Emerging COVID-19 challenges: long-COVID and viral variants

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RICK WEISS: Thank you, Josh. And welcome, everyone, to this SciLine media briefing. A quick introduction for those of you who are not familiar with SciLine. We are an editorially independent, free service for reporters and scientists with a mission of helping reporters get more research-backed scientific evidence into your news stories. We’re based at the nonprofit American Association for the Advancement of Science. And we’re supported entirely by philanthropies. And we offer a variety of free services that I encourage you to check out on the sciline.org website. But I will mention just one of them. In addition to these media briefings is our matching service through which you can get in touch with us with a very quick form. Let us know what kind of a story you’re working on and what kind of an expert you need to talk to. And we have a large database of excellent scientists who are great communicators to whom we can connect you on deadline or as needed to help you with your story.

Today’s media briefing is an opportunity to get the facts on two aspects of the ongoing COVID-19 pandemic that are starting to look like significant hurdles for the year ahead. The first is this seemingly unstoppable emergence of new variants of the causative virus, SARS-CoV-2. As we now know, some of these variants are just different enough in their structure and activity for them to avoid full-blown attack by even the best-trained immune systems, that is, immune systems of people who have been vaccinated or people who have antibodies because of previous infection by a different variant. So we’ll take a look at what this reality portends for getting out of crisis mode in this pandemic and getting back to some semblance of societal normalcy. The second hurdle that we’ll get into today is this syndrome sometimes known as long COVID. It’s almost a cliche at this point to refer to this emerging syndrome as poorly understood and a bit of a journalistic cop-out to leave it at that. So we’re going to help you understand what is understood about this, even if it is a little bit thin still, so that you can share those details with your news audiences.

I’m not going to take time today to do full introductions of our two panelists. That information is on the website, sciline.org, under briefings. I will just say here that we will hear first from Dr. Hana Akselrod, assistant professor of medicine at George Washington University School of Medicine and Health Sciences. She’s going to speak about the different variants of SARS-CoV-2 and what the evidence shows about how these have spread around the world and across the country, and why some of these variants may be of particular concern. And then second, we’ll hear from Dr. Christian Sandrock, who is a professor of medicine and director of critical care at the University of California at Davis School of Medicine. He’s going to provide an overview of long COVID, including a sense from recent studies of how common it may be, how it’s playing out in patients, and how those affected may find some relief while research into this syndrome continues. While they’re talking, feel free to start sending your questions in at the Q&A icon at the bottom of your screen. And with that, let me turn it over to you, Dr. Akselrod.

[0:03:21]

HANA AKSELROD: Thank you very much for that introduction, Rick. I will just share that it is both thrilling and deeply unusual as an infectious disease physician to talk about viral variants and viral evolution, which until 2020 was a bit of a niche area. So thank you all for joining us and for delving deep to understand these issues. So I would ask my counterparts who are sharing the slides for me to bring up the first slide at this point. Thank you. So the reason we are here discussing this at all, the reason we have a pandemic is that coronaviruses are notorious for being quick to mutate. They do this, for comparison, a bit slower than influenza, but faster than other familiar viruses such as measles. And what mutation in the virus means is that when it replicates, random errors happen in its genetic sequence. These errors correspond to changes in its 3D structure when it is fully assembled.

The relevant version of SARS-CoV-2 is the spike protein, especially the little green bit in the illustration on the right, which binds to the receptor on human airway cells called AC2, which act sort of as a lock and key. It opens the gateway for the virus to enter our cells, and there it starts its reproduction process, takes over the cell, breaks it, and creates the inflammation, the damage and the symptoms of disease that we see in people sick with COVID-19. The immune response to this takes some time, and eventually the body will produce antibodies that will block the spike protein from binding to the receptor and doing damage to further cells. And those antibodies and this memory will persist, and hopefully the next time the body encounters a version of this virus, the antibodies will block its spike protein. And it doesn’t get to enter, and the disease never occurs. So that is the theory behind how antibody formation, either through natural infection or through immunization, can prevent cases in the future.

So what happens when the virus mutates? Well, most mutations are random errors, and most of them actually don’t benefit the virus. Some may break it and make it non-functional. But once in a while, a mutation will arise that is of benefit to the virus. Maybe it makes it bind to the human receptor more effectively. Maybe it results in more copies of the virus being produced, making for higher viral loads in the nose and the airways of people who are infected. This process has been going on throughout the course of the pandemic. It’s been described in different parts of the world. And one variant that we’ve heard about in late spring and summer 2020 was called D614G. It emerged or seems to have emerged in Europe and then was detected in many of the cases on the U.S. East Coast in spring and is thought to be responsible for why there was such a steep rise in cases in those areas before strict public health measures were implemented. This variant, D614G, was more infectious and possibly made for higher viral loads and was able to spread faster and outcompete the original virus that was sequenced in Wuhan. So we already have had to deal with changes in viral populations. The aspects of variants that are particularly concerning is some of them may be easier to transmit or may cause more severe disease or may evade immune mechanisms produced from prior infection or vaccination.

So in the next slide, I have put together a table of the three key variants of highest concern right now. These are not the only variants out there. As I said, the virus is constantly developing new mutations, and some of them will persist either on a local basis or with the potential for further spread. So this is a situation that needs to be monitored constantly. So through some of the monitoring mechanisms, which involve genetically sequencing the virus and sampling it frequently on the population level, in late fall/early winter in the U.K., a variant called the B.1.1.7 was described. When we discuss different variants, we can refer to them by the name of the location where they were first identified, but the more scientific way to do so is to refer to them by their viral lineage, or what branch of the virus’s family tree they come from. They can also be described by particular mutations they may carry. And different variants or lineages will have more than one identifying mutation often. So the virus that was first detected in the U.K., SARS-CoV-2 B.1.1.7, bears several mutations that appear to change the shape of the spike protein to make it just a little bit more transmissible. In fact, 50 to 74% more transmissible based on some studies. There have been multiple studies discussed in scientific meetings in recent weeks, and some of them are going through the peer review process, moving from preprints to publication as we speak.

Some of the key issues of concern with B.1.1.7 is that it seems to cause more cases in children compared to the generally circulating or wild-type virus. It may carry higher odds of mortality, and it may lead to higher or more persistent viral loads in airways, explaining why it is more transmissible. In the U.S., cases have been detected, as of this morning, in more than 40 states, and they double every 10 days or so. So this is a variant of emerging concern for us. There is ongoing research into it, how it interacts with immunity conferred by the vaccines that we have been using, the Pfizer and Moderna mRNA vaccines. The next variant of concern was first described in South Africa. It shares some mutations with the variant described in the U.K. It is from a different lineage, B.1.351, and this emphasizes the point that different mutations can be selected or emerge independently in different parts of the world so long as they carry a benefit to the virus. So the virus gets an advantage from them and kind of gets a reason to keep them as it spreads.

So the B.1.351 variant — it is unclear how much more transmissible it is compared to the base line, but it’s concerning because it seems to evade the immune response, to some extent, from existing vaccines, including especially the AstraZeneca vaccine, which was planned for wide distribution in many countries, including South Africa, as part of its public health push to bring viral transmission down. So South Africa and other countries may be reconsidering which vaccines they use depending on which variant is dominant locally. In Brazil, there is a variant called P.1, and it has only been detected in a couple of U.S. states for now, but we’re also watching it closely. The P.1 also shares mutations with B.1.351 and also has the ability to evade antibodies from prior infection. One very concerning epidemic of this variant seems to have occurred in Manaus, which is a city that previously had very widespread transmission of SARS-CoV-2 earlier in the year, and more than two-thirds of residents were thought to already have antibodies against the previously circulating version. So this really makes us worry about SARS-CoV-2 and COVID-19 becoming an infection that can come back year to year so long as it makes just enough changes to its surface to avoid our immune system. In the next slide, I outline a few points that are foremost in discussions of both individual responses and family and community responses in the next few months.

We have a window of opportunity in the U.S. as our cases are going down steeply after the holidays and as we finally are rolling out our mass vaccination plans. We have a window of opportunity to reduce viral transmission before the new variants spread or new variants arise locally. We are going to need to keep paying close attention to personal protection, to ventilation, to effective masking, to reducing public gatherings and doing all the public safety measures we have been doing until we can bring transmission down to manageable levels at which public health officials and local authorities will be able to keep track — test, trace, isolate people who are contagious and support them through it despite new variants arising. We will need to learn from mistakes of months past, and we need to use our vaccines because they are still effective. Now, if we think about that three-dimensional response and interaction between antibodies and the spike protein, individuals will vary in which side of the spike they will create the antibodies for, what exact part of the virus their immune system blocks. So mutations in one part of the spike may or may not change how an individual’s immune system reacts to it. We need a lot of study on it, and we need to be aware of the variants that have the ability to escape antibody from prior infection and immunization.

This brings me to my last point, which is that public health laboratories and labs and researchers that are able to perform genomic surveillance or look for those concerning mutations in the virus that circulates — they are absolutely critical resources. Many of them have been operating on a shoestring budget or had staff that are themselves depleted and exhausted over the past year. And we really need to bolster this capability in order to meet the challenges from new variants of the virus. Thank you very much.

[0:14:47]

RICK WEISS: Thank you, Dr. Akselrod — fantastic. And I see we already have a few questions coming in on some of this, which we will get to. Meanwhile, let’s switch over first to Dr. Sandrock. Thank you.

[0:14:58]

CHRISTIAN SANDROCK: Great. And hopefully you guys can all see the screen here. And if you can’t, let me know. And I’m Christian Sandrock. I’m a pulmonary and critical care and infectious disease doctor at the University of California, Davis, if you — as you heard of. And talking a little bit about the long-term effects of COVID has been a bit of a challenge. And, you know, to say it’s poorly understood is true, but there’s a few things we’re sort of working in a direction towards. And the first thing I want to mention is a little bit about the naming of it. And this is not just only my pet peeve. I know in the beginning, as infectious disease physicians, we all spent times just explaining what’s the difference between SARS-CoV-2 the virus and COVID. Particularly when our colleagues would call and say they’re COVID-positive, it drove a lot of the infectious disease physicians crazy.

But the importance of this is really that we want to let everybody know that when you have what’s called a post-acute COVID syndrome, these are persistent symptoms, but they’re not infectious. So when you hear things like long haul COVID, COVID long haulers, continued COVID, post COVID, that really doesn’t give us a sense, OK, how far out are you? Are you infectious or not? Is the virus actively replicating and driving a lot of the disease we see? And I think that becomes important. And really, we’ve sort of settled. And I would say the scientific community hasn’t fully settled, but we’ve sort of settled on this idea of either post-COVID syndrome or post-acute COVID syndrome because that lets us know that, hey, the acute phase of the illness is done, there’s persistent symptoms, and you’re no longer infectious. So generally, we’ve kind of settled on that post-acute COVID syndrome, but you’re going to hear a lot of variability, certainly among the public. And particularly in social media accounts, this idea of long haul COVID has really taken on.

But it’s more of a misnomer because it doesn’t really rely on the fact that this is persistent symptoms that really are not infectious and really residual leftover from the infection. So the question is, how common is this and how sick do people get? And there’s been a number of studies. Probably the best study is actually in Lancet, which came out recently and was from Wuhan and followed most of the people hospitalized early in the phase of the pandemic. I just chose this one study here. And I just want to mention a little bit about it because it sort of has both hospitalized and non-hospitalized patients and really highlights the effects that we’re sort of seeing with this post-COVID syndrome. So this study was predominantly from Europe and the Mediterranean basin. And if you notice, it mostly had patients that were in the ICU and were inpatients, also had some non-hospitalized patients that were symptomatic. And the reason that’s key is we’ll mention in a second. But when you’re in the ICU, whether it’s from COVID, influenza, whether it’s a trauma, whether you have acute lung injury from another process, that prolonged ICU stay — that includes, you know, mechanical ventilation, life support, sedation, pain management and so forth — can have its own effects. And very clearly in the literature over the last decade, we’ve learned that ICU stay has its own effects. And that may be driving the process in many patients in the ICU and COVID, but we’re also seeing a group of patients who actually have disease that’s present actually without hospitalization.

So many patients who come in are not seen at all, you know, obviously, by a physician, that are at home, but symptomatic. They have persistent symptoms associated with our COVID. And that is actually really quite unique. And we don’t see that as much with influenza and other viral infections. So in this study, about half of the patients, 58% in the critically ill, had symptoms that persisted out beyond 90 days. If we look at the Wuhan data, that actually shows that two-thirds and up to 75% actually in some subsets had symptoms now at 90 days. There is a telephone survey at 180 days from the Michigan Department of Public Health that actually looks at symptoms being persistent in about two-thirds of people at 180 days. So it gives us a sense that, you know, quite a few people are having these persistent symptoms. And the most common things we see obviously are fatigue, shortness of breath, loss of taste, loss of smell and then a number of different testing abnormalities that come with that. And I’m happy to talk about that a little bit down the line.

Now, the symptoms we see with this are pretty broad. But interestingly enough, what drives them is less broad. But you can sort of see here — and I won’t go into these in great detail, we can talk about it more — but what’s probably getting the most attention is some of the chest pains, shortness of breath, obviously rash and loss of hair, and then more particularly, a lot of the neurologic and constitutional symptoms — so loss of taste, loss of smell, brain fog, people feeling that they’re just not themselves, a ton of sleep dysregulation and then depression and anxiety and changes in mood. And these are all really discrete issues that we’re certainly seeing. So what’s really driving this and where are we at? And there’s really four main theories that we have. And it really maybe all of one that’s driving it in one patient, it might actually be a mix of others that are driving it in a patient. And that’s really the hard part, is to figure out what’s leading to most of this. So the first is that you had a prolonged ICU stay. And these are all complications that are well-known. So, again, if we follow patients without COVID at the six and 12-month period after a prolonged ICU stay, we see that they have fatigue, forgetfulness, neurocognitive deficits, lots of anxiety and depression, post-traumatic stress disorder. We know that exists. And by — we’re working with our patients in the ICU, minimizing sedation, minimizing their — you know, their deconditioning in their bed-bound nature, engaging in their — participation in their care and physical therapy has improved outcomes.

So we know that that’s the case. So many of their patients were seeing, particularly in this study, is showing that an ICU stay is a risk for having post-acute COVID syndrome. We know that that in and of itself may be driving a lot of this, and it might not actually be the virus or the effects of the virus that are driving it. The second is what we call microvascular disease. So we know when patients have acute COVID, the likelihood of having a clot in their major vessels, a stroke, pulmonary embolism, a heart attack, all of those things are present. We also know that they get a lot of microvascular disease, so disease in the smaller capillaries in the body. And that leads to a lot of the profound issues we see in acute COVID, so, for example, chest pain, decreased oxygenation, patients breathing fast, their, you know, their brain, their GI tissue, all of it not having the blood flow that they need. But what we’re finding is that in this post-acute COVID period, they have microvascular disease that seems to persist for months and months. And that drives a lot of the symptoms you see — chest pain, shortness of breath, very high heart rate that, you know, is literally, on walking a few steps, their heartrate hits 140, low oxygen levels, a lot of the brain fog as their brain tissue doesn’t get the blood flow, fatigue, inability to exercise.

And we actually can find these abnormalities on tests. So if we — and I can talk more about that in the after period. But if we actually do, for example, pulmonary function testing, we might see that the diffusing capacity or your ability to extract oxygen and release carbon dioxide is actually abnormal, suggesting that’s microvascular disease. There is an autoimmune process that happens. So we have looked at patients in the acute phase who have extreme forms of inflammation. We do find that they then have what are called autoantibodies. So, for example, the antibodies we see in rheumatoid arthritis, lupus and other autoimmune diseases now become positive when they were not before. That may drive a lot of the effects we see of sleep disturbances, chronic fatigue, overlap symptoms, depression and so forth.

And then lastly, we know there’s a direct infection of the virus. Now, that drives a lot of the microvascular disease, but we know — and there’s going to be some emerging data that really looks at the virus affecting the CNS, so particularly, your loss of smell, your loss of taste. Some of the neurocognitive deficits and psychiatric issues we’re seeing might be actually the direct effect of the virus on CNS tissue as well. So what are some of these things we can do? And then I promise I’ll stop talking. So, you know, obviously No. 1 is improve living. And part of that is really recognizing that this is actually a disease syndrome. So what we’ve learned over time, particularly with patients with chronic fatigue, is that many physicians and many colleagues and workers will actually dismiss these symptoms. So — oh, you’re coming back to school; you’re coming back to work. You’re saying you’re fatigued and tired; you’re depressed. You’re just kind of dogging it. This is not really real. This is more psychiatric. We’re actually really learning that this is actually a real syndrome. And if you’re tired and you’re slow and you’re depressed and it takes you longer to do things, validating that disease with our patients, some of the first steps we need to take.

And then improving their structure of their lives — so that may mean they need more time to finish tasks, building in mind exercises, improving reading, having steady activity that’s monitored. So that might be yoga, meditation, regular walks, quiet time during the day — improving sleep hygiene is essential — and nutrition. If patients do have a predominant symptom, we need to check it out, and we need to treat it. So, for example, if depression is a main feature, these are not people that we say, oh, it’s post-COVID, we’re just going to ignore that. We might actually treat you with an SSRI or an antidepressant medication. We might work at managing how that depression may be, and that may be a direct effect from the virus. It might actually be effective some of the issues you have from the virus. So, for example, if you lose taste or smell, which I see in a lot of my younger patients, they can’t taste coffee every day. And you can imagine if after three or six months, I can’t drink a cup of coffee and it tastes like warm muddy water, I’m going to be pretty depressed. And I think a lot of our patients have this reactive depression to that. And then there’s anticoagulation anti-inflammatory agents like steroids and a number of other immune modulators which have potential.

But right now, the real treatment side is we do not have any clear course of action that we have. We know recognizing this disease, improving living, treating areas that have obvious areas we need to treat. We will go down those avenues. And if there’s a larger overarching medication or, you know, class of medications that will work, we don’t have the data on that yet. And I know there’s a lot of research moving in this direction. The NIH has actually just released some funding opportunities to look exactly at that, and those are some areas that I think many of us in the academic world are going to look at. And with that — if you have any questions, here’s my email address. And I think SciLine will have all this up. And you can call our public affairs people because, you know, as my wife will say, there’s many things I don’t know, and they will at least find someone that knows something here or otherwise. So with that, I’ll stop sharing and turn it over to Rick.

[0:25:21]

RICK WEISS: Fantastic. Thank you both — so interesting and well put-together presentations. Really appreciate those introductions.

Before we start opening it up to questions from the reporters — and I’ll remind you all that you can go to the Q&A tab at the bottom of your screen to submit them. We have some stacking up already. But I want to just have one question from the moderator here to get going, and that is to ask you both to think for a minute about the news coverage you’ve seen over the last months in the areas that you work in and something that you think you can share with the reporters on the line — maybe it’s something positive that you think is getting done right and you’d like to see more of, maybe something a little bit off that you think is a chronic mistake being made in the media that you’d like to get a word out there and maybe stop it or get it fixed. Maybe it’s something specific to your field or something larger about COVID generally. But any tip up or down that you’d like to give to get us started — and I’ll start with you, Hana.

[0:26:22]

HANA AKSELROD: I’ll start by unmuting myself. That’s a start.

[0:26:24]

RICK WEISS: That’s always a good start.

[0:26:27]

HANA AKSELROD: You’d think a year into this, we’d have the handle on it. So I’ll share something that is fairly surreal but positive, which is — and I’m stealing this comment from somebody on Twitter that I read. Before this past year, I couldn’t pay my students to care about test sensitivity and specificity, virus site-specific mutations, protein folding. And we are having a conversation in the public sphere about this in real time now. I think the learning curve in science literacy and the appreciation for understanding some of the fundamentals of modern cellular and molecular biology and epidemiology, that’s been a huge positive. Those are — to me, they’re beautiful areas of science. And I’m thrilled to get the chance to talk about them. But the surreal part is it’s in the middle of a pandemic, and our future human lives and life as a society depends on the answers.

The other key piece of coverage over the last year that I keep coming back to is a lot of these questions, there’s really no binary answers. And I think everyone now lives in the world of complexity that immunologists and infectious disease scientists have been existing in. What I mean by this is when you ask me if there is an immune response to Vaccine A against Viral Variance B and I can tell you, well, it seems to be 50 to 70% reduced in this one study in this one population, and that’s the best data we have right now; ask again in two months after more studies have come in — we all share this appreciation for scientific complexity and the evolution of our knowledge and also that some questions have a spectrum of answers rather than a yes or no. So thank you for that.

[0:28:33]

RICK WEISS: Yeah, very interesting. And it doesn’t lend itself to easy journalism when you have to sort of describe the spectrum instead of getting it down to six words in your lead. But great advice. Thank you. Christian?

[0:28:46]

CHRISTIAN SANDROCK: Yeah. I think, you know, one of the big things that we’re sort of dealing with is a lot around vaccinations. So you know, now we’re a few months into the rollout of the vaccines. We started with health care workers. And, you know, I think it’s really, really probably the most interesting that, particularly with health care workers, you have a lot of people who don’t want the vaccine. And what I haven’t really seen in the media is a discussion of the side effects and the adverse events of the vaccine in relation to the long-term effects of COVID. So you know, one of the — and you know, Dr. Akselrod probably had the same issues. You know, I’d walk down the hallway in my hospital, and people would say, well, tell me about the Pfizer vaccine. Tell me about the Moderna vaccine. What are the side effects? You know, do we know anything long-term about these mRNA vaccines? And the answer is, sure, this is cutting — more cutting-edge technology. This — you know, these vaccines were approved on the EUA basis. We’re rolling them out.

But the most interesting thing is we know now there are long-term effects from COVID. And you know, as a person and as a scientist and as a physician and as a parent, if I had to choose between a vaccine and, you know, knowing pretty much that all the vaccines we have don’t have really long-term effects versus the long-term effects we’re seeing with COVID, I would always choose the vaccine. And I’m very surprised that many of our patients and many of the public are still really that hesitant about vaccines. And I know — we know this existed long before with the measles vaccines and the multiple outbreaks we saw prior to COVID. And I’m hoping that at least this pandemic will give us a nice chance to really talk about vaccines, the value of vaccines, and how they’re one of the better — you know, really one of the most amazing public health interventions we’ve had. And I think that’s — you know, the balance of, you know, the risk of a long-term disease and the risk of the vaccine is what we do in public health and medicine all the time. And it’s nice to see that. And I would like to see that discussion more happen on a regular basis. And the second is I want to echo something Dr. Akselrod said, which is really the uncertainty of what we do every day.

So, you know, if I — I like to cook a lot, so if I liken this to cooking, you know, it’s almost like we follow a recipe with a lot of the patients we manage on a daily basis. Not only do we not have a recipe; I’m cooking with ingredients I’ve never seen before. And while that’s intellectually stimulating, it’s hard. So we learn things, and things change all the time, and how I might cook or prepare a particular ingredient changes as I work with it. And that’s what we’re seeing in the scientific community. So if someone gets upset that, well, the CDC said no masks in the beginning, and now they’re telling us we need to double-mask, that’s because science evolves. And that’s science. And that’s what we sort of have, and we need to accept that things are going to change. And we’re going to make the best decisions with the data we have at the time and that the public has to accept that things are not black and white, as Dr. Akselrod said — that it’s really fluid, and it’s going to change, and those recommendations are going to change and that science is not fake with those changes. So anyway, with that, I’ll stop.

[0:31:35]

RICK WEISS: Great reminder, and it’s good news for us that it’s not just the virus that’s evolving, but the science is too. Let’s hope the second, you know, keeps up or overtakes the first. OK. I want to move into some questions from the reporters online. I’m going to start with one from Zachary Orlins at ABC News Medical Unit, although I think Kent Jackson at the Standard-Speaker in Hazleton had something similar, so you’ll serve them and others. The question is, what do you think of efforts to create a universal COVID-19 vaccine that would work against all the new variants? We know that there are some mutations or some areas of the virus that may not be prone to mutation and maybe would be good targets for what would be a universal vaccine. How far away is this? How practical is it? Are there people working on it, and is it close? And I don’t know which one of you might be closer to that. Hana, you were addressing variants. Do you want to start with anything about the possibilities for this?

[0:32:32]

HANA AKSELROD: Absolutely. So thank you for that. That indeed is the holy grail — a panvariant vaccine that will be effective against the conserved portion of the virus. And that has been a target of many, many years and decades of investigation in the flu vaccine world. The National Institutes of Health has supported the search for a universal flu vaccine for a very long time and for an HIV vaccine, also, to name another virus with the ability to mutate quite rapidly. Those will take a long time, in part because — it was faster to develop a vaccine targeting the spike protein, in part because of work that was done on this starting 17 years ago when the first SARS virus emerged, caused thousands of cases and hundreds of deaths and then was wrestled under control using strict epidemiologic and public health measures. So a lot of the vaccine research we’ve been capitalizing on in the fight against SARS-CoV-2 was started in the days of the original SARS. And the spike protein sitting directly on the surface and being the part that most directly interacts with human receptors was a natural area to target. There are parts of the virus that, as you say, mutate less quickly.

But there is less known about how immunity to those epitopes or those targets arises, and it will probably take a longer time to get there. In the meantime, we can use the vaccine research done so far and the fact that the virus is changing a little bit of the time. Those are tiny molecular changes in the shape of its surface on the spike. Even if we don’t preserve 100% of the binding between the antibody and the spike, if we don’t preserve 100% of the immunity people get from prior infection or immunization, there may be enough cross-reactivity to at least slow down the virus and how much it replicates or help the immune system kick in and mount its defenses and clear the virus out of the body before it has time to do extensive damage, cause severe or critical disease, and have someone become Dr. Sandrock’s patient in the ICU. So even if the vaccine is partially effective, so to speak, if it prevents mild and moderate disease, that’s the holy grail. If it prevents critical illness but allows some people to still have symptoms, you know, we might still count that a win in the big scheme of things.

[0:35:36]

RICK WEISS: Great, thank you. Christian, did you want to add anything to that in terms of the time schedule or…

[0:35:43]

CHRISTIAN SANDROCK: No. I think what Dr. Akselrod said about reducing the symptoms and severity is key. And next week, we’re going to see the J&J vaccine’s going to — I think it’s next week — go in front of the FDA. We’ll get a lot more indication on that data and how it prevents, you know, moderate to severe cases of COVID, and I think that’s really the key. And, you know, the push from our end is to say, yeah, there might be new variants, and if the B.1.1.7 variant is becoming predominant in the U.S., that doesn’t mean you don’t get vaccinated with the current vaccine. It really might reduce the severity of the illness you have. It may not prevent you from getting it, but by reducing severity, you know, you may be less transmissible, and you may not end up in our ICU. And I think that’s the key point, and Dr. Akselrod said it perfectly.

[0:36:25]

RICK WEISS: Not letting the perfect get in the way of the good, sounds like to me. Question here from Carol Thompson at the Lansing State Journal in Michigan — some question about the tracking spread of the variants. Who is doing the sequencing in the United States? Are we doing enough sequencing in this country to track these variants and know what’s happening? And what is a good resource for reporters to learn who is conducting the sequencing locally? Hana, I’ll start with you again here.

[0:36:54]

HANA AKSELROD: Terrific questions. So not every lab that can test for COVID-19 has the capacity to do viral sequencing. Those are typically public health labs or university research labs or pharmaceutical and commercial research labs that have that kind of equipment and trained personnel. That said, we may see tests come out in the coming weeks and months and come in front of the FDA to make testing for variants more accessible. Now, in the meantime, your best resource is your Department of Public Health because where they send their samples for sequencing will vary depending on where you are. The CDC has the database tracking of viral variants and the available resources on them. So I have a slide of references that I hope will be shared at the end of the talks that basically shows the genomic surveillance database and dashboard for the United States.

There are more research-oriented resources, such as the global Nextstrain database, which are more of interest to research scientists. In terms of do we have the capacity, we don’t. We, frankly, have had an underpowered public health system for years to decades heading into this. And this is part of why we were, relatively speaking, behind the virus and why it got so many steps ahead of us last spring. So we now know where our deficiencies lie, and we are an actively learning species. As Dr. Sandrock said, it’s — or as Rick said, it’s not just the virus that is evolving; it’s our response to it too. One of the great areas of learning for the past year has been that we need a lot of new public health students, microbiology students and medical students to deal with what we’re seeing.

[0:39:04]

RICK WEISS: Thank you. Dr. Sandrock, there’s a question here directed to you from Anne Conner, a freelancer in Vermont. She says she’s heard that some COVID-19 patients suffer from “COVID toes” and tooth loss months after they have recovered from acute COVID. How common are these symptoms?

[0:39:25]

CHRISTIAN SANDROCK: Yeah, that’s a great question. And we are seeing that COVID-related skin disease is really relatively common. About half of the people that have a post-acute COVID syndrome are going to have some different skin abnormalities. That includes hair loss and teeth loss within that. What specifically is going to be the classic COVID toes or what specifically is going to be tooth loss is a little bit less known. That probably all relates, again, to that microvascular disease we talked about where there’s limited flow plus chronic illness. So you can imagine, if you have a real chronic illness, hair loss and tooth loss — which we see, for example, in autoimmune diseases like lupus and rheumatoid arthritis — can happen as well. So, you know, what is driving that is a little bit unknown, but there’s probably some microvascular disease and autoimmune component. How common specifically is COVID toes or tooth loss? I don’t have exact numbers on that.

Now, COVID toes is — if you’ve seen a picture, if you Google it online, you’ll sort of have these purple-pinkish toes, and that actually is a beautiful example of microvascular thrombosis. So that’s — at the real capillary level in those distal toes, you have limited blood flow. Imagine that happening in your heart, your brain, your lungs. That’s what we see. It drives a lot of the severe symptoms in COVID. And normally, we see COVID toes in the acute phase, but there are some long-term effects, as those tissues die, that you’ll actually have loss of your skin, loss of some of the muscle, even loss of your toes that come with it down the road, so that is part of the process, absolutely. I don’t — I’m sorry I don’t have exact numbers. I think that’s still evolving. But just know that skin lesions, hair loss, and tooth loss make up at least half of what we see. But specifically, those things are — I don’t have exact numbers on those.

[0:41:07]

RICK WEISS: Well, if those descriptions don’t get a few more people to get vaccinated, I don’t know what will. Thank you for that answer. Here’s a question from Veronica Marshall, WINK-TV in Fort Myers. I’d love to hear the experts talk about how T cells could help us in our immunization push now that variants are rendering our current antibody vaccines less effective. What is the role of T cells there, and how might that help? Hana, can you take that for starters?

[0:41:37]

HANA AKSELROD: Sure. So when we’re talking about our immune response, it’s not purely based on antibodies. Our adaptive immune system includes both the B cells that provide or manufacture antibodies and the T cells, which have a greater function in interacting with the pathogen, interacting with infectious — infected cells and signaling to the B cells that they need to take action and kick up production. And there are aspects of the immune response that persist even after antibody levels settle down or fade away, at least as far as we can tell from research studies done in the past year. This seems to be part of what our immune system does after infection with SARS-CoV-2.

There is a research group at La Jolla Institute in California that’s been doing a lot of very cutting-edge work on this. And another institution where a lot of the research is happening is Mount Sinai School of Medicine in New York. So what researchers have been looking at is responses in the B cells, T cells and antibody levels after natural infection and now also after immunization. And there are reasons to believe that the B and T cell responses or changes persist for much longer and have a slower decline compared to just the drop-off in antibody levels. Now, that’s for the antibody levels, not antibody shapes. When we’re talking about different variants, you might get a slightly different shape of antibody that was produced before that’s no longer 100% a match for that three-dimensional binding site. But will the T cells still be able to recognize the pathogen, even partially? So there is, on the immunology research level, cautious optimism that we will get enough of cross-reacting recognition from T cells over time to kind of build up our memory bank against this virus.

The question that remains to be answered is, will this require repeat exposures to different versions of the virus — or, ideally, different versions of the vaccine rather than the whole virus to avoid the actual symptoms of getting ill. And we will see. I believe it depends on what the virus does and what we do. It’s starting to feel like we’re in a game of chess with this virus. Like, we made the vaccine. Your move, virus. Well, it created some new variants that can get around the vaccine. We will probably keep playing. We’re in the midgame now. And our overall goal is to drive the population of the virus down so that there’s less of it out there with fewer opportunities to mutate and create newer variants. In the long run, I believe that the combination of our immune system memory and our response as a learning species and our behavior changes will help us bring the epidemic under control and make this virus something we can live with, not die from and boost against every once in a while.

[0:45:04]

RICK WEISS: Great answer, thank you. Dr. Sandrock, question for you from Anna Noagrovsky (ph). She’s a freelancer in Massachusetts. Do we know if asymptomatic COVID cases ever get post-COVID syndrome?

[0:45:20]

CHRISTIAN SANDROCK: You know, great question, and we don’t. Most of the people who have persistent symptoms after their acute phase of COVID really had an acute phase, right? So if you’re truly an asymptomatic patient where you come in, the virus infects, replicates and then disappears — many of those patients actually don’t know it, and they have not really presented. Now, that doesn’t mean we might not find out down the road that that’s the case. But right now, it appears that you at least have to have, as part of that process, an acute phase that has some symptoms — again, very variable how severe and what level, but that there’s some symptoms involved. So — but we may find out down the road that usually with, you know, asymptomatic patients, there may be some lingering effects. But right now, usually, again, the things — just microvascular disease, the — you know, the large inflammatory response — usually comes with some level of symptoms up front that then drive that later in the disease.

[0:46:13]

RICK WEISS: OK. I’ve got a question next from Sabrina Wilson at FOX 8 in New Orleans, and this really follows on, I think, one of the last things you were just talking about, Hana — about the race between getting people vaccinated and the variant production by the virus. She asks, are you concerned that the current pace that vaccines are being administered in the United States will give the variants time to take hold in this country? Can you talk about that dynamic a little bit?

[0:46:48]

HANA AKSELROD: Yes. So right now, the emerging variants are not dominant anywhere in the U.S. We don’t have the situation that South Africa has, for instance, where the B.1.351 has become dominant to the point that it’s getting in the way of their plans to vaccinate with the AstraZeneca vaccine, to which it is less susceptible — or what we’ve seen in the U.K. over the fall into winter period, when they were previously controlling the spread of COVID-19 using public health measures, school closures, social distancing, and then the new 50-70% more transmissible variant, B.1.1.7, came up and started to spread despite some of these measures, and they had to be more strict about their isolation, distancing and so on. So where we are in the U.S. is we’re — fortunately, we’re seeing a big decrease in cases over the past months. We think it is because the holidays are behind us but also because we’ve learned what not to do. There’s still a lot of what we call wild-type virus circulating out there, and there are locally emerging variants within the U.S.

You may see reports about a variant in California or in other states now that we are paying more attention and diverting more of our resources to testing for those variants. We may learn that some of them have been spreading longer than we know. Where this leaves us with regards to our vaccine drives is — well, it makes it so much more urgent to get as many people vaccinated with the vaccines while they’re still maximally effective before we give the new variants time to take hold. Essentially, some protection is better than no protection when it comes to someone’s odds of becoming infected with the new variant, so why not use all the means in our disposal at once to really not just flatten but crush the curve of transmission? And let’s never find out how big of a foothold B.1.1.7, P.1, et cetera, can have here.

[0:49:11]

RICK WEISS: Great, thank you. Dr. Sandrock, I’m going to give you a pair of questions here — two parts. The first is from Jeanne Pinder at Clear Health Costs, and it — who asks, what would cause the persistent joint and muscle aches and pains that we’ve heard about in post-acute COVID patients? Is that also probably microvascular or something more having to do with inflammation? So a joint and muscle aches question there — and then from Andrea Kane at CNN, can you provide any suggestions for clearinghouses, for studies on post-COVID syndrome or a place where reporters can go to keep up on guidelines? Is the CDC doing that? Or where is the best place for reporters to keep track of what’s going on with this disease?

[0:50:01]

CHRISTIAN SANDROCK: Great — so both great questions, and I wish I had perfect answers, but I may not. The first, with — dealing with the joint pain, you know, usually, that is interesting. It’s probably not — and I’m going to say probably because I don’t have clear data or biopsy data, but it’s probably not associated with microvascular disease like we would see in the lung, GI tract, heart or brain. And it’s more a byproduct of just systemic inflammation but may be a byproduct as well as autoimmune disease. So you can imagine, when you get influenza or even acute COVID, having body aches, joint aches, muscle aches is very common. The persistence of that could be — and as it changes and focuses on specific joints like the shoulder, knee, you know, different hand and wrist joints, that’s probably more of an autoimmune process that’s focusing in on the synovium or the — you know, the lining of those joints and causing inflammation. The muscles could be systemic inflammation.

That actually could be some microvascular disease in the muscle bit. So it’s — that’s the part that’s really hard to say, is, is it one thing tying it all together or, like, different pathologic processes, which then gets to the next question, which is what clearinghouse do we have, and where is a good place to go for all of this research and data and cutting-edge technologies? And as far as I know, unless some of you know and unless Dr. Akselrod knows, I don’t know of any. I do know that, you know, you can look — that the NIH has an RFA out where they’re going to actually study outcomes in cohorts, in groups of patients, ideally where these groups are going to be looked at over multiple sites. That’s No. 1. And then No. 2 is, you know, to develop a data consortium where we may be able to collect these patients across multiple academic centers and look at the data. And that’s going to be — probably be the best place.

Now, public health — as far as I know, there’s no local, state or, you know, the federal. The CDC — they do not require reporting, and there’s no tracking of this. So most of the data, when we look at the incidence of acute post-COVID syndrome, is all based on current studies — one which I mentioned, but quite a few other ones that are out there. But as far as I know, no one’s really collecting this data. But the NIH is very eager to start funding those processes, and I think in the near future, we’ll have some data. There is one group, a smaller grant out of UCSF, that is looking at, you know, following these people up, similar to what’s been done in Michigan and, you know, in China and Europe, as well, to get some sort of data. But that’s about the best we have, is just these smaller cohorts that have been published. And unfortunately, we don’t really have anything bigger at the moment which shows the need for it.

[0:52:30]

RICK WEISS: OK.

[0:52:32]

HANA AKSELROD: Yeah. To follow on that, Dr. Sandrock, I agree. Our institution also has a post-COVID care clinic now, and we have been informally coordinating with two or three other clinics in different parts of the country, trying to standardize our data collection. I think a lot of programs are starting to see the need to build geographically, ethnically, et cetera, diverse cohorts to study how this syndrome affects different populations. What gets in the way a little bit is we have to balance taking care of acutely ill people with COVID with all of the follow-up care in a health care system that’s already straining at the seams. So hopefully, the release of research funding from the NIH and the increased visibility of patients still suffering from prolonged symptoms after COVID — hopefully all of that will help us gain momentum and find the resources and the ability to do this important research.

[0:53:39]

CHRISTIAN SANDROCK: Yeah, we — you know, we have the same clinic. And interestingly enough, on Fridays, across all of the UCs, we actually get on the — we have a call, a Zoom meeting like this, where we actually just sit in and talk about what we’re doing. So it’s, you know, very interesting what Dr. Akselrod brought up. And we’ll say, hey, I tried anticoagulation, and I noticed this group of patients gets better. Now, that’s far from science. That’s purely anecdotal, but it gives us some sense of where we may go. And I know in our clinic, you know, we have about nine disciplines in our post-COVID clinic because if you come in and, you know, loss of smell is all you have, we may have our ENT doctor see you. If you come in with depression and, you know, neurocognitive deficits, that’s more neurology and psychiatry. Shortness of breath and low oxygen levels — you’re going to visit me. So, you know, we’re doing exactly what they’re doing at GW. So very much those trends across academic centers need to be coordinated, and I’m hopeful with NIH, you know, ROA that’s coming out. So we’ll see.

[0:54:34]

RICK WEISS: Sounds like reporters for now need to be staying in touch with individual research institutions and try to track those stories locally and at that scale until we get a more central set of knowledge together. This is what happens, I guess, when reporters are covering something in real time that is so early in its evolution. We’re just about out of time, and I really want to ask each of you for a wrap-up point. But before I turn it over to you for a last question this way, I want to remind everyone on the line that all these slides and transcript will be up in the next day or two so you can study them more closely and get transcripts. I also want to encourage all of you — when you log off today, you will see a prompt for a very short three-question survey. It’s very helpful to us. If you appreciate these briefings at all or if you don’t, please take the half a minute to answer that survey and let us know what you think about how the briefings are going. With that, I want to turn to each of you and ask you to just sort of wrap up with some kind of a take-home message — maybe it’s something you’ve already said; maybe it’s something new, that if there’s one thing you want reporters today to walk away with — a thought, an idea — what would that be? And Dr. Akselrod, I’ll start with you.

[0:55:46]

HANA AKSELROD: Well, thank you so much for this opportunity, and thank you for everyone’s attention to the minutia of SARS-CoV-2 virology. To me, the takeaway message from this conversation today is really that we’re dealing with overlapping issues — the risk of a severe disease with long-term consequences for far too many people, the risk of letting virus spread uncontrolled to the point where it is fated to develop new variants because we’ve given it room to spread and experiment, and the need for us to stay on our toes and to continue to learn from both of these situations, both from the virus and what it does and the humans that are affected by it and what their needs are in the long run. It really reinforces for me the importance of learning institutions, both in the traditional sense of academic institutions and research but also in creating and building a public health system and a public support structure that’s capable of adaptation and responding to a change in pandemic. So thank you for helping us communicate about it and helping us think through it.

[0:57:07]

RICK WEISS: Fantastic. Thank you. Dr. Sandrock.

[0:57:10]

CHRISTIAN SANDROCK: Yeah, I would — certainly, I probably am going to be akin to what Dr. Akselrod said. And I think, you know, science is not perfect, but it’s far and away the best we have. And as we as a society have evolved to have social media and other different avenues of news media and as such, there’s a lot of false information. Really, that’s been one of our bigger battles. And I would have to say, you know, when I worked on pandemics in the past, I would have never expected the amount of information and social media campaigns that have come forward that have made our job significantly harder.

So I think the take-home point is that, you know, science isn’t perfect. It’s the best we have. We also have history to know that science has taken us this far. We have history of prior pandemics. We have the history, as Dr. Akselrod pointed, of this pandemic, and we have to use that to our advantage. And otherwise, if we don’t, those are great failings. Despite how great our vaccines are and how wonderful our medications, research and databases are, if we’re not going to do the basics, we’re really in trouble. So hopefully, we can learn from our lessons and really grow, which is hard to do but important.

[0:58:16]

RICK WEISS: Fantastic. Thank you both for those closing bits of advice and for everything you’ve offered today. I think this has been a particularly clear and educational briefing today, and I really appreciate it so much, you taking the time with us. Again, to the reporters on the line, thank you for attending. Please do fill out the survey at the end. Follow us on social media at @RealSciLine. Check out our website, sciline.org. And thank you. We’ll look forward to seeing you at our next media briefing. And do get in touch with us. If any of you need an expert on deadline or otherwise, we are ready to help you get more science into your stories. See you next time, and thanks again.