that I'm going to talk about. The first thing that happens during infection is the genome is translated into an enzyme. A polymerase shown here. That polymerase hops on to the end of the genome and makes a negative strand copy of the RNA. The polymerase then hops on the end of the negative strand RNA making more genome RNA. This is replication.
Susan Weiss:
At the same time, the genome is transcribed into all these subgenomic RNAs by a really interesting process involving non-contiguous transcription, so that five prime sequences from this leader sequence for the negative strand is put onto each of these minus strand RNAs. Then each of these is copied back into messenger RNA. The blue RNAs are all the messenger RNAs that are translated, and the yellow RNAs are the negative strand templates for making all these RNAs. This process is pretty complicated and involves more than just the polymerase, some other enzymes and that's important for what I'm going to tell you in a minute. Here's the genome again.
Susan Weiss:
Each one of these RNAs is translated into viral protein shown in the brown, and this region is really interesting in that the replicase gene is translated into a polyprotein 1a, and another polyprotein 1a, 1b and that's moderated by a so called frame-shift mechanism. There's a pseudoknot structure in the RNA here that causes the ribosome to stutter at some frequency and switch translation frames of making proteins, so that we get PP1A. This protein is translated here and at about 5% of the time, there's a read through translation, so that we get this very long polyprotein. These proteins are then proteolyzed into 16 non-structural proteins.
Susan Weiss:
The reason that that's interesting or important is because among these proteins shown here, this again is ORF1a, 1b, are really good targets for antivirals. First, we have a 3C-like protease. This is a protease that cleaves all these sites producing all these proteins. Papain-like protease that cleaves at these first two sites, and an RNA dependent RNA polymerase. This mediates replication of the genome and transcription of mRNAs, and all of these are conserved proteins among all coronaviruses. You've probably heard of remdesivir, which is this compound or inhibitor targets the RDRP. There's also a couple of protease inhibitors that have been used to target this protease here.
Susan Weiss:
These are drugs that are already being tested for antivirals against coronavirus, but in addition to these three proteins, there are more proteins shown in the next slide encoded in ORF1a, 1b that have other activities. Again, they're conserved proteins, they're enzymes, and they're all possible targets for antiviral therapies. I won't go through them all, but they're important for both. They're promoting synthesis and stability of viral RNAs, the capping of five prime ends, and also protection from host cell sensors, and several of these are host interferon antagonists. Just to show you one example, this is structures of nsp13, which is the viral of helicase from SARS, from MERS and from the murine virus.
Susan Weiss:
We can see that this one inhibitor fits into the same structure of all of these three. At the same time, if we look here at viral production as a function of treatment with inhibitors, this particular compound inhibits all three viruses. This is the kind of paradigm for what we want in an inhibitor that might work on many or all coronaviruses and just mentioned one more thing, oops, vaccine development. There's lots of vaccine development going on now by many different mechanisms using attenuated virus, killed virus, the spike protein or just the region that recognizes the host cell receptor. There are RNA-based vaccines and DNA-based vaccines, so I'm going to stop here and I just want to acknowledge the people that work in my lab that are working very hard on the virus as we speak.
Susan Weiss:
Thank you I will stop here.
Joel Reich:
Great. Thank you, and Ed will be setting up his slides and we move from the research to more of the clinical realm, but obviously, a lot of the topics that Susan mentioned directly relate to therapies and vaccines that are in development. Ed, you're all set. You share your screen?
Ed Fein:
Yup, here we go. Okay. Well, thank you Susan. That's certainly a tough act to follow. I'm a clinician, so I'm working with patients every day. Here's just a little disclaimer because I have an employer, and we're not really supposed to talk about specifics. My opinions are mine, not my employers, and I'm speaking in aggregate. When I talk about things that happen at the hospitals, don't take it as something specifically happening at the hospital that I'm at. It's an aggregate from talking to people, and I have no conflicts of interest here. Just two seconds of background about myself, I graduated Brandeis in '85, Mount Sinai back in '89.
Ed Fein:
I did a fellowship in pulmonary and critical care, finished that back in 1995, and been practicing for 25 years in New Jersey. I was in private practice. I've done all kinds of things, so leadership positions and actually now, I'm trying to finish up an MBA in medical quality. When all this started, I was doing office work. I had maybe retired is a strong word, but I really hadn't been doing much ICU work so clearly there's a need for ICU doctors. I've been called up and I've been working in the ICUs for the last couple weeks. Just to mention what's different about COVID from other diseases, this is probably the only technical slide I have, if you want to call it that.
Ed Fein:
It's called R naught and it's a measure of how transmissible disease might be. If it's less than one, meaning everybody infects less than one person, the disease goes away quickly. For the coronavirus that we're dealing with now, it's at least two to three and maybe that could be an under estimate of how many people get infected per infected person, and that's why we keep talking about how each person can infect lots and lots of people. The flu is not that infectious. It's about one, maybe one and a half from what I've looked up, and that's why we really need to start all this testing and tracking of infectious people. A lot of changes to healthcare right now.
Ed Fein:
I saw 27% of you guys list yourself as physicians, but I know there's lots of different kinds of practices out there. I don't even know if people don't have sick family members or acquaintances that there's no elective or urgent procedures going on in New York, New Jersey and most of the country right now. If you need a routine procedure, it's not happening. I diagnosed somebody with a lung mass and they need a biopsy because they have cancer, probably have cancer, it's not happening. All these things are being delayed. I have a friend who was just diagnosed with a breast mass and typically that patient or she would... It's not patient, friend, she would have a lumpectomy first, changing the paradigms and she has to go on tamoxifen first which is a form of oral chemo.
Ed Fein:
Telehealth, which was a nice buzzword six weeks ago, but almost no insurance covered it. Now everybody's covering telehealth, so it's a real paradigm change. My patients are all getting used to getting us in touch with them on their iPhones. Even from a government perspective, there used to be a lot of rules. Most of us have heard of HIPAA. You have to sign that form when you get to the doctor and there's been a lot of... What you would call it? A lot of relaxation in those rules. I can use my iPhone to talk to somebody on FaceTime, whereas before that was not allowed, so lots of changes. The hospitals are very bizarre places right now.
Ed Fein:
The hospitals, there's no visitors allowed at all. When you walk through the hallways, it's very empty. Patients are all alone. There's no family members with them. There's no family at the bedside, and the only ones who are allowed to have somebody at the bedside is maternity. I think even in New York at first they said no, and then they gave in on that. The other question that most of us have is the hospitals are filled with COVID patients, and where are all the other patients? People with MIs are staying home, people with strokes are staying home. Few of the patients that we've seen are presenting with late disease. People are getting really sick at home before they're willing to go to the hospital, so that's not a good thing.
Ed Fein:
There's a lot of changes to healthcare right now. A few things that I don't see covered in the news, so I'll mention those. Ventilators, almost talking about that. Not as much now I think because we have done a good job of lessening the number of patients that are coming into the hospital. I think people here a lot of the ventilators are good because patients need them, and then I've seen a lot of reports in the late press about lung damage from treatment and proning, which is putting people on their stomachs which it's not a new concept, but I guess I'll also say this. The ICU is a very different place right now. I've never been in a situation where everybody in the ICU has the same disease.
Ed Fein:
It's very different. I don't know I've seen some reports of this on the news, but the nurses have been very clever and the facility's management at the hospital has been very clever. They moved all the pumps outside the rooms, so the nurses don't have to go into the rooms as often, so that's a very big change. The hallways are filled with pumps. The ventilators, I don't want to say they're causing damage, but it's a side effect because we blow air into the lungs of course. There are certain techniques to reduce lung damage, but sometimes it comes along. Life support, they use a lot of these words interchangeably and medically induced coma.
Ed Fein:
Medically induced coma just means that we've had to sedate somebody. The tube in the throat for when you're in the ICU can be uncomfortable. Some patients tolerate it well. You can walk in a room and somebody's watching TV and flipping the channels, and some people are very uncomfortable with the tube. Also, there are some modes of breathing that are difficult for people to breathe because they're not normal breathing patterns. Seeing a lot of patients with kidney failure with this disease. There's a lot of dialysis going on. Pneumonia, of course, is what's really bringing most people to the hospital. It's really a bilateral process, both lungs are involved.
Ed Fein:
Their oxygen levels get very low, something that's coming out more and more now as these patients get a coagulopathy, which means their blood is either too thick or too thin to use a lay term, and they're clotting. We don't really know how much or when to use blood thinners, but we're starting to get more experience with that. A lot of patients have cardiac issues. Their hearts aren't pumping well. There's some CNS, central nervous system issues or maybe even seen a case of Guillain–Barre, which is a rare disease where patients can't move. The other scarce resources are not just the ventilator. We see a lot of the dialysis machines.
Ed Fein:
We have to make decisions every day who needs dialysis more than somebody else. Some of the typical medications we use are getting short, so we have to make compromises about which medicines to use. I haven't seen anybody not get something they need, but we may be using things that we used 10 years ago and not five years ago. Not always a great difference in that and something that we use as a rescue is ECMO, which is extracorporeal membrane oxygenation, which is what you use when somebody is in a heart bypass having surgery.
Ed Fein:
We use that now to give people oxygen whose lungs don't work at all, and that's a very scarce resource because it takes a lot of skilled labor and a lot of skilled people to get that done and most hospitals maybe have two or three and that's also in a very specialized center. The experimental therapies that you hear about, Susan mentioned the Plaquenil, the azithromycin, remdesivir. To me, the problem is if something has no benefit, then it only has risk and when you combine Plaquenil and azithromycin, you can have problems. It's very, very difficult for us to tell clinically who's responding to these medicines. The patients are getting Plaquenil in the hospital, that's the chloroquine, hydroxychloroquine derivatives.
Ed Fein:
We are using it because they are fairly low risk, but in a disease where thankfully most people get better, it's hard to know if it's working. We are seeing that in the azithromycin. Right now in the hospital where a lot of the patients are having secondary infections and secondary complications, we're beyond the use of these therapies right now. They wouldn't help at all, and so there's the off label use, which means using the drugs like the Plaquenil and azithromycin which are available, I can prescribe them anytime I want. Then there's compassionate release versus a trial. Compassionate release sounds great, but it means we don't get good data.
Ed Fein:
You don't really want to do that, unless you're forced to and trials are really the best way to go. PPE, the personal protective equipment, we hear a lot about in the news about the masks. Just a few weeks ago, it was sitting around the hallways in a box, you could grab one whenever you wanted it, and we really didn't have that much fear of getting sick. I mean at least in my mind, the real point of the protective equipment was so that I didn't spread infection from patient to patient. I really wasn't scared about getting anything myself. Right now if you need some, you need the gear, you have to find the charge nurse. I mean, nobody's testing me how many days have I used my mask for, but we are returning the masks for cleaning.
Ed Fein:
We wear the N95 mask and then over that we put a surgical mask and the outside mask we change often, but the N95 we leave on between patients. Some hospitals have a buddy system to make sure you're donning and doffing your gown correctly and you're not touching things that you shouldn't. It's really an unprecedented risk. I trained in the HIV era back in the late '80s and the '90s. I mean, there were people back then who were afraid of catching HIV, but you had to have a needle stick and even if you had a needle stick, I think it was 0.1% or 0.01% risk of catching it from a needle stick. It's a very different concept.
Ed Fein:
Now I can name five, six, seven healthcare professionals that I know who have caught COVID and it's unclear where they got it. Some of them clearly in the hospitals, some not. Just a couple of comments about personal care. Most doctors do telehealth, so feel free to call your doctor and make an appointment. I think the telehealth has worked out really well even for my older patients. They've been very receptive to it and the main symptoms that we're seeing is that a dry cough, which is quite helpful, because right now the allergies are starting to get bad. When people have productive coughs, a lot less concern. Fever, myalgias, and rashes and testing is a big deal.
Ed Fein:
I would love to test everybody. We get calls all the time. We call them the worried well, they want to be tested. They know somebody who knows somebody who know somebody who had the disease and they're worried about it, but the only people I'm really... I don't want to say allowed because that's a tough word, but really discouraged testing people unless we think they really have the disease or you're getting admitted. If you go to the hospital and you're not sick enough to get admitted, they won't do a test. They're just going to send you home and say, "You might have it, go home. Call us if you get sick."
Ed Fein:
Even if there's a high suspicion in the hospital because they don't want to track down the results, so they just tell you, "You probably have it because you probably do." Masking is important, there's been a lot of stuff in the news about that. When should you go to the emergency room? The rules are the same as you might use on any other given day. If you're short of breath, you have underlying conditions, you're ill, I would say you should go and I wouldn't avoid the emergency room because of fear of catching something. I think you're more likely to cause yourself more trouble if you do that.
Ed Fein:
The most common reasons we're admitting people to the hospital is because they have a low oxygen level, and the low oxygen level means you need oxygen and you're high risk of having a complication, so that's really the most important thing. A positive thing I can tell you is most people don't get that ill. I've had patients or I've heard of people who their 80-year-old grandmother tested positive at a nursing home and never got sick and then unfortunately, we have nursing homes where it's really devastating, where 40 people have died in a nursing home. Most people don't get that ill, but the real risk and why we have to do the social distancing is because we have the potential to infect others and we don't want to do that, so that's what I got.
Joel Reich:
Great. Well, thank you Ed and thank you Susan for great presentations. We still have over 100 people on the call, which is great, and we've gotten a whole lot of questions. Some of them you may not hear your question because I may need to combine it with others. I'll do my best to read down the list and do that. Going into the first question, it's for both of you actually and it may be a hard one to answer but, "Is the current pandemic surprising to you or do you expect something like this to happen at some point with your clinical and your research backgrounds?" I'll throw that out to both of you.
Ed Fein:
You go first Susan. You're on mute.
Susan Weiss:
Right.
Joel Reich:
There you go.
Susan Weiss:
Unmute.
Joel Reich:
Yeah.
Ed Fein:
Good.
Joel Reich:
No, I think you muted by accident again. Hit it one more again.
Susan Weiss:
Okay, yeah.
Joel Reich:
Here you go.
Susan Weiss:
Okay. With the perspective of having gone through this SARS and MERS, we were quite shocked at the SARS epidemic and the MERS epidemic, but we really shouldn't be that shocked. No, I wasn't shocked. It was more like why didn't it happen before, but the extent of it is shocking because neither the other coronavirus epidemics were quite like this, but there's so many viruses in bats that can be transmitted to humans that it's not really surprising.
Ed Fein:
I probably have the same thought that I'm not surprised that we've had a pandemic, but just the extent of it is really... You don't really think about these things and again, even the main thing that's different to me is I've never felt the risk to the healthcare workers. Even we had AIDS, we had tuberculosis, you have lots of diseases, the real risk to all of us is the problem that I don't think any of us expected.
Joel Reich:
Okay, thank you. I'm going to combine a couple of questions, but there are several around antibodies and immunity. One is straightforward and simple is, "Do you think any people have natural immunity to the coronavirus, either from exposure to other coronaviruses or whatever?
Susan Weiss:
I think the answer in a word is no because this virus is so different from any... I mean, I can imagine that maybe some of the people that survived the SARS epidemic might have antibodies that cross react with SARS-CoV-2, but none of the cold viruses, the intermediate, none of them are close enough related that I would expect there to be any pre-immunity or cross reacting immunity.
Ed Fein:
Yeah, I would agree and around the hospital, a lot of us will like to say, "Well, the best we can hope is that we had a mild case and we didn't know it," and none of us really know that, but that's what we all like to believe.
Joel Reich:
Okay. Two well related questions, both related by being about testing, "Any thoughts on antibody testing?" Then the other question which is not about anti. It's about testing for the virus, not necessarily by antibodies, but, "Wouldn't it be more beneficial to be testing asymptomatic people than those presenting the common symptoms who already presumed to have it?"
Susan Weiss:
Well, who would you test everybody? If there were enough tests, theoretically great to test everybody, but which tests would you use? Remember, when you're testing for the illness in the beginning, you're testing for the RNA, you're testing for the virus itself. When you're testing later, you're testing for the antibodies. You're looking for people who had been infected, and they're really very different tests. You have to define exactly who would you test and for what.
Joel Reich:
Yup.
Ed Fein:
Yeah, and testing is very difficult, especially three weeks ago, if I did a test, it took about 10 days or more to come back. It was totally unhelpful. The patient, I did a test, they'd either be in the hospital or be better by the time it came back. It was really of no use. Now the turnaround time, closer to two or three days and you hear in the news about this test that is back in 10, 15 minutes, but that test, they can only run one at a time so that's still only for an hour. For that test, it's got a lot of false negatives. If it comes back positive, it's good test but if it comes back negative, then we still have to run the other one that takes a couple days.
Ed Fein:
It's not great and even today, the Abbott test, they were having some confusion about the media that it was put in. If I run a test in a lab, I know how often it's false positive, how often it's false negative. I know it's a lot about the test here, and to do the test, it's not a pleasant test. You have to take a Q-tip and it goes way back in the back of your nose. It's not something that's pleasant and a lot of people don't do it right either, so it's not 100%. Healthy people would be great if we had a easy test, but it's just not.
Joel Reich:
Yup. Moving a bit...
Susan Weiss:
Can I make it tiny comment about that? The actual test, the PCR reaction itself should take a couple hours, and it can be done in a high throughput way, I mean when we do stuff in the lab. Whatever it takes, two or three days is all about administration, about transfer, about...
Ed Fein:
Volume too.
Susan Weiss:
It's just not about the actual test. It shouldn't have to be that slow.
Ed Fein:
Well, even the drive through sites, they can handle about 200 a day, and that's pretty amazing considering none of these existed two weeks ago, even with a lot of effort and a lot of gearing up because the test takes a long time to do. Even talking about the ones with people who are in their cars where you just come over and do the thing in the nose, it's just very time intensive.
Joel Reich:
Yup.
Susan Weiss:
Again, it's not about the actual test. It's about all these stuff that's out there...
Ed Fein:
No, no, I understand. Well, that's why I'm saying it takes 15 minutes to do the test or less, but there's a lot of other things and the volume.
Joel Reich:
Yeah. A bunch of questions around what the pattern is going to be from here, second wave, third wave in the summer, the fall, the winter in and around of any thoughts you might have about all the movement in some states, in some parts of the country to "reopen." Maybe I'll throw that one to Ed first, just in terms of your observations from the clinical world, any thoughts on those topics?
Ed Fein:
I think the best thing I can answer is that I think what we've done in New York and New Jersey is working. I mean, the volume of admissions and people going to the ICU over the last week has dropped off dramatically. If we go back to what we were doing three weeks ago, it would be horrible and right now, the ICUs are filled with patients who were sick and haven't been able to get out of the ICU. They're stocked. I mean some hospitals and again, not just mine, there are hospitals that have converted their cafeterias into wards for patients. You have people who are doing jobs that they haven't done before.
Ed Fein:
My office staff because I'm not in the office was told they're going to be called to the hospital to work in the cafeteria because you're on staff, you're working for the hospital, and they'll put you anywhere they need you. I must still get... I get a lot of emails from hospitals all over the country because they find you. They're looking for critical care doctors all over. Right now, we have doctors coming from other parts of the country to New York and New Jersey, but if those other parts of the country get too busy, it's really going to be a lot of problems. I think it's safer to wait.
Joel Reich:
What about reinfection? Somebody has asked the question about the stories coming out of South Korea. They're claiming that 120 people have definitely recovered and gotten it again. Do you think that's more a function of testing false positives and negatives?
Ed Fein:
I don't even know if it's a false positive because I think Susan will tell you too. It depends what kind of test you do. If the RNA is still in the body and you're doing a PCR, it's just very sensitive. It's going to pick it up again, and we don't know how long it takes to clear that. It's unclear to me if they're reinfected or just leftovers.
Susan Weiss:
I mean, you have to be really careful about when you talk about the PCR test because like I said, it's RNA, and it's really sensitive. A colleague from China was telling me that you needed to have like maybe 1000 genome equivalents to be able to actually culture virus out of something, so there's like remnants of RNA and junk. I agree with that, that that may not really mean that there was a reinfection. Are they actually sick twice or they're just positive twice?
Ed Fein:
In the hospital in order to transfer out, they do two negative tests, so that's taking for most people seven to 10 days. If I want to clear somebody to go back to work, it's three days of no symptoms, no fever. That's when you can go back to work.
Susan Weiss:
What's the limitation of the test? Does it detect one genome or 10 genomes? I mean what's the negative sensitivity?
Ed Fein:
Yeah, and you don't even know which test you're getting. Is it going out to Quest and they do one test? Is it going to the research lab that's doing another test?
Susan Weiss:
It's all relative PCR. It's all relative to something. Yeah.
Joel Reich:
Yeah. What about children? I've not seen any clear explanation about why children seem to be getting... Fortunately getting infected less often and getting critically ill less often. Is there anything out there? We will ask Ed first. Anything out there that you've come across that explains that?
Ed Fein:
I really haven't seen much. What I will say is, from what I'm seeing in terms of age, first we heard if you were under 80, you were pretty safe. If you were over 60, you were possibly going to get sick and if you were under 50 or 30, no problems at all, but that's not really what I'm seeing. The 80-year-old plus that are in nursing homes, they're 80 and they're sick, so they're getting devastated. The patients I have in the ICU right now, they're really 45 to 65. That population if we believe what we were told six weeks ago, shouldn't be there, but they do have a lot of comorbidities. I wouldn't say they were sick, but they were people who had other medical problems and I guess children don't. I mean, that's all I can really say.
Susan Weiss:
I thought...
Joel Reich:
Yeah and then... Oh, go ahead.
Susan Weiss:
It's okay. I thought you could separate the age factors from the comorbidities that there was actually an age factor independent of comorbidities. Is that true do you think?
Ed Fein:
It's variable. There's one doctor I know who's a marathon runner, and she caught it. She's been able to stay out of the hospital, but again anecdotally, I heard stories, her oxygen level got low, and she tolerated it, and she did okay at home. If she wasn't a marathon runner and maybe was a little older, she's probably in her 40s, would she had done worse? It's hard to know. Most people get better. We're seeing a small percentage of the sick people in the hospital, but if so many people get sick, and I think there are many, many more people out who have this than show up in our emergency rooms that's related.
Joel Reich:
Yeah, and one of the other questions I was going to jump to now which I think you've answered related to testing and numbers, what percent of people actually have it. All that buzz about the study out in California a couple of days ago says it's probably 4% to 6%, but nobody really knows. Is there anything else that either of you have come across that would speak to that?
Ed Fein:
From what I'm told and again, this is a clinician story, when they're testing the OB patients when they come in and between 15% to 30% of the OB patients who are just coming in are positive.
Joel Reich:
Wow.
Susan Weiss:
Wow.
Joel Reich:
That's pretty amazing.
Ed Fein:
Take that as a story though.
Joel Reich:
Yeah. Now just a few questions, and I'm going to keep going now. We have quite a number of questions. We won't get to all of them. I'm trying to combine them. Questions around vaccine. We all hear vaccines take anywhere up to four years, five years, but now I think there's something like 60 different vaccine efforts underway across the world. Any thoughts on how fast it can be done, safely tested and rolled out?
Susan Weiss:
I trust Anthony Fauci's opinion. I think it would be realistic at least a year.
Ed Fein:
I would say at least a year, and then you have to find out if it works.
Susan Weiss:
Yeah.
Joel Reich:
Yeah, yeah. Exactly. One of the other question which I'm trying to refine was, "Well, how do we live between now and then? Do we stay on a lockdown? Do we stay masked? What do we do if it's going to take that long to get that many people in a population to immunity one way or the other?"
Susan Weiss:
Well, if universal testing would happen and we could figure out who's infected and who their contacts are, it would give us some information. People that knew they were positive could be or people that were actually infected could sequester, and then other people could be safe. I mean, that's the only thing I can think of. Other than that, I'm afraid to go out.
Joel Reich:
Yeah, I think a lot of us are there. The other question is one around, "Why the death rates so low in Japan, even though they didn't shut down till pretty late I know and by believing Sweden, they have not shut down and they seem to be doing okay." Another question related was, "Are there super-shedders or people that tend to spread the virus to a lot more people? Is that lifestyle or physiology?" Any any thoughts on those topics?
Ed Fein:
I think a lot of it has to do with if you subtract out in New York and New Jersey, probably the rest of the United States might look similar to Sweden. I don't know what the numbers are, but we forget, the population density in New York is probably similar to Wuhan than a lot of other places. You go other places in the world, the train system's not there. You're not on top of each other in elevators. How many people got sick with JFK airport? We just don't know.
Joel Reich:
Yup.
Ed Fein:
All those things.
Susan Weiss:
One other thing to add during the SARS epidemic, the first SARS, there were actually so called super-spreaders and I don't think anyone understands why they were super-spreaders. I don't think that's been talked about with this epidemic. I don't know it is or it isn't, but I haven't heard the word super-spreader this time.
Joel Reich:
The other interesting comment from one of the attendees who is in a health system that does 25,000 deliveries a year. I assume that's not in one unit but said, "We've seen 15% asymptomatic delivering mothers in the past two weeks, very similar to what it has observed." Oh yeah, an interesting question and really this one's for Susan for sure down at the cell level and that is, "You had mentioned that low pH may prevent entry to the cell or prevent the virus from doing its thing. Is there anything that can be done to actually affect the pH at the cellular level?"
Susan Weiss:
It's backwards. It's the low pH of the endosome that allows this fusion of the virus membrane with the host membrane. There's enzyme called cathepsin that cleaves the spike protein that triggers that fusion, so you need the low pH atmosphere of the endosome and there are agents like chloroquine. One of chloroquine's activities is that it prevents that or raises the pH of the endosome. There are drugs that work on that endosome, but I don't think this virus only enters through that pathway because it's sensitive to drugs that would suggest it's going through the other pathway.
Joel Reich:
Okay, good. Now I may have messed up where the pH mattered, but thank you. That answers the question a little. I've reread it. Let's move all down here. We have a lot of questions. Yeah. I don't know if there's any more information than what we hear on television every day if we dare to watch, but about other waves of infection. I mean, my sense is it's not going to to go away. We may see some dips, especially if we reopen things in parts of the country, but I'm curious of your other thoughts on that.
Ed Fein:
Yeah, it's not gone. We're just starting to get used to hearing about it and the hospitals are quieting down, the admissions are getting less. I'll also mention it's nice in the hospitals. They play music when somebody leaves the hospital, which never happened before. They bring all the staff to the exit to clap somebody out. There are some positive stories and you're not hearing the overhead codes as often. I think we've done a good job of flattening the curve. Unless we find out that lots and lots of people have had mild cases and are immune, nothing's really changed.
Susan Weiss:
I think everyone asks is it going to go away in the summer, and I think we don't know and that we'll find out. Maybe it really will go down in June or July and come back people. Most people think it'll come back.
Joel Reich:
Okay, here's one definitely for Susan. "I know that spike protein expressed in insect cells has been characterized. I'm interested to know if you know of any group that is characterized glycosylated spike protein, and what if any differences are found regarding binding of neutralizing monoclonal antibodies?" Now, if that's a quick answer, great. If not, maybe we can get back to the person afterwards.
Susan Weiss:
That's an I-don't-know answer that I don't know that any... but the insect cells glycoprotein would be glycosylated. I don't know the answer to that. I don't know that anybody knows that. That's a pretty sophisticated ask at this point.
Joel Reich:
Okay, well then they get an award for the most sophisticated question. Sorry, we can't answer it. Let's see. Yeah. Well, I think we touched on this, but maybe just, we're getting close to wrapping up. "Since the SARS and the COVID-19 virus have a lot of similarities, what's the major difference in terms of why vaccine or treatment here is so challenging?" I mean you can just summarize what you went through before.
Susan Weiss:
What makes it more challenging than what? Than...
Joel Reich:
Then I'd say for SARS or...
Susan Weiss:
Well, there's no vaccine for SARS or MERS so it's not more challenging. It's just that those viruses went away. I don't think it's inherently more challenging. I think this is worse, but the actual virology and vaccinology, people spent a lot of money on SARS and MERS vaccines, but they never came to fruition really. I don't know that it's going to be different, but this time, there's much more motivation to get it done.
Joel Reich:
Okay. Let's see, just as we roll into the last few minutes here. We still have almost 100 people, so we'll keep going for a few minutes-
Susan Weiss:
I don't know...
Joel Reich:
... if that's okay.
Susan Weiss:
Ninety-three. Ninety-three it says yes on mine.
Joel Reich:
Ninety-three, okay. Yeah so prognosis, we keep seeing all the good stuff that I just mentioned on television with people leaving the hospital. Are people leaving with a lot of known complications or are the people that do fairly well going home with their heart and their lungs and their kidneys working? I mean what do we expect after all this?
Ed Fein:
I think most people recover without a problem. but it's just such a large number of people getting sick, that there are lots of people who get very sick. You know what I mean? For most people, you'll do okay, but it's really... The ones I see, it's difficult. They're very sick, they need oxygen, they are on dialysis now. Even from the hospital, most people go home after a couple days or three days, and that's why it's different than a lot of other diseases and I think that's what makes unnerves a lot of us in the medical community. Normally, you see somebody come in. You say, "Oh they have this disease." I have a pretty good idea from experience who's going to do well who going to do well and who not.
Ed Fein:
With this disease, it's really hard to gauge what's going to happen next, so that's why we have to be so careful.
Joel Reich:
Okay and just a quick clarification, and then we'll maybe do one or two more quick questions, but 15% to 30% of OB are actively positive. Is that would Ed meant to say? I think you're saying they were not clinically sick, but they tested positive.
Ed Fein:
They're not sick, right, which is the same thing the person who's typed in, right? Most of the time, when you hear testing, that's somebody who's sick because we're not testing the well, but those are people being done as a study. If you come into the hospital, if you're positive, they don't want to put you with everybody else, and that's going to be a problem now once we open things back up to elective procedures. The talk is that in order to come to the hospital to have any kind of surgery or any kind of anything, you're going to need to be tested two days before you come in. We certainly don't have that capacity to do that. If somebody's sick now, I mean, it's hard now.
Ed Fein:
If I want to order a CAT scan on somebody, they don't really want to do it because that contaminates the hallway, the rooms, all the people involved. They really need to know who's sick and who's not. Just getting back to the question, in general, when you hear the numbers, that means they're sick, but for those OB patients, I think that's screening.
Joel Reich:
Last couple, really last two questions. One is about how is the morale in the hospital? We see such mixed stories on television, the horrible stress and then we see the celebration when people leave healthy. Where are people going to land as we hope the numbers keep coming down?
Ed Fein:
I haven't seen any bad morale at all. No. I think that's the news looking for people make a good story, the bad morale. I mean, I walk in the hospital, everybody's pleasant. It's a different kind of place though because there's no visitors in the hospital.
Joel Reich:
Yeah.
Ed Fein:
They make announcements thanking team members every morning. They do things that never really would have been done if your hospital is filled with hundreds and hundreds of people visiting, but the stories about the food are true. There's food all over the hospitals. Places are sending food in. The nurses are very well fed, but I haven't really heard anybody complain about anything.
Joel Reich:
Okay, so last question. I think a good one to end on. What do you say to people who believe that COVID-19 is "just another normal flu or the same as the flu?"
Susan Weiss:
It isn't.
Ed Fein:
It isn't.
Joel Reich:
Well, that's a good answer.
Ed Fein:
I mean like I said, when I showed up in the ICU, I've never seen everybody have the same disease.
Joel Reich:
Yeah.
Ed Fein:
Even if we have flu patients, there's two, three. It's just not 50 patients with the same disease in the ICU.
Joel Reich:
Okay. I think we're hitting the end of our time and actually, we've covered just about all of the 30 or 40 questions we've gotten. I want to thank everybody, including Dmitry for coming up with the idea, Nikki for organizing it, and obviously Susan and Ed for being our panelists. We would like to invite people to go to the alumni website which should be on the screen right now to look at upcoming events, and some are coming up real soon on. There's a lot of activity in the alumni association and with that, again thank you all for joining us and thank you panelists, and everybody stay safe out there.
Ed Fein:
Thanks everybody.
Susan Weiss:
Thank you.
Ed Fein:
Bye.
Speaker 5:
Thank you guys. You were great.
Susan Weiss:
Bye. Thanks.
Ed Fein:
Thanks.