Topic: "Third spike" in COVID-19 cases, plus the vaccine trials
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Dr. Edward Jones-Lopez - Assistant Professor & Infectious Diseases Specialist at Keck Medicine of USC & Investigator on the AstraZenea vaccine trial
Perry N. Halkitis, Ph.D., MS, MPH - Dean of the Rutgers School of Public Health
Dr. Stephen Spector - Professor, Pediatrics at UC San Diego & PI on the UCSD arm of the Moderna trial.
Robert Salata, MD - Infectious Disease Specialist and Chairman of the Department of Medicine at University Hospitals Cleveland Medical Center & Participating in the study of the Phase 2/3 global study by Pfizer Inc
Shobha Swaminathan MD - Associate Professor and the principal investigator for the Moderna trial at the Rutgers New Jersey Medical School.
Jeffrey A. Shaman, PhD, MS - Chief Science Officer at Coriell Life Sciences
When: Wednesday, October 29th, 3PM-4PM EDT
Where: Newswise Live Zoom Room
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Thom: Welcome to this Newswise live expert panel, today we’re talking about the Covid pandemic, the vaccine trials underway and other related topics. I want to go ahead and get started because we do have several panellists that we want to get to and I’d like to start by introducing Dr. Edward Jones Lopez, he’s assistant professor and infectious disease specialist at Keck Medicine and the University of Southern California. So Dr. Jones Lopez, you're working on the Astra Zeneca trail there at USC, last week we heard that the FDA has authorised resumption of that trial after it was determined that a participant who died of causes unrelated to the vaccine. Can you tell us about that process for resuming the trial and what people should know about how this has been a step to ensuring safety of the vaccine and what you think people should know about that process?
Dr. Jones: Sure, thank you very much for inviting me to participate in this distinguished panel. So, many people know the Astra Zeneca vaccine was paused about six weeks ago because of a side effect that occurred in the UK and that was an international pause and it was fortunately lifted last week I believe, Friday. Before that it had been lifted already in the UK, in Brazil and in South Africa which are the other four countries where this study is being conducted. So as of the next week probably there's going to be some changes to the consent form obviously and when those are approved as of next week probably, if not the week after that, enrollment into the trial will be resumed after the pause that occurred about six weeks ago.
Thom: Thank you Dr. Jones Lopez. I want to go next to Dr. Robert Salata. Dr. Salata is professor of Medicine and also epidemiology in international health at university hospitals and from Cleveland Medical Center Dr. Salata you are involved in the Pfizer trail, can you update us on the progress with enrollment in that trial, how many volunteers there are and what you're doing at University hospitals Cleveland medical center?
Dr. Salata: Thank you, and I want to appreciate the fact that several of my colleagues are on the panel as well. To add one thing to what Eddie Jones Lopez just said, that patient in the UK did not die, that occurred in the Johnson and Johnson Vaccine trial, but that side effect was called transverse myelitis but they determined, including very carefully here at our FDA and the NIH which is co-sponsoring that study, that this was not shone to be definitively related to the vaccine. The Pfizer study is different, it is a collaborative process between Pfizer – one of the largest pharmaceutical companies in the world, along with a German company called BioNTech and it is unlike the Astra Zeneca vaccine which has another virus called Adenovirus, the chimpanzee one, which is coupled to the corona virus genes and in this case it is something called messenger RNA which we all have, and its coupled to the spike protein that is the projection that you see in all pictures of the corona virus, and that is the target we think for developing an effective immune response in the end, as had been shown in earlier studies of SARS 1 in the early 2000 time period and also MERS the Middle Eastern Respiratory virus as well. And in preliminary studies, including the Astra Zeneca vaccine and this one, in monkey models it was antibodies that developed against that spike protein that were protective once vaccinated and then challenged with the infectious agent. So, we have been working on the Pfizer vaccine. We will be participating as well in Astra Zeneca, which for us is just opening, but we started to vaccinate folks in the late part of august and as of this week we have halted further enrollment at our site. We have enrolled 180 subjects to date, there are 120 places around the world that are participating, we’re the only one in North East Ohio and we have not seen any major safety signals in the Pfizer vaccine trials to date, and in the preliminary studies that were already published, there really is a very robust immune response to this particular vaccine and it has been shown both in terms of antibody response, which everybody has heard about and it was 5 to 10 times higher than we saw in natural infections and we’re looking to see about the longevity or the sustainability of that antibody response, but also we looked at Tcell responses, another form of immune response which we think will be important as well. That said, Pfizer is closing in on their intended recruitment target of 44,000, the only group that will be vaccinated into November will be a group of children between the age of 12 and 17 – and why was that done – well many advocates have pushed forward with that and when we get to the point of general distribution of vaccines in the United States and other countries, we want to know that its also safe and effective in children.
Thom: Thank you Dr. Salata, we haven’t heard yet about the younger adults being in any of these trials, that’s very interesting – thank you.
I want to go next to introduce Dr. Steven Spector from UCSD, Dr. Spector is a professor of pediatric at US San Diego and they are working on the Moderna Trial there at UCSD. Dr. Spector can you tell us a little bit about that, the Moderna trail has been reported to be coming along very quickly, what stage of things are you at in terms of administering the doses to all the volunteers and what can you tell us?
Dr. Spector: Well similar to the Pfizer vaccine, the Moderna vaccine is also a messenger RNA vaccine that’s in a lipid nano particle coat so that, that nano particle coat – one hopes the RNA to get into the muscle and two – serves as an adjuvant to induce the immune response. I think that this particular vaccine has gone through very similar studies as what you’ve heard in the pre-clinical aspect for the Pfizer study as well as Astra Zeneca, and the other vaccines that you’ll hear about.
Moderna’s trial has actually completed enrollment of the 30,000 participants and in fact last Friday it closed enrollment at approximately 30,400 study participants. I think importantly there was a major effort to expand the demographics of those individuals who participated in the study. In the end overall in the study there was about 67% whites, 20% Hispanic Latino, about 4.5% Asian and a little over 9% African American and black. I think the other thing that was very important about the study was that many sites such as our own tried to bring a demographic into the study that represents the community that we live in, and so for example here in San Diego where there's a lot larger Hispanic population of about 34% we were able to enroll 38% of Hispanic Latino into the study, about 3.5% African American or black – we have about a 4.5% in San Diego and I think importantly we actually enrolled less than 50% of our population in whites. So, its representative of our community and hopefully when this vaccine or any other vaccine is licensed, we can say that this vaccine has efficacy and safety broadly in people regardless of their ethnic or demographic backgrounds.
Thom: Thank you Dr. Spector, I want to introduce next Dr. Shobha Swaminathan, she’s an associate professor at Rutgers New Jersey Medical School and she’s the principal investigator for the Moderna Trial at that site, so similar to Dr. Spector you're working on the same vaccine trial, we talked about how that’s gotten to the full enrollment. Tell us a little bit about how that’s going at Rutgers and especially the importance of those under represented racial and ethnic minorities in your region.
Dr. Shobha: Thanks, so much Thom, as Dr. Spector just mentioned, the Moderna vaccine trial has completed enrollment, at Rutgers New Jersey Medical School we didn’t start enrollment as soon as many of the other sites, that being said we enrolled 57 participants at New Jersey Medical School. The reason we took our time is as Dr. Spector mentioned, representation of populations most vulnerable to this pandemic is critical to A) ensure that the vaccine once approved is actually proven to be safe and effective in those populations, but that also requires a lot of community engagement activities to get the communities trust and buy in. so we’ve had to engage our community multiple different sessions to increase awareness about these files to emphasize the safety measures that are in place, because at the end – once these vaccines are approved we want to make sure that there is public trust in these vaccines, because nothing will be effective if the people don’t take it. So, at our site, of the participants enrolled 70% were of different minorities including black and Hispanic and about 25% - in fact less than 25% were white because the second half of the enrollment Moderna made a big push to ensure that the clinical trial population was at least as representative as possible of the general US population so that the results would be applicable to the entire country.
Thom: Thank you Dr. Swaminathan, next I want to introduce Dr. Perry Halkitis, he’s dean of the Rutgers School of Public Health – Dr. Halkitis we’ve heard from all of these great doctors participating in these vaccine trials. As a public health expert let’s talk a little bit about where we are with the pandemic. We’re seeing record number of cases. Some areas of the country reaching ICU capacity, there's a lot of concern about this going in the wrong direction. What do you feel is driving these numbers and what needs to be done?
Dr. Halkitis: Thank you for that question Thom and thank you for the opportunity to be here and to share some ideas with my colleagues. I appreciate all of the efforts that are going on in developing the vaccines throughout the country and making sure that we have representation across the populations so the vaccines work. I want to add one caveat which hasn’t been said so far, these vaccines will only work if people trust them and if people actually take them. So, we have as much work to do on the behavioral aspect of the vaccine as we do on the biological aspect of the vaccine. So, having said that I think what we’ve seen over the course of the last several months, in fact throughout the course of this pandemic is a lack of behavioral maintenance. Public health folks know that human beings have a very difficult time maintaining their behaviors, whether it’s their seven days of antibiotics or five days of their gym or eating on a regular basis – good food, people have a hard time in maintaining behaviors and so the term Covid fatigue has been used, I don’t really like that term myself – I just think it’s just people following their behavioral patterns. That I think is ultimately driven from the work that we’ve done here at Rutgers School Public Health, in part by a lack of personal responsibility and altruism. I think it is very easy to think of one self as being immune to this disease without consideration to other human beings who might be more susceptible to the disease. The actual things that have perpetuated the virus and the spreading of the virus, has been for the most part informal social gatherings, or formal social gatherings for that matter. I thin that the restaurants and the gyms have been really careful about maintaining environments that are somewhat safe, but individual gatherings in peoples homes, in people backyards in peoples pools, have been the factor that has perpetuated this disease.
We also see the record highs in part because more and more younger people – 18 to 39 are getting infected with the disease, they are asymptomatic and they are potentially spreading the disease to older people who are then more susceptible. So as a result of all of this, what we’re seeing throughout Europe and in parts of the United States including here in my hometown of Newark is curfews and closures again and I think what we might expect over the course of the next month or so, certainly up to thanksgivings if not afterwards is surgical tailored pinpointed closing, I don’t think we’ll be able to shutdown the way we did before, I think there’ll be huge resistance to that, but we have to be methodical and thoughtful and close some things down just a little bit in order to contain the virus again until these great doctors give us the vaccine we actually need.
Thom: Thanks Dr. Halkitis, I next want to introduce Dr. Sean Diehl, an associate professor at the University of Vermont Larner College of Medicine, Dr. Diehl you recently published a study about antibodies in patients with Covid and your study found that the patients with more severe cases actually had correspondingly high levels of antibodies which seemed a little bit counter intuitive and I wonder if you can help us interpret this a little bit and understand what that means for that bodies ability to produce the antibodies against the Sars-Cov-2 virus?
Dr. Diehl: Thanks for that question and it’s a pleasure to be on the panel with all these other esteemed scientists and physicians helping us get through this. So, we had in the University of Vermont, we were able to leverage our team work across the pathology lab and our ICU clinicians to really try to understand how quickly the breadth of the antibody response that occurs during early Covid19 disease and we compared this to subjects that actually had contracted Covid-19 but had recovered in an outpatient setting all within roughly the same timeframe. So, within the inpatient group, those hospitalized folks, the higher antibody levels were found in the sickest patients, those requiring the longest ICU admission and those levels in general in the hospitalized folks were much higher than those found in patients who had recovered in an outpatient setting. So what we think this really means is that its reflective of an arms race between the virus and the immune system, so its really hard to actually measure a replicating virus in the upper airways in real time in a person, PCR doesn’t quite get to that, that’s just fragments of the virus, but the immune system does have mechanisms in place to be able to detect ongoing replicating virus and so we think that during this early infection state that more antibodies are being made as more virus grows, but then as the virus gets under control, these antibodies will remain, just like in the recovered patients and notably the kind of antibodies we measured are those that are called neutralizing antibodies that are focused against the spike protein that are subject of all of these vaccine candidates that are currently in progress, so we think that this boards really well in terms of the – some additional details on our study that we found equal responses in males and females, we found robust immune responses up to 93 years of age, that were similar to subjects that were infected six decades younger than them, so we really agree with the broad rolling out of a vaccine, trying to target lots of different ages and both biological sexes and the broad approach is the most effective one based on what we know from the live virus infection.
Thom: Thank you Dr. Diehl, I want to toss it to Dr. Spector who wanted to add something about that immune response that you studied.
Dr. Spector: One of the things I think that’s really important is that you not only make an antibody response but a cell mediated immune response and many of the people who end up being hospitalized in fact have an overshoot and what seems to be getting those peoples Covid-19 to the most difficulty is when you have this – what’s called cytokine storm in which in fact there are many cytokines that are being produced that lead to many of the complications associated with Covid-19.
Thom: Thank you Dr. Spector, I want to go ahead and introduce Dr. Jeffery Shaman, Dr. Shaman is the chief science officer at Coriell Life Sciences, Dr. Shaman as we’ve discussed some of the vaccines and some of the understandings of the immune response, I think this kind of leads nicely to treating the people who currently have it, while we hopefully wait to understand the efficacy of these vaccines as soon as possible, meanwhile there's people who need treatment right now. Your company has created a DNA based prescribing report using a genetic profile to make recommendations about what kinds of treatments can work best for certain patients and in a case study you guys had 2/3rd of participants found to potentially need some change to their treatment. What can you tell us about this kind of precision medicine approach and how that can also be deployed against Covid?
Dr. Shaman: Thank you for covering all of this and kudos to my colleagues on the line, and for covering things like precision medicine during this difficult time – Coriell Life Sciences uses a small sample of the patients spit to provide insight into which medications will be safe and which will be effective for that patient. So, pharmacogenomics is the medically relevant and clinically actionable science behind why some drugs work for some people and they just don’t work for others. We’ve all heard of people that take medications that don’t work for them. Many times, this is because of their genetics. Additionally, we have to deal with medications that cause side effects, everything from a belly ache to a headache to severe muscle pain and even cardiac issues. By preemptively testing a persons genetics we can really avoid that trial and error type prescribing that’s often the standard course of treatment, and the risks aren’t only genetic, Genedose live, the clinical decision support tool that we have provides information on every prescription over the counter, supplements on the market in the US and the drug drig interaction risks, the contraindications including those for Covid-19 disease, the FDA warnings, other medication specific risks are there as well. So, in that study you mentioned that we saw that 64% of patients should make changes to their treatment, we saw a majority of those acted upon by their prescribing physicians and this all equated to a reduction in healthcare costs, pharmacy spend, hospitalizations and even slip and falls and an increase in patient satisfaction rates amongst other metrics.
Thom: Thanks Dr. Shaman, for all the media who are on the call, please chat any questions you might have, we’ll be happy to call on you and go ahead and relay those questions or allow you to relay the question.
I want to go back to some of the doctors working on the trials and ask Dr. Jones Lopez and then each of the other doctors, what can you tell us about timeframes for some preliminary results or interim reporting? What can we expect from the Astra Zeneca trial in terms of when we might know more about the efficacy?
Dr. Jones Lopez: Sure, so obviously the time frame will be dependent on the enrollment period, as mentioned – two of the studies have either completed enrollment or are about to complete enrollment – the Pfizer and Moderna studies. The Astra Zeneca study is scheduled to enroll about 33,000 patients or volunteers in about two months, which is basically a very similar target to the other studies that I know of. The signal we really are looking at both safety signal and an efficacy signal, is going to be dependent on how quickly that enrollment period is completed. So, there is I think two views to this – there is an optimistic view and then there is more of a realistic view in terms of when will we expect a sufficiently robust signal, I'm talking mostly around [inaudible 24:12] and that will depend on a series of factors, the actual efficacy of the vaccine itself – we don’t really know how the relative efficacy of these different vaccines- we’re all shooting towards a minimum of 50% efficacy, but the vulnerability in that efficacy estimate is going to be significant potentially. The more effective vaccine compared to placebo – that’s the other important thing to consider here. All of the studies have a placebo arm, something like a natural infection arm where the rate of disease infection will occur spontaneously as people interact in their daily lives. So, one is the efficacy – the relative efficacy, the second is – according to where they live in the country, the different rates of how active the disease transmission is occurring, I think those are the two main drivers of efficacy. The other very important signal to keep our eyes on obviously is safety and the pausing of the Astra Zeneca and the Johnson and Johnson vaccines are obviously around very potentially concerning side effects that are related or not to the vaccine and that’s really about – that’s the reason why these pauses have occurred and in my mind it really just demonstrates – and this is a very important message to send to the public, it really demonstrates how the system is working as intended and we’re going through the standard safety assessments that includes the pre-clinical – of these large studies that are looking at both efficacy and safety. So, going back to the question, I think an optimistic view for the trials that have either completed enrollment or are about to complete enrollment is a signal that is going to appear that is going to make itself apparent in the next 3-6 months after completing enrollment and I would think that a more realistic view is maybe after that, meaning in the next 6 to 12 months I would say. So somewhere in those two you will probably see- you’ll start seeing a signal among the different vaccines that are out there.
Thom: Thank you Dr. Jones Lopez – we have a question from Sam Block from the counter- Sam I’d love to invite you to ask the question yourself if you want to enable your audio –
Sam: Sure, I'm a reporter to Food Focus publications, this question might be our of your wheelhouse but I'm wondering if you have any thoughts about the recent news reports of live corona virus being found on frozen food packaging and I guess the related question of surface transmission.
Thom: Thank you Sam, any of our panelists familiar with that report or have any thoughts to share – Dr. Diehl?
Dr. Diehl: I could take a crack at it, so yeah I heard about that report and in my lab we indeed studied this virus and other corona virus as well and the cold temperature is a good way to preserve virus and so if it’s really frozen – however a lot of things have to go exactly right for that – I think that non peer reviewed report of live corona virus, I think that was just put out by the Chinese CDC and then some very strong due diligence trying to find it wherever they can and in that case they were able to put it into a cell culture medium likely that is extremely conducive to growing virus, but in a real world situation I think a lot of things have to go exactly right for that to actually lead to a case of transmission in that case.
Thom: Dr. Salata I saw you gesture that you wanted to respond to this as well, please go ahead.
Dr. Salata: Yeah just briefly, over time and as more data has emerged, we feel that surface related virus which has been found is less of a risk for transmission than the respiratory droplets or even aerosolized, and there were some recent studies just put out about finding this in sewage, that is this virus – so I think it’s going to be inevitable that we’re going to find it in multiple places. The relevance, the clinical and epidemiologic evidence that really – that’s a major threat for transmission, has to been proven yet and that’s the same posture that the center for disease control has taken at this point.
Thom: Dr. Halkitis
Dr. Halkitis: I think my colleagues have provided very remarkable information here, we have to keep in mind though that this is so reminiscent to me of that first decade of AIDS- for those of us who lived through it, where every single day there was a new piece of information and I think what is challenging for so many of us doing public health work is these reports are coming out like one after another and people don’t know. So, I'm encouraging all of us, as much as possible, especially the press to be particularly skeptical when things come out and to present them in a manner that doesn’t create panic because that is partially what we’re seeing right now in response to this disease by the human beings in our world.
Thom: Thank you Dr. Halkitis. We have another question from Jody, she’s a nurse and also writes for Quoted and for Hero she asks if the Covid vaccines are expected to have similar effectiveness rates as our current flu vaccines? Who can help us understand the comparison between the Covid vaccine and the flu vaccines?
Dr. Shobha: Thanks Thom, I personally don’t like to compare the two vaccines, although they are quite comparable because they are two completely different viruses and follow completely different pathophysiology, but to put it simply, based on the information A] we don’t know the efficacy of the Covid vaccine, what will be – that’s what these clinical trails are trying to establish. And given the number of vaccines that are in development, its likely when they are approved they will be – some vaccines may be great in some populations and some in others and that’s why we want to make sure that all these vaccines are studied in different age groups among different racial ethnic backgrounds, to see, to look at the nuances in these various age groups.
Now there are big differences with the flu vaccine. The flu vaccine and the influenza virus itself, undergoes periodic changes in the viral antigens and depending on the degree of changes, the flu vaccine that’s developed every year, has to adapt and we’re always playing catch up with the flu, which is why every year with influenza the efficacy of the vaccine varies. In a good year it can be as high as 90%, in a bad year it could only be 60-70% effective, but that still doesn’t mean it’s not effective, because even if you get the flu after getting the flu shot, you typically will have a much milder illness. We hope that with the corona virus vaccine that the antibody responses are robust and potent and hopefully we’ll not require an annual shot, but we don’t know that. So these clinical trials will need to be followed to determine the type of the response and the durability of the response and lets not forget, flu has been around for over a century – right – Covid has been around for less than a year, so the information and a month in Covid life timeline has been like light years, so the information that’s provided today may be already outdated in a couple of a days, so I think we have to look at the evidence and see where the science takes us with respect to the potency and the durability of the vaccines.
Thom: Thank you Dr. Swaminathan, Dr. Spector you wanted to add something.
Dr. Spector: Yeah there are several points that I think are very important to understand. The first is that most of these vaccine studies are powered to 60% efficacy, so hopefully they’ll be better than that, but they’re powered to show us 60% efficacy. Keep in mind that to have herd immunity we’d like to see at least 70% if not higher than that, and if you look at now those adults within the US that say they are willing to take a Covid-19 vaccine study today, only 50% of people say that they are willing to take the vaccine. So the vaccine itself is not going to be something that will get us out of this pandemic, it is one tool that we will have that hopefully will decrease the circulation of Covid-19 and decrease the number of people who are becoming infected, decrease hospitalisations and decrease those who are dying, but that needs to be combined with all the other public health measures that we are doing right now, cause the vaccine is not going to be the answer. It’s going to be one of the things that’s going to help us get out of the pandemic.
Thom: We have a question from Samantha Black, she’s from Science Board, and she asked – in a recent publication researchers reported that antibody responses seemed to last up to 5 months in mild cases of Covid, how long do the various vaccine manufacturers expect to track the long-term antibodies and protection through these clinical trials? Dr. Salata –
Dr. Salata: So in the Pfizer study we’re following volunteers for up to 26 months to look at the durability of the antibody response, and with regard to their recent publication and that was addressed by Dr. Diehl to some extent – people who had lower symptomatic disease had higher levels of antibodies, and then in a separate observation, some of those lasted seven months but there are other observations were three months and they are waned. But immunologists suspect that if you are re-challenged with COVID-19, you may indeed have a rise in your antibody response that may be protected. We do know about reinfection and that's been recorded in various countries now and including in the United States. But given that 47 million people around the world have been infected, and there are only a handful of scientifically documented reinfection cases that still is few and far between at this point in time, and I think that's important to emphasize. A couple of other points, if I may return to the influenza situation – two points. One is last year and in the last several years, the efficacy rate has been more along the lines of 40 to 50%, at best, and that depends on the age group. It's much less so in the older folks. But there again I do agree that even if they develop breakthrough disease, despite being vaccinated, they have milder disease, are less often hospitalized and die less frequently. So it's still worthwhile. And especially giving the flu vaccine this season in the context of the so-called twindemic is very important to understand and get that message out. However, if there's any silver lining about influenza and other respiratory viral infections aside from coronavirus, if you look at the southern hemisphere where they have seasons opposite from ours, this particular season, there were very few cases and mild cases at that. For instance, in the entire country of Australia where they usually see about 70,000 cases annually, this was about 70. And then the entire country of South Africa, they saw one documented case. So all the public health measures that are being put into place, that have already been mentioned and emphasized, are probably very effective also against other respiratory viruses including influenza, another one in children, although it's starting to be seen more in adults and that's respiratory syncytial virus, and so on and so forth. And I agree that the vaccine alone will not be the sole answer here. It will add to the amount of antibody responses and T-cell responses in the general population. And hopefully we'll get to that level of herd immunity that was already mentioned, but it will take a while and we will not be able to move away from these strict public health measures in the interim.
Thom: Thank you, Dr. Salata. Dr. Diehl, what would you also add to the length of that antibody and immune system response?
Dr. Diehl: The original SARS virus from 2003, which was contained much more quickly because the clinical cases were very easy to identify but still it infected a fair number of people back then, those individuals have been re-bled this year and they are tested for neutralizing antibody 17 years later after they contracted the original SARS virus, which is as this audience will recall, is very, very related to the current SARS-CoV-2 virus that's currently circulating. And 17 years later after exposure to SARS 1, these individuals had still retained strong neutralizing antibody responses and antigen specific memory T-cell responses that are able to be detected all this time after an infection. That's a case of natural affection, so I can't speak exactly to what vaccine will do because there was no SARS 1 vaccine that was ever rolled out. However, just based on the viral characteristics being in the same antigenic family, we think this bodes well for long-term protection to COVID-19.
Thom: I want to ask Dr. Swaminathan to tell us about the upcoming goal for interim analysis of the Moderna trial. And I want to work in another question from Jody, who asked a question a little while ago, about whether or not the COVID virus mutating may have any impact on the vaccine?
Dr. Shobha: So, Thom, let me answer the first part of your question with respect to the interim analysis. So, as has been discussed, the Moderna vaccine is fully enrolled at just over 30,000 participants and the way the study has already designed the setup, was interim analysis are triggered when a set number of infections occur in the study population. And there's two interim analysis plan for Moderna and then one a final analysis, depending on what the data show at each of those time points. The first analysis is scheduled to occur when 53 cases of symptomatic COVID infections are diagnosed within the study population. So what I mean by that is persons who are enrolled in the trial would be to have symptoms consistent with COVID-19 that will trigger them getting tested for the virus, and they have to be confirmed to have the infection to actually account for a case. And when 53 such cases accumulate the study code which we think will happen sometime in November, and that's based on when the study completed enrolment and based on the increase in cases nationwide. And at that point, statisticians will look at the data and then look at the number of cases that occurred in the placebo versus those according in the vaccine and also look at the safety data. And at that time, the DSMB, the statisticians along with the FDA, will need to make additional decisions about what to do with those data because you still have – at that point is the vaccine efficacious enough and has met the threshold to really say okay, it meets threshold for emergency use authorization? And the FDA recently provided guidance and they have released a whole document on the types of things that companies, that any vaccine manufacturer would actually need to meet to be able to be eligible for EUA, for emergency use authorizations. We think that will happen in November, but the time will tell. So the timing has nothing to do with the election, it just happened to be the timing based on when the study completed enrolment to when the analysis was. And your second question, I am sorry?
Thom: Will mutations of the COVID virus potentially affect the vaccine?
Dr. Shobha: Currently we haven’t seen significant changes in the COVID-19 vaccine, so as you know, most of the vaccine candidates are currently targeting the spike protein, S protein that appears to be consistent in all the viral strains that have been studied. So, will that necessarily remain true over time? Time will tell. We currently haven't seen evidence to suggest that there will be significant changes to the strains of the virus that will negate the efficacy of the vaccine candidates – are being studied currently.
Thom: Just one clarification, I see a chat asking about those 53 cases. I take that to mean this is among the actual vaccine recipients as well as the placebo, right?
Dr. Shobha: It’s the entire study cohort because we don't know – we, as the study investigators and the study team, are blinded. So we don't know who actually gets the vaccine versus the placebo. So that's total.
Thom: And so among those 53, if approximately fewer than 20 of the ones who get COVID got the actual vaccine, that would be about the threshold that you are looking for?
Dr. Shobha: Yes, it's about 31 to 32 cases in the placebo to about 20 or so in the vaccine. That's the threshold. Now, it could be fewer in the number of infections in the vaccine in case the vaccine is more efficacious. It'll be more effective.
Thom: Thank you. Dr. Swaminathan. As we talk about understanding the vaccine, again the current issue being the rise in cases and as Dr. Spector put so well earlier that the vaccine really is just one tool of many and continuing with various other interventions is going to be necessary, I want to ask Dr. Halkitis about a study out of the University of Kansas recently that identified that counties in Kansas that implemented mask mandates had 50% fewer cases. Dr. Halkitis, is there any reason to doubt the effectiveness of mask wearing and what would you like the public to understand about this question?
Dr. Halkitis: Yes, so thanks for that question. So as a scientist, you are trained never to say 100% certain, but I will say 99.9% certain that masks are effective in a variety of different ways. The study out of Kansas parallels another set of data that have come out of Tennessee, that have shown that hospitalizations in counties that have mask wearing in this second wave that we are going through, are lower than in ones that do not require mask wearing. So, in the absence of a randomized control trial, these naturally occurring experiments in Kansas, in Tennessee, as Dr. Salata said in Chile and Australia as we saw with flu season, provides sufficient indication that masks are protective. So they protect the people who are vulnerable. However, I believe we will ultimately find that they are ultimately protective to the person who's wearing the mask also. And so masks are effective – that is a message that is consistent. The challenge we face of course in our country, is that the mask has become political. And when you make something that is scientific, political, it loses its efficacy, but there is no doubt, reporters – mask wearing is an effective way of mitigating the disease.
Thom: Thank you, Dr. Halkitis. Dr. Shaman, I'd love to ask you about the types of patients in terms of prevention or preparedness as the pandemic spreads. What types of patients should consider getting the screening and prescribing report that Coriell offers and what that could then give advantages to in terms of treatment if they do have the misfortune of contracting COVID?
Dr. Shaman: So the CDC and Johns Hopkins’ guidance is currently, they continue to state that there's no need to discontinue a patient's medication regimen just because of a COVID-19 diagnosis. But the importance of being on the right medication with high efficacy and no side effects is more important now than ever. But I think it's really true for medications used to treat both the symptoms of COVID, those used in the course of treating severe cases or hospitalizations, those used in clinical trials for treatment and even those that had started prior to diagnosis. So those include the antivirals, the antidepressants, pain management medications, anticoagulants and even the immunomodulators. So what we know is that there's a list of indication known to increase the severity of a COVID case. So having therapeutically well-controlled chronic diseases decrease these risks, and we want to mitigate the cardiovascular challenges that are also potential side-effects of some of the medications being used. So, fighting the virus concurrently with a patient's existing conditions is enough of a challenge. Our goal and it should be all of ours, is to improve medication management so we are not also fighting against treatment, side-effects and lack of efficacy. So, during the pandemic, the folks that will benefit the most from the COVID precision prescribing report are those suffering from these comorbidities, polypharmacy, uncontrolled or poorly controlled chronic illnesses, dealing with medication side effects. And I think I would add to that list, something we all need to think about is, those receiving treatment for anxiety and depression. But because these genetic tests help for the entire life of the patient, these genes don't change over time. Anyone can benefit from these precision prescribing reports.
Thom: Thank you, Dr. Shaman. I'd like to ask Dr. Salata about the Pfizer trial and what can you tell us about the timeframes for an interim analysis? And what are those expectations in that study?
Dr. Salata: So thanks for the question. In the Pfizer trial, we are ready, have sent all information along about the first 15,000 individuals that were in the study; with the next 15,000, probably by next week, in their hands. They also expect like in the Moderna situation that they'll have information to the FDA and the independent panels by early November. And remember that Pfizer and many of the other manufacturers of vaccines, were given federal money. Pfizer – 1.95 billion to deliver up to 100 million vaccines by the end of December. And that is dependent, that amount of reward is dependent upon that. So they are moving rapidly. But I would like to emphasize what I think is an appropriate phrase, everybody has heard about Operation Warp Speed. To me that has potential connotation that we are cutting corners and that's far from the case with all of these vaccine campaigns. But the Pfizer CEO recently said we should move at the speed of science. And I think that's a more appropriate term as to what this is all about. So they are going to deliver, and I think they will, up to 100 million vaccines. But given that Pfizer, Moderna and even the AstraZeneca vaccine requires two separate injections, that will only cover 50 million Americans. And with 325 to 330 million, assuming everyone will take the vaccine – we already spoke about that – we need much more. And I also, to end, would say we are going to need multiple vaccine platforms because of the sheer numbers and the distribution issues and everything else. So we welcome those studies with our colleagues that are doing the Moderna vaccine, the AstraZeneca vaccine, and when Johnson & Johnson is supposed to start up again this week, and we are going to need multiple options – bottom line.
Thom: Thank you, Dr. Salata. Dr. Jones-Lopez, dig into that a little bit further as Dr. Salata alluded to one vaccine might come out and then another might then come out that's more effective or there might be differences for certain populations, tell us a little bit about what that means and what the public should expect with that process? Dr. Jones-Lopez, are you frozen? No, there you are.
Dr. Jones-Lopez: Sure. Yes, I think I am having some internet trouble. I think I heard your question which is to discuss the potential application of certain vaccines having another vaccine, is it correct?
Thom: Yes, something coming out after an initial vaccine that might be more effective?
Dr. Jones-Lopez: Yes, I've been thinking about these issues for some time now and I think actually that this is probably going to be one of the most challenging elements in front of us in the next six months. It's going to be difficult to navigate exactly what to do for each vaccine candidate as efficacy signals start coming out. I am thinking of first six to eight vaccine platforms, from the time of enrolment to the time of closure of enrolment, it's going to be roughly around [? 51:56 – inaudible technical issues]. Pfizer, Moderna being the first ones that [? 52:06 – inaudible technical issues].
Thom: Unfortunately, Dr. Jones-Lopez, we are losing your audio. I am very sorry, Dr. Jones-Lopez, we are losing your audio and it was breaking up there. Let me toss this to Dr. Spector. Dr. Salata, I understand has a heart out in a couple of minutes, did you want to?
Dr. Salata: I just want to make one comment. Thank you, Thom.
Thom: Please go ahead, sure.
Dr. Salata: We are not going to have comparative studies between these vaccines, so they are going to be surrogate markers and also what was discussed by our colleague from Rutgers and others related to the antibody responses, the durability, but also those cases, true cases of COVID-19 and those that are vaccine versus placebo recipients, and the safety signal. So, one thing that will happen is I don't think we should be mixing the vaccines. That's inherent in your question – somebody starts with Pfizer, they should not move to Moderna and vice versa, because that's not the way they are studied right now. But I think over time we'll be able to look at the effectiveness of these vaccines and the primary endpoint in all the vaccine studies is the number of true COVID cases between the groups. And that's going to take a while longer to accumulate that data accordingly. So I think we are going to have to start with these so-called surrogate markers, the antibody markers and the T-cell responses. There'll be some data initially on the number of COVID cases between the groups, but it's not going to be such that that is the end of the story, as this continues on.
Thom: Thank you, Dr. Salata. And I understand that you do have a heart out in a couple of ideas, so if you have to go before, we wrap everything up, thank you so much for participating today.
Dr. Salata: Thank you for including me and to my esteemed colleagues, it's been terrific. Thank you.
Thom: Thank you. Dr. Spector, what can you add on that question about an initial vaccine and then further vaccines coming out, maybe more effective or different indications?
Dr. Spector: Well, I think that there is an important population that to date has been overlooked with the vaccine, and we have to keep that in mind. There are 74 million children in the US who have not been studied and it's only the Pfizer vaccine that has now started to go down to age 12. We know that although children seem to be less likely to get COVID-19, they still do get illnesses associated with the infection, and we also know that they can be excellent carriers of viruses. For any of you who have ever had preschool children or school children, you know that the vector for bringing the virus into the home is often the school-aged child. And so we need to be cognizant that these vaccines need to be studied in children who are less than 18 and it needs to go down to school-aged children as well. Now there's unlikely to be efficacy studies in children and so that identifying what are the correlates of protection from the vaccine studies that are going on, so that you can now look at the immunologic effect of these correlates and how they present themselves following the vaccine in children, will be absolutely critical to expanding it to populations that are likely to be some of the most important carriers to the home of the infection.
Thom: Dr. Diehl, you had something that you'd like to add on this question?
Dr. Diehl: Yes, about the outlook on the vaccines. I mean as we start to know a little bit more about how the virus actually behaves, we'll be able to design better and better vaccines as we go. All of the vaccines being talked about right now are version 1.0 vaccines. They are just one part of the virus and was informed by some studies on SARS and MERS and other coronaviruses. But as we learn how to tame the virus in the lab, we can start working towards really one shot long-term, years to decades long for protection that you get with live attenuated viral vaccines. So these are likely to be a really important stopgap measure right now because none of these technologies have ever been shown to stop a pandemic in its tracks. That's an important point. And so this is a really exciting time for vaccine development because these technologies get applied to every outbreak that happened. I was around for Zika a few years ago, and mRNA vaccines and the like were also tried. And that epidemic died out too quickly to really find out how long those immune responses last. But they formed a really good proof of concept for being able to respond to more outbreaks and then getting these new technologies through the approval pipeline is really good from a broader sense to fight not just COVID-19 but the next pandemic that can come, as the viruses have an infinitely more higher capacity to find ways to infect humans than we currently have in the toolbox. But this response to the pandemic is going to greatly help our preparedness going forward for a lot of different things.
Thom: Dr. Swaminathan?
Dr. Shobha: Thank you, Thom. So I just wanted to add – so while there are different vaccine candidates being studied, because of the investment by the NIH and the federal government, most of these clinical trials have a harmonized study design. So they have relatively overlapping, although with some nuances, inclusion exclusion criteria, they have harmonized and relatively standardized study endpoints and statistical measures, to really help us be able to compare even though the vaccine studies are directly not head to head, so it's not like we are comparing Moderna with Pfizer directly against one another. But the studies are being done sparingly enough that you should be able to look at the results and make that decision. Secondly, with respect to endpoints, different vaccines maybe better in different aspects and what I mean by that is, some vaccines may be much better at protecting severe coronavirus, associated with lung infections which typically cause a higher mortality and morbidity. It's also possible some viruses may be more effective in the upper respiratory tract and, therefore, have a higher impact on viral shedding and spread up infection. So they may be better used, as Dr. Spector put it, for children – having young kids, they maybe the best candidates for that. And with respect to timeline, it becomes a personal decision because you try to evaluate your own risk, because if you are a first responder, if you are a person with underlying health condition or a senior citizen, you might not have the luxury of waiting for a version 2.0 vaccine down the road. You may want to get one earlier because you are trying to weigh the benefit of the vaccine versus waiting for something else better. So it ends up becoming a little more nuanced once we have more information.
Thom: I want to go to Dr. Halkitis to bring us back to what needs to be done right now and what people need to understand right now as we hold up the hope for one of these vaccines working. And I'd like to ask you if you can remind us about the importance of understanding asymptomatic cases and the pre-symptomatic phase of infectiousness. I feel like this is the thing that gets lost and forgotten about by a lot of people. And I wonder if you could really put an opinion in that for us.
Dr. Halkitis: I'll put an opinion in that. I also want to just add on to my colleague Shobha’s comment, just briefly say that we ourselves also remember that again, we have lessons in the past. AIDS taught us lessons. People took medications that were not the best medications to begin with, as a way of surviving, and the people who were sickest, took them right away. And eventually we had classes of medications that are better. So, for the people who need to take the vaccine, they should take the vaccine like the first responders, like Shobha said. So, back to your question, I am sorry I just needed to add that. Some would say we test too much. I would say that's a fallacy. We test because 40 to 50% of people who are infected with this virus are asymptomatic and those asymptomatic people have the potential to spread the disease to those who are most vulnerable, who will become extremely sick and who will die. So, given the fact that there are 40 to 50% of people who are asymptomatic out there, it is critically important that we continue to test at extremely high rates. We continue to test, to target a test like we are doing at Rutgers – our football team is being tested, the other sports teams are being tested. When people come back to campus, they are going to be required to be tested. So, testing is extremely important. It is often forgotten that the person who you are interacting with, who looks perfectly fine, who feels perfectly fine, may in their body, in their vessel, contain a virus who will make the person that they are talking to incredibly sick and potentially die. So, keeping cautious, putting our masks on, testing – these are all strategies that are intended for the well-being of the whole society. And we have to keep doing it at these levels and we should not deter people from testing at all.
Thom: Thank you Dr. Halkitis. I want to ask Dr. Shaman, similarly with the kinds of precautions, somebody who might be in a high-risk population could really benefit from the type of screening that Coriell offers. How would somebody go about requesting that from their physician?
Dr. Shaman: So this is not a direct consumer test, you are absolutely right. This needs a prescription like other tests out there. And I would say, the best thing and the quickest is to reach out to the website, coriell.com to learn more to be able to order those tests from a physician.
Thom: Thank you, Dr. Shaman. I feel like we are just about out of time. I don't want to burden these very busy doctors any longer, so you can go back to your very important work. But I want to thank you all for joining and just a reminder to all the media who are on the call – we have a recording and we will have a transcript. If you've registered for today's event, you are going to get those things. We are going to email them to you first thing tomorrow morning. If you didn't register and you just popped in because you got a link in an invite with us or something, and you want to get that recording and transcript, shoot us an email at [email protected] and we will make sure to add you to that list to get that information. We will also make sure to provide the contact details for all of the PIOs so that if you want to follow up with any of the panellists today with further questions or requests for interview or any other information about what they are working on, you'll be able to contact those PIOs to request that information. With that I will say thank you very much to all of our panellists – Dr. Jones-Lopez, Dr. Halkitis, Dr. Shaman, Dr. Diehl, Dr. Spector and Dr. Swaminathan. Thank you all very much for participating today. Thank you to the media who joined our call and stay safe, stay healthy and good luck.