COVID-19: Where We Are in the Pandemic and What’s Next [Video + Transcript]

COVID-19: Where We Are in the Pandemic and What’s Next with Sanjay Mishra, PhD (Science Speaks Series)

(Transcript has been lightly edited for clarity and length)

Aaram A. Kumar: Hi, everyone, welcome to this episode of Science Speaks, an Interview series from Sciencera that discusses a variety of topics about science and life in the world of science. I’m your host, Aaram A. Kumar, and that today we have with us Dr. Sanjay Mishra. We will discuss with him about where we are in the COVID-19 pandemic and what’s next in the fight against SARS-CoV-2.

Dr. Mishra is a staff scientist at the Vanderbilt University Medical Center and a project coordinator of the COVID-19 and Cancer Consortium, an international group of over one hundred and twenty five cancer centers and other organizations who collect and study data about cancer patients with patients who have been diagnosed with COVID-19 in his work and writings and COVID-19 that have been featured by top scientific journals like The Lancet and Science, and by news outlets like Reuters, The Conversation, Fox News and more. So welcome, Sanjay!

Thank you so much for taking the time to chat with us. We really appreciate it. Before we dive into the topic, I was wondering, could you give us a quick overview of the work done by the COVID-19 and Cancer Consortium.

Sanjay Mishra, PhD: Thank you and I really appreciate your time, your chance to talk to you. So the consortium, and I would use the CCC-19, which is what we like, CCC-19 is a consortium that I always joke that it’s the only good thing that has come out of the Twitter in, say, 2020 20, we were formed by a quick tweet by a fellow and asking for a simple question that the cancer patients are especially vulnerable to the COVID-19. And from that question, the consortium was quickly put together and we are collecting these identified, manually curated data on adult patients with current or staphylococcal, invasive, solid or hematological maintenances who have been diagnosed with, COVID-19, with or without a laboratory confirmation of the SARS-CoV-2 infection.

This is one of those examples where the entire data collection has been voluntarily. We do not compensate anyone. And despite of that, one hundred and twenty five centers as of this date are participating. Like I said, across North and South America, we have partnered with European agencies, with the European Nodal Agency for the Cancer Scientists. And this is one of the biggest data collection of this type anywhere done.

Aaram A. Kumar: Yeah, that’s just incredible and to think that all that started with a tweet. Just amazing, especially the sites and this being completely voluntary. So, I wanted to ask you what has it been like to be coordinating one hundred and twenty five centers and collaborating with them. So what has it been like to work in and coordinate such a massive collaborative effort?

Sanjay Mishra, PhD: Before I go into it, before I dwell more into it, the one thing I would say is that this has been highly an extremely humbling experience. I come from the training as pretty much fundamental sciences. Most of my work has been rather obtuse – structural biology and biophysics do not necessarily translate in most people’s lifetime into anything reasonable, but at the same time, this is this is an experience that I always compare and I know this this is a clichéd expression, but in a certain sense, this has been as if we are building the plane while also flying. And some of the things we do, they are learned and change in midair. We did not… I would be lying to say that we were ambitious enough to imagine that in less than a year’s time of our formation, we would have reached one hundred and twenty five or so centers across, like I said, North and South America. And the number of cases that we have would have gotten to nearly 7000 that this morning. So it has been it has been a complex exercise. There are lots of challenges that we did not have no logistical project management in terms of the legal structures, legal frameworks, and in one sense, not knowing how complex it was, could be called in itself a blessing. Because had we known had I known all the complexities that are involved, I might have had serious doubt on my ability to either put together or deliver on the certain things. But at the same time, it has been well reviewed. We have at this point, we have three year publication, countless editorials. Some of them have upward of several hundred authors. So just making sure that everyone’s name and addresses are correct and they had been entered correctly, that every once conflict of interest forms have been completed and everyone had pitched in their ideas to the manuscript and all those comments have been integrated is is quite an accomplishment. But I think we have done pretty well as reflected in the number of citations and the number of applications that we have already published and the number of manuscripts that got in the pipeline. So it has been well.

Aaram A. Kumar: Yeah, thank you Sanjay! That’s a great overview and, you know, I can’t even begin to imagine it could be quite the daunting experience. When I was in academia and we had to get the forms and declarations done by five or six people, that itself was a mess, so I don’t know what it would be like to do that for one hundred people. And as you said, like, yeah, of course, CCC-19 has been doing with all the citations and there has been some great studies coming out of results coming out of your data collection. So given your expertise in this area, I figured it would be a good start to kick this off by talking a little bit about how high risk populations like patients with cancer, for example, are affected by COVID-19 before we jump into the other topics. So people with cancer, you know, and older patients and people with other serious chronic medical conditions like diabetes or cardiovascular conditions, lung diseases – we know that they are at higher risk for COVID-19 and worse outcomes. So what what are some factors that may be underlying behind the higher risk and worse outcomes that we see in these groups?

Sanjay Mishra, PhD: So what we know so there are facts that we know and there are facts we do not know. What we have shown very unarguably is that the cancer patients who are who were infected with COVID-19, they died at a significantly higher rate. And when I say significantly, it could be three to four times higher than the global average. And while each number may or may not be correctly, but between the two studies that we published, that number has gone higher.

So the Lancet publication that we had in early in May 2010 that had the mortality at around 13 percent, the latest publication that we had, it had slightly higher, at 16 percent. This does not… This may or may not reflect the trend. And we are still looking into the newer trends coming up into the publication that should be in press probably soon. But what we do know is that the cancer patients are especially vulnerable to a disease, a pandemic as it is. There are lots of reasons the cancer patients tend to be immunocompromised to begin with. They have special needs. Oftentimes,  They also are elderly and then they have more contact with the hospital system. What is worrisome is that we don’t know how this will affect in the long run because patients are hesitating or the hospital system is not available for them in their early stage of diagnosis. So, as I said, right now we are talking about the patients who have historical or either current or historical malignancies.

What we do not know is what would happen with this disruption. Would this delay the diagnosis so the patient would have not only been seen, we have had anecdotal evidence is where certain patients were hospitalized for the COVID-19 and during their scans, it was found that they also had a lung cancer. Now, if these patients are being denied the services or because the hospital system is overwhelmed, there would be delay in the follow-ups, there would be delay in diagnosis. How will that affect in the long run is something that we have absolutely no control on at this point. So that is why studies like this are especially valuable, not only to understand and be probably able to give some recommendation at this moment, but also to follow up them in the long run and to see whether the mortalities and the outcomes have significantly diverged from what the trends were, say, a year or two years back, and whether these numbers the diagnosis, because right now we know that some of those supposedly avoidable care is actually being delayed and those delays might have serious repercussion in the future.

Aaram A. Kumar: Yeah, I think that’s that’s a probably unspoken toll of this pandemic, right?  Where we, of course, know about, like you said, the compromised aspect of cancer patients or the same patients that are elderly or diabetes or other complications and them being at high risk. But, then there is this aspect of these people who have chronic health issues that probably need continuous care and screening. And like you said, a lot of them I mean, it is recommended that if you don’t need to go, if it’s avoidable, just don’t go to the hospital. But then that comes at a price. And it sounds like we don’t know what that toll is going to be, but the data collection probably over time will tell us what those excess trends are going to be.

So, yeah, thank you, Sanjay. And so let me ask you this, are there you know, we have general recommendations from the CDC or the WHO and so on, right. So are there any other special precautions that cancer patients would need to take in addition to stuff that is recommended by public health experts like social distancing and mask wearing and so on?

I wouldn’t I am not in the game of recommendation, and I don’t think that we have the ability to actually be able to make any recommendations. I think that is something that unfortunately, as happens, some of those recommendations – they require more confidence in the data. But the one thing we know for sure is that there is no direct correlation between hospital visits and the outcomes in terms of the cancer and COVID-19. So the patients who have the ability and those who have been recommended (to go to the hospital) – they should not voluntarily be avoiding hospitals. I think those recommendations and those decisions have to be made by their oncologists and have to be made by their physicians.

That is very important. Patients should have confidence in the medical science and they should be and it should be the decision should be made by hospitals. At the same time, if the hospital system itself is overwhelmed, then in some cases that decision is being made rather ad hoc and not necessarily driven by any clear-cut guidelines. And unfortunately, those are the the fallouts of a pandemic as severe and as uncontrolled as the COVID-19 is. Then there are some disturbing trends and that are primarily because cancer patients themselves are considered severe. So there is a possibility and there is some evidence to it that the treatments that are being tried, they may be what you can call a kitchen sink approach. There is a dire need to save them. So some of the medications that have come up, they are not always driven by robust science and we don’t have to go on to the history of it.

But hydroxychloroquine was one of those examples. It was not driven by any scientific merit, but by hearsay. And in those approaches, which are knee jerk responses, patients which are already vulnerable, such as cancer (patients), the outcomes can be severely worse than for the normal population or somewhat healthier population, or even if they are hospitalized, the outcomes that we see, they are very, very different from what other general population would have had.

Aaram A. Kumar: That’s that, yeah, I think that’s that’s a great point, Sanjay, because if it’s a healthy person taking a drug that doesn’t work, it might not cause some major harm, but somebody who is already immunocompromised and like you said, have severe health issues, like certain patients with cancer receiving a drug that does not have any major evidence of working – of course, it will cause problems. That’s definitely a great point there.

So I wanted to follow up on the this aspect of the specific risk or needs for cancer patients who may develop a COVID infection. So your group published an article in Cancer Discovery in October that showed that, you know, like you said, hydroxychloroquine does not have any benefit, right. Other than that, and hydroxychloroquine – study after study has shown that it does not have a benefit. But what was interesting to me from your paper was it also said it looked like corticosteroids in terms of all cause mortality in cancer patients who had developed COVID-19 did not have a benefit. But, you know, like corticosteroids, for example, with the large Oxford University run recovery trial and some other studies showed a substantial benefit for patients who are otherwise (healthy), you know, who develop very severe infection, like it was shown that corticosteroids would benefit those patients. So I’m wondering, you know, like it looks like the care of cancer patients who develop COVID-19 infections and others like other patients who are probably generally healthy or does not have other comorbidities – this this could be different. So what are what are some key considerations in that aspect given given this example?

Sanjay Mishra, PhD: So since you bring up dexamethasone, I think this is one of those classic examples where evidence is what should drive our decision making. As you said, it is true that we have seen that the outcome for the use of dexamethasone has been very different, somewhat different from what has been seen or has been recommended by general public.

But then you ask, why is that, why we don’t have a definitive answer for that. But we suspect it could be again, because cancer is already an immunocompromised state and the benefit of dexamethasone might be coming from somewhat of immunomodulation effect. We do know that some of the worse outcomes of the COVID-19 come from something like “cytokine storm” or very high autoimmune kind of symptoms. So it is possible that steroids probably could make potentially these things much worse in the case of cancer patients.

So, again, what we have is the data. We have the guidance somewhat that when a health care practitioner is making those choices, they should look into the data that either we have or other published sources have.

What works for one population may not always work for the other population. And I think this is where the other example that comes, that two big studies – the study in the United States from the NIAID – their trial, suggests that the REMDESIVIR has some degree of benefit, whereas WHO’s big dataset and the RECOVERY trial does not recommend any of them. It does not recommend remdesivir, hydroxylchloroquine, interferon regimens, and all of them because they don’t think that there is a survival benefit in the data between the control group and the non-control group. So I think in a lot of these cases, you have to look at individual cohort and you have to look at what works for one may or may not work as it is for the other.

But at the same time, unfortunately, science requires evidence and science requires a little more patience than an advice which is not based on the evidence. So we are still pursuing on and we are still following up and we are trying to we will probably try to understand. Ours is a retrospective study, so we do not have the benefit of the clinical trials, so we have to believe on what the data is, more on real-life situation. And in that real-life situation, dexamethasone does not seem to have the kind of benefit that has been promised for non cancer patients.

Aaram A. Kumar: Yeah, that’s, I think, a great point there Sanjay, so thank you. I want to say this, that also sort of brings up one of my favorite points about how public is seeing science unravel in real time – like it’s happening in front of their eyes. And that typically you have over time, several years of evidence gathered that goes one way or the other. And in this case right now because of the urgency. So I want to change gears a little bit. So, with the colder weather forcing people indoors and many of us being exhausted by the overall toll of the pandemic, be the other economic or social or psychological, many public health experts like Dr. Fauci are warning us that we are headed for a very dark winter.

However, you know, with cases increasing, death toll going up, but it looks like hope is also on the horizon with multiple vaccines already receiving or about to receive authorization for use across the world.  And it also looks like from the beginning of the pandemic, it looks like physicians are also based on scientific evidence and recommendations, as you mentioned, have learned to manage COVID-19 cases better as well. So we have clearly come a long way from the beginning of the pandemic. So I was wondering, can you talk about some of the therapies that have been shown to be effective? I know we mentioned remdesivir. We have seen evidence in cohorts here, but then in the WHO study, not so much. Corticosteroids, dexamethasone, like you said. I’m wondering, what about antibodies? I know there are some that are already submitted for emergency use authorization with the FDA. And I know Vanderbilt has been very active in this space as well.

So what what role do you think – we can go to vaccines in a minute –  but, you know, before that, what role do you think they will play in getting this pandemic under control?

Sanjay Mishra, PhD: So there are several things that you brought and they each has to be elaborated independently. The overall mortality in terms of the percentage seems to have gone down. And that is most likely because the medical community had learned lessons and has somewhat more experience on handling the crisis. But at the same time, oftentimes, percentage is actually belying factor.

We have to also look at the overall number of burden that we have right now. It is a fact that now that a far more individuals who have been infected, then there were earlier in the pandemic and every subsequent wave has become bigger and bigger. So if you look at that number of deaths now on a daily basis, they are far bigger than what they were reporting at any stage in the past. And that is true for a lot of the places, but more so in the United States. So in that sense, I think we have to be very careful in making assertions whether learning to handle the crisis has helped overall in terms of mitigating the crisis.

And I don’t think we are doing much better job in that sense. And I think, as you mentioned, the pandemic fatigue by itself and policy paralysis added with that and then the economic consequences of this long, year-long pandemic. Now, all of that is making this overall containment of the disease really, really difficult. As far as I’m aware, there is no approved medication to this date and there are recommendations and each of them has only a marginal effect.

So Remdesivir, as one example, the corticosteroids are an example, the antibody cocktails that have been around there, the convalescent plasma and now the vaccine – all of them are a small increment towards having a better handle on the disease, but neither of them are – I hate to use that terminology, but neither of them are as silver bullets to treat the disease. So the only thing that can help us to keep going, probably what has been repeated is flattening the curve. It’s the common sense approach. Until we can find out a method which makes you recover in that sense, or until we can find a situation which is easy to reverse, I think the social distancing, avoidance, and those kind of approaches are going to be the only approaches that will work.

The other things are helpful. Once you have been hospitalized, they can be helpful to stabilize you. But ultimately it is your body which has to fight it out because at this point there is nothing else that is out there. Whatever we have is mostly symptomatic borderline, and each one of them can be questioned whether they are as effective as they say – because you have to remember that some of the authorizations, they are also emergency authorizations. None of these tools have been actually licensed or approved in the classical structure. So whether they are effective and if they are effective, then they are effective in doing what, is still debated.

So I would be a little careful in making assertions that we have any handle on controlling these things at the root level. What we have is a protocol that helps us to help and stabilize patients when they have been infected. But other than that, the disease is still taking its own progression and overall numbers. They are now far bigger today than they were at this time, six months or nine months back.

Aaram A. Kumar: Yeah, and I think, you know, like like you brought up cases and hospitalizations are higher than at any stage in the pandemic, and especially in the US. So, of course, even if we are or the medical professionals are, you know, handling this better or have learned and have more guidance in how to handle it, there are only a limited number of beds and capacity that you can stretch only so much. So, yeah, great points about this. Unfortunately, we haven’t really found a silver bullet or flattened the curve either. So like I said, you know, I’m I’m hopeful in this case that the vaccines that we have, it looks like they have shown good efficacy.

And so I want to talk to you about the vaccines themselves, especially given, you know, you have written multiple articles on this topic that were covered by several big outlets. So I think you’d be a good person to ask some of these questions regarding the vaccines themselves. As we know, a vaccine from a Pfizer has already been – again, I wouldn’t say approved – but for emergency use only. And the other one from Moderna is expected to receive emergency use authorization any time now. So both of these are mRNA vaccines, which is an entirely new technology for vaccine development. So can you tell us how mRNA vaccines work?

Sanjay Mishra, PhD: Yeah. So the Moderna vaccines are definitely a very promising technology in the sense that they actually provide us what has always been called as a platform against a ‘disease X’. The pandemics are not new – within this millennium, this is the third one. We already survived somewhat of a scare from the the first SARS epidemic and then the MERS, the Middle East Respiratory Syndrome. So this is the third one that has caused by the coronavirus. I don’t know whether the increased global travel, the climate change and loss of habitat, all of them mean that pandemics are the last ones the lessons learned from last two pandemics helped us to fasttrack and understand how can we have a reutilizable technology which can be very easily scaled up and can be redesigned for whatever virus or whatever other disease X, which has been a WHO placeholder, can work.

So how mRNA vaccines, work – traditionally the vaccines have been designed either by using attenuated or weakened virus or by taking part of the protein which is on the virus which causes the disease called antigens by the science. Those antigens either you can prepare them from the virus as in case of flu vaccines or in the case you can make them from outside. And by making them artificially and then you add them into certain things and then you give them to the body as a primer, so the body learns how that virus looks like and how that the disease causing virus looks like and then get the antibodies made against this virus, so when you are infected in real life, your body already knows how to handle it. What mRNA vaccines do is that instead of making that protein or making that virus is a tedious process. And oftentimes it is fraught with a lot of uncertainties. As you can imagine, making a weakened virus is very effective/very good as a vaccine goal, but it is risky because you never know whether your virus can revert back to be active again. So that’s always risky, especially for the people who have somewhat of a weaker immunity like older people and the children and pregnant women. Making vaccines from protein is safe, but then the difficulty there is that making a good amount of protein and a good quality medical grade protein is an extremely long term process. And sometimes you don’t know if your protein will work as good or whether it will be of the same kind as the nature has designed in an actual virus. So what mRNA vaccines do is that you take that instruction and give that instruction to the body so it can make its own protein. And mRNA by itself is a very short-lived thing.

So it goes into the body. And current evidence suggests that within a week or so the mRNA itself dies out. But during that process, it does make the protein in the body and there’s enough within that week or so to then start the immune learning process. And the hope is that by doing so, there is enough of that response that then the body can learn and can make good antibodies and good immunity of its own in the long run.

Now, this was an ambitious technology and it has taken quite some time to get perfected for the simple reason – like I said, the RNA itself is very unstable. And then how do you deliver it? Because a lot of the viruses – they are based on RNA. RNA viruses are one of the largest class of viruses. So the body’s natural defense system had worked to actually destroy the RNA as it existed in nature. So the scientists have to figure out a way how you can stabilize the RNA. How do you make it to then dodge the body’s natural defense system, the toll-like receptors, and then after that, how do you deliver them correctly? So there were lots of hurdles, but it is very encouraging and it’s extremely satisfying to see that after several decades of work, the technology has matured out enough that now it is ready to be – it has already passed the Phase three trials. The emergency authorizations has been  forthcoming for the Pfizer vaccine and Moderna is right down the line and most likely within this week it will be there. And there are several more candidates. There is there are other candidates who promise to have a better temperature tolerance like CureVac from Germany, and they claim that this would be available to be delivered even at room temperature. So it may not require that kind of a ultracold temperature.

So it is it is a promising technology. And we will have to see whether the efficacy that has been seen in the somewhat controlled group, somewhat of a restricted age group, will hold its promise in the real-life.

Aaram A. Kumar: Gotcha. OK, thank you for going into that detail and really explaining the intricacies of mRNA vaccine development. And as you noted, of course, it looks like we came up with this or scientists suddenly developed a brand new technology but as you said, the groundwork has been laid decades ago and we are building on it. And it’s really exciting to see it come to fruition. So you did mention the other more traditional setup of making proteins that could be effective as vaccines, but then, of course, comes with the challenge that it would be difficult to produce and produce good quality proteins that can act as vaccines.

So as I understand, there is, you know, a third vaccine that is pretty far advanced in terms of the clinical trials and probably has a good chance of approval. So the one from Oxford University and AstraZeneca, it looks like it fits that more traditional mold and the temperature factor, like you said, Pfizer and Moderna vaccines need to be kept that really cold temperatures and this one can be more normal temperatures.

It looks like it’s a little less effective, but can you tell us, you know, in terms of delivery and capacity and all these storage and these factors, what role this vaccine can play in our fight against COVID-19 as well?

Sanjay Mishra, PhD: Yeah. So the AstraZeneca vaccine, that is also a very exciting new class of vaccine. And it is actually, while it is analogous to the traditional approaches, it is not traditional at all. In fact, if it makes it to the approval process, it will be the very first of its own kind. So how does that work is that it’s a chimpanzee cold virus which has been designed or modified not to be able to grow. So remember, this is a chimpanzee virus, which means that it does not affect humans as it is because viruses have their own specific host requirement.

And on top of it, it has been modified to not grow in the natural system. So it grows only in the test tube, but it does not grow into the body. It is replication-deficient and then most of its genome has been removed other than what is needed for it to act as a virus. So it can and then you take an external protein, in this case, the Spike protein of the SARS-CoV-2. And then when you design it into this virus, the virus the chimpanzee adenovirus then behaves (mimics) like a SARS-CoV-2 in the sense that the spike protein is coated on the surface and that’s what you are giving.

So it’s an extremely ambitious kind of a vaccine. It is a very new vaccine, very similar to the mRNA vaccines in the sense that it’s a platform which is now seeing its first day in the real life.

As far as the efficacy is concerned, I don’t want to get too hung up on it. It is really difficult to compare apples to oranges. And we also have to remember that benchmarks that were set for the COVID vaccines – the expectation was 50 percent and they could have been even lower than 50 percent, because at this point, when we have a pandemic wave, what we want, the first thing is, again, going back to the classic flattening the curve; we want to slow down the progression of the virus. And if we can slow it down sufficiently, we can win the we can slow down the progression enough that we can buy sometime. There are 42 vaccines in the advanced stage of development and there are several hundred in the pipeline. So if we can buy some time, we can then either develop toolkits; maybe there are some medicines that can come along, maybe there are some antibiotics that can help us better.

So we shouldn’t be getting too fixated on the numeric difference between the efficacy of, say, Moderna vaccine versus Pfizer vaccine versus AstraZeneca vaccine. And then there are some that are coming from Johnson & Johnson and Sanofi. They all are very exciting technologies and they tell us that given enough resources and money and also with enough excitement in the scientific community, we can we can win these things. So it’s reasonably efficient.

There is some doubts on the numbers that have been put forth, but at the same time, the data is now available into a peer-reviewed journal, and when I read those numbers, they seem they look very promising. There are some questions that they need to answer, and I think they are still in the testing phase. But the hope is that if those numbers, as they have been published, they hold correctly in the more extended trials. It is a very promising vaccine and like you mentioned, because it does not require that extreme storage requirement.

It definitely has a very good promise, especially in those circumstances where these cold chains are difficult to maintain or if we need these vaccines, because we don’t know at this point any of these vaccines, because it’s been such a short time, we don’t know what the duration of the immunity is. So if we need multiple immunizations, I think the question of what is available to which age group and which population group and which region, I think a lot of these candidates will all come handy in that time.

Aaram A. Kumar: That’s yeah, I think a really good point about not getting hung up on the efficacy, especially given where we started based on our expectations, was that 50 percent cut off and now we have these different candidates all really blowing those expectations out of the water, at least in very controlled trials. So if that can hold, that would be really amazing. And it also looks like both the Moderna and Pfizer ones, a lot of those initial doses are going towards more Western countries, while the Astra Zeneca vaccine  looks like it will also be going to other other places that really need the vaccines as well, like India. So I guess, again, we need all the help we can get.

Sanjay Mishra, PhD: And even in that class, the the approach that the CureVac is using is very interesting. One that they claim, of course, they are still in the phase three and has been tested only in Germany, but it claims to have three months of stability at the normal cold refrigerator, just the grocery style or deli style of refrigeration. So even if the mRNA vaccines are the way to go, that one will have a pretty good chance of being available even in the low-resource places.

And then they are they are trying to be in collaboration with Tesla. So instead of having this large cold chain – you have to remember that one of the advantage of the mRNA is that it’s rather easy to produce, it’s more of an industrial product than a biological product – so what they are trying to do is that they’re trying to have these mRNA microfactories. And the hope is that with those small microfactories, you can actually produce them somewhat closer to the end user.

And then with this very efficient stability of about five degrees Celsius or about forty one degrees Fahrenheit above zero, you can store it well, you can produce it locally and you should be able to distribute it to even in the resource limited region. So I think that hope is on the horizon. One thing I want to highlight is that I think in one sense – and it’s very morbid to put it that way – but we seem to have hit the jackpot in terms of the antigen selection.

A lot of the vaccines fail because vaccine is not something you develop on the textbook. You hope that your antigen selection, like in this case, the Spike protein would be the one where a lot of the success will rely on. What is really encouraging is that all of these vaccines have focused on the spike protein as the primary antigen, and they all have shown extremely good efficacy.

Like I said, we don’t know the duration yet, but we hope that the duration would also be good. But even if it’s not in terms of the efficacy, they are all very good, very efficacious vaccines. So I think because of all these candidates, I’m sure there would be candidates which would be suited for different environments, different affordability and different regions. So they all should do pretty good.

Aaram A. Kumar: That’s definitely important because we have been trying to build a vaccine for HIV for a while.

Sanjay Mishra, PhD: Yeah. And also, Zika, I mean, the AD has always been suspected to be one of the problems. Nothing that has come out from all these trials suggests that we have to worry about that. And so in that sense, you really don’t know early on, you don’t know whether any of those risks will pan out.

Aaram A. Kumar: So we we already talked a little bit about, you know, how these vaccine candidates that we have seen are really effective. But I want to touch on safety for a moment. Because that’s that’s a concern for a lot of people. So let’s talk about, you know, like how does the safety profile of these candidates look like, you know, compared to, say, historically what we have seen with other vaccines?

Sanjay Mishra, PhD: None of the vaccines that are and they have been tested. If you take the overall class of the vaccine, not one, but in entirety, the number of people who have been tested for with these vaccine candidates is very, very large. I think in that sense, it is unprecedented. Never before, vaccines have been tested on that large number of people before they were released. Nothing so far that I’m worried that there is a risk. All vaccines have some inherent risks. And most of what these vaccines, which are entirely new vaccines, I think the vaccines have proven reasonably safe, given what we didn’t know about these vaccines.

There have been some discomfort, but most of those discomforts have disappeared on their own. And no one or very few of the volunteers had needed hospitalization because of the vaccine. So there are recommendations because they are untested. Unfortunately, the current guidelines is that if you have a history of allergic responses, if you have this history of anaphylactic responses, if you are overtly sensitive or if you are overtly allergic, you should not be given those vaccines. So those will remain in place until we understand more about it.

But within the last one week of them being available in real life in the U.K. and now in America, in real life, and even in the during the phase 3 and phase 2 and phase 1 trials, there is nothing that has come out that should worry anyone. I think they are very safe vaccines. In between your alternate – given that this pandemic has such a high effect on people’s life, I think no one should be worrying about the overall safety of the vaccines.

Aaram A. Kumar: Yeah. I saw that there are so far away three reports of severe allergic reactions. But like you said, in real world, it has been administered to probably thousands of people at this point.

Sanjay Mishra, PhD: And yeah, I wouldn’t call them severe allergies. What they have is that they had allergic responses, but none, to my knowledge had required hospitalization.

Aaram A. Kumar: So, you know, that that brings me to another interesting point. There, of course, is vaccine hesitancy or the anti vaccine movement. It has been around for a while now and there have been a lot of misinformation that already has caused people to have some sort of uncertainty about getting vaccinated. So here it is, basically because this is a new class of vaccines, they’re having their own specific – for the lack of a better word, I would say – disinformation campaigns running around that I have seen both are being shared profusely online or as through word of mouth from people.

So I wanted to touch on a couple of those real quick – One of them is that this being an RNA vaccine can cause a change in the DNA of the recipient. Or the other one being that COVID-19 vaccines can potentially cause female fertility issues. I was wondering if you could maybe take a minute or two to quickly dispel these misconceptions.

Sanjay Mishra, PhD: Yeah, the hesitancy against vaccines is not new, going back all the way to Ben Franklin, who decided not to vaccinate his son, and then he passed away and he regretted it. So it is not a new thing. It has it is a standard feature of our society. If I look at the flu vaccination, the vaccination coverage has never reached the 50 percent of the population. So we have to be cognizant of the fact that people are hesitant to vaccines, not justifiably, but at the same time, we don’t make the society, we live in the society that we have.

We can convince people that these vaccines are safe. A lot of their questions need to be heard and they need to be answered. So the two that you brought, I think both of those are only the tip of the iceberg. People have had multiple questions. And I would like to have a forum for all of us should be actually pitching into asking and listening, asking questions and listening to the to the concerns that they have. So the fact that the mRNA is can be somehow can modify somehow the DNA, I think people should allay their fears. mRNA is like a Snapchat message. It does not stay for a long time. It does what it does and then it goes away. In fact, that was the challenge that these vaccines have faced for almost a decade. It was very difficult to make the RNA even last long enough to be able to do something. So you can’t have something which is so fragile that it needs extremely cold temperatures to survive, then also be able to do long term, long term changes.

The mRNA has no ability to convert back into the DNA. There are no tools for that. It is injected and it stays in the cytoplasm and it cannot have a mechanism that there is no signal for it to carry from cytoplasm inside to the nucleus where your chromosomal DNA sits. So, one, it cannot go there. It cannot change. There are no natural tools available for this mRNA to be converted into DNA except for those rare circumstances, if possible, for somebody who has a persistent retroviral infection, such as, say, an HIV.

And even if that were to happen, the DNA itself does not get integrated in those cases. It requires support of other tools which are just not existent in the mRNA vaccines. So the mRNA by itself doing a change or converting into DNA and then causing a gene modification is just a work of fiction and there is no science behind it. In fact, some scientists would like to have those efficient tools to be able to do gene changes because then probably you can use some of these tools to make changes in the cancer cells.

Unfortunately, it is not possible and that is why treating cancer has been so difficult, because we don’t have the correct tools. In fact, mRNA vaccines were first being developed exclusively to mitigate cancers and to be a cancer therapy.

And it has been long that we don’t have the tools to do those long-term changes. So, I think people should not be worrying so much about that. I’ve heard the stories about the syncitin-1 and that little homology of 8 to 10 amino acids that exist between syncitin and the spike protein. The reality is that most people who understand these things would realize that that small homology exist between any two unrelated protein. So the idea that somehow that little stretch of spike protein has small homology, it’s not identical, it’s a good homology, but not a lot of homology would have any effect on the behavior of the syncitin protein or syncitin-1 is just not correct, because if that be the case in these large number of patients which have been tested and those patients who have suffered, we would have seen a significantly high amount of effect, which is not what we have seen. Now, when you have an infection, a natural infection, yes, oftentimes, the pregnancy is suspect in those cases. And the first-term pregnancy and the losses are pretty high. But it’s a correlation and not a causation.

So, the idea that somehow giving an mRNA vaccine, which has a small degree of homology with the protein in the in the fetal development or in the in uterus will have any effect, is just not correct. So I think people should allay the fears. They should trust the medical community and they should trust the public policy developers and go from there.

Aaram A. Kumar: Yeah, thank you and I think from what I have seen for regarding specific COVID-19 infections in, say, pregnant women, there simply hasn’t been any level of concern there or a matter of causing miscarriages or causing problems to pregnancy so far, like even in the case of real COVID-19 infections

Sanjay Mishra, PhD: Yeah, they are not significantly higher than other infections. Most infections make gestation difficult to begin with. So it is not surprising, but it is not the risks are not significantly and higher than and the data does not exist to support any such.

Aaram A. Kumar: OK, yeah, thank you, Sanjay. And so, you know, I also want to take a few minutes and quickly talk about what lies ahead, right. And so what percentage of the population needs to get vaccinated for us to, say, achieve herd immunity or reach a point where we have the pandemic under control?

Sanjay Mishra, PhD: The estimates are a little difficult to make. The general rule of thumb had been somewhere around 60 percent. The problem with that is that we don’t quite know exactly what the R-nought (R0) is, so we don’t know exactly how many people each infected person actually infects. So it is it is difficult to actually put a magic figure on that. But I think it can be safely assume that if it could get even to the level of the flu vaccine level, which is only 50 percent to 60 percent of the coverage, I think that would be very effective.

It is difficult to know ahead of time what would be the availability of the vaccine, it is we don’t know what the compliance would be and also we don’t know what the durability would be, how frequently. But I think one of the somewhat of a concern has been that most of the vaccines that we have, at least on the on the leading edge of the approvals, they all require dual doses. Not to say that the one dose is not sufficient. They still have a very good efficacy even at the one dose. But they have been tested and they have been recommended to the two dose label. Compliance of those two doses would be a little difficult. So it is hard to imagine what would be overall acceptability of the of the vaccine once they are available and when they are available for the general public, how many people would actually be willing to take them? But I think at least one dose regimen of a lot of these vaccines, if we can achieve somewhat at 50 to 60 percent, well, that would be really, really recommended.

That would be a safe point than if – imagine that we would have recovered ourselves from this safely.

Aaram A. Kumar: Yeah, I guess that that goes on to tell us, you know, that emphasizes the importance of not being complacent just because there are some good vaccine candidates here. So in that case, I would think we wouldn’t be maintaining these a lot of these current public health practices that we are using to tackle the pandemic, like social distancing, mask wearing, and avoiding crowds.

So, the other thing, I guess a little bit of a futuristic question in this case is these emerging vaccines, like you said, you know, they would be the first of their kind to be approved. They have been quite the accomplishment in vaccine research itself. If they are successful in the larger population, once we are administering them worldwide, do you anticipate this you know, this technology to sort of revolutionize vaccine development and targeting other diseases using this technology?

Sanjay Mishra, PhD: Yeah, no doubt about it. I mean, we we have achieved so much in such a short time, primarily because so much legwork was already done. The relative quickness by which these vaccines have come along should not fool anyone because we had already almost gotten foot to the door (earlier) when the last crisis has come. The spike in the Moderna candidate was almost the same structure and same design, which was already done totally by the candidate in the NIH.

So it is not like that that these things have just come out of the hat. They were there. The platform was developed. A lot was learned from the last two pandemics so we could make it that very quickly as possible. So as far as the platform goes, I think we have these technologies have now reached their maturity. They are what would happen from this round is that we will have not only seen their benefit in the real-life, but we would have evolved and then developed the structures which support that kind of a thing.

But then whether this would be a silver bullet, again, it is very difficult. We biologists don’t have a crystal ball. What the next pandemic will come would bring its own challenges. It is possible that a next pandemic could be much less severe and would not be as infectious. Maybe we would have learned our lessons and how to contain it at the point of its origin or then from spreading. Maybe we would have begin to have better trust on the public health officials, so when we are told to stay put and not be out there spreading the disease during the Thanksgiving and the Labor day holidays and the Christmas holidays, I think that would have helped us a lot. Maybe, maybe we can stop damaging the environment, which then causes sometimes, these human animal interactions to be far more. I think that is something that has to be also. So it is difficult to imagine what the next challenge would come. I think each pandemic has its own survival. What causes one would not necessarily be the one that will happen the second time. But it is true that these vaccines have definitely come to maturity. And I think what we will learn from here will be useful, exceptionally useful for the next experiences, and especially for the mRNA vaccine. They have enormous advantage. They are very easy to tailor make for whatever comes along, they are agnostic to practically everything else. And there is a hope that some of the safety parameters that we are seeing would be agnostic to each one of them, because it is possible that some of the side effects that we are seeing or some of reactogenicity that we have seen is for the lipid base and the lipid nanoparticle.

If that be the case, then it would not matter whatever vaccine it is, whichever, because all we need to do is we change the mRNA and it would have exact same efficacy and it would have exact same safety profile. At the same time, I want to reemphasize – we seem to have hit the antigen jackpot. So whether we will be able to replicate the success next time, nobody knows, but especially for other ancillary benefit, I think they do open a gate for a lot of promises and success going forward.

Aaram A. Kumar: That’s that’s great. Sanjay. Really appreciate you answering all of these questions. And we have covered quite a few topics today and this has been an excellent discussion. I really appreciate you taking the time today to share your insights with us and providing us a ton of really useful information. So, thank you very much, Sanjay, on behalf of Sciencera, and me, and our audience. We really appreciate your time.

Sanjay Mishra, PhD: Thank you. I really appreciate it. Thanks for the chance.

Aaram A. Kumar: Thank you.