S1E71: Is SARS-CoV-2 Here to Stay? / Jennie Lavine, Angela Rasmussen, Jeffrey Shaman

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“I don’t think that herd immunity is a possibility for SARS-CoV-2. I think there’s going to be a different kind of equilibrium that we reach in the future where humans and SARS-CoV-2 co-exist in a much milder, more benign way.” -Jennie Lavine

The end of the pandemic might not mean the end of SARS-CoV-2. In fact, many scientists think COVID is here to stay, even with vaccines. In this episode we’ll hear why we may never reach herd immunity, how the coronavirus could change over time, and why kids are the key to reducing the severity of the disease.

This podcast was created by Just Human Productions. We’re powered and distributed by Simplecast. We’re supported, in part, by listeners like you.

Jeffrey Shaman: I think if I had to put money on it, I think it’s more likely that this virus will be persisting in human populations for as long as I’m alive.

Jennie Lavine: I think there’s going to be a different kind of equilibrium that we reach in the future where humans and SARS-CoV-2 coexist in a much milder, more benign way.

Céline Gounder: You’re listening to EPIDEMIC, the podcast about the science, public health, and social impacts of the coronavirus pandemic. I’m your host, Dr. Céline Gounder. We’re going to start today’s show talking about a coronavirus. No, not SARS-CoV-2. Another one — OC43.

Jennie Lavine: Oh, yeah, OC43. This is a fun little science mystery.

Céline Gounder: This is Jennie Lavine. She’s a postdoctoral epidemiologist and infectious disease researcher at Emory University.

Jennie Lavine: So OC43 is one of the, the four circulating endemic coronaviruses. As far as we know, everybody has gotten it probably multiple times.

Céline Gounder: OC43 is very mild. Most people experience it like the common cold. Besides rare outbreaks in places like nursing homes, it’s not a cause of concern. But it might not have always been that way.

Jennie Lavine: Adults alive today were exposed to all of those for the first time in childhood. So it is possible that any of those, when they first entered the human population, could have caused a scenario, a pandemic, similar to what we’re seeing right now with SARS-CoV-2.

Céline Gounder: After the SARS outbreak in 2003, researchers started getting more interested in these less severe coronaviruses. They wanted to know when these milder coronaviruses first started infecting people.

Jennie Lavine: And the best guess was the late 1800s, which coincides with a time at which something that in newspapers and such, was called the Russian flu.

Céline Gounder: Russian flu caused fever and fatigue, and killed an estimated 1 million people.

Jennie Lavine: And so there’s a hypothesis that perhaps that Russian flu pandemic was actually an OC43 pandemic. And that was the emergence of OC43, which as time has passed now is just causes the common cold. So that could be a possible future for SARS-CoV-2.

Céline Gounder: Earlier this week when this episode was released, April 19th, marked another milestone in the pandemic. Vaccines became available to anyone over the age of 16 in the United States. Vaccinating as many people as possible is a key step to ending the pandemic. But an end to the pandemic might not mean the end of SARS-CoV-2. In fact, many scientists like me and Jennie think that even with vaccines, COVID is here to stay.

Jennie Lavine: I don’t think that herd immunity is actually, in the long run, a possibility for SARS-CoV-2. So I do not think that herd immunity is the goal, but that I do want to make it clear it doesn’t suggest that we’re going to live in this kind of pandemic state long into the future. I think there’s going to be a different kind of equilibrium that we reach in the future where humans and SARS-CoV-2 co-exist in a much milder, more benign way.

Céline Gounder: In this episode, we’re going to look at how SARS-CoV-2 could go from a pandemic to an endemic virus, like OC43. We’ll learn why we may never reach herd immunity with SARS-CoV-2…

Angela Rasmussen: At least in the short term. Um, because there are still many, many people worldwide who have never had SARS-CoV-2 and are still susceptible to it.

Céline Gounder: The factors that will shape SARS-CoV-2 in a post-pandemic world…

Jeffery Shaman: So you have those three factors: re-infection, the seasonality of the virus, and the vaccine

Céline Gounder: And how new variants of the coronavirus could upend everything we know about COVID.

Jennie Lavine: If infections in young children become severe, then we need to rethink things.

Céline Gounder: Today on EPIDEMIC, SARS-CoV-2 as an endemic virus.

Ever since the beginning of the pandemic, there’s one phrase we’ve heard over and over again — herd immunity. That’s when there are so many people in the population who are immune to a virus, even if it does infect someone, it has nowhere left to go.

Jennie Lavine: So it’s kind of like if you were trying to make a fire and most of the sticks were wet, you wouldn’t be able to start the fire. Even if you put a lot of sparks in there. Uh, because there’s not enough dry wood. And when you put in a lot of people that have immunity, it’s like adding a lot of wet wood and it’s very hard to start the fire.

Céline Gounder: But Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan, thinks there’s still a lot of fuel left for this pandemic.

Angela Rasmussen: So I think that it’s pretty unlikely that we’re going to eliminate it at least in the short term. Because there are still many, many people worldwide who have never had SARS-CoV-2 and are still susceptible to it.

Céline Gounder: Before we get too much farther, there’s a word Angela used that we should define. What does it mean to eliminate a virus?

Angela Rasmussen: Elimination just means that you are, um, eliminating that virus from circulation within a given population. And that’s different from eradication, which basically means you wipe it off the face of the earth and stop it from circulating in any human population or animal population.

Céline Gounder: Eradication is a very high bar.

Angela Rasmussen: We haven’t successfully eradicated very many viruses at all. In fact, the only two viruses that we’ve managed to eradicate at least in nature, um, are smallpox and rinderpest, which is an agricultural pathogen.

Céline Gounder: Every virus has a different threshold for herd immunity. We still don’t know for sure what that is for SARS-CoV-2, but it’s likely very high — perhaps even over 80%.

Jennie Lavine: However, there’s a bunch of sort of caveats to this. One of them is that when we think about generating immunity, so how do we get to that herd immunity threshold? The herd immunity threshold depends entirely on transmission blocking immunity.

Céline Gounder: All the vaccines available in the United States right now offer protection from severe disease. But more research is needed to know how well they’ll prevent the spread of the virus. That’s called sterilizing immunity.

Jennie Lavine: So it’s like the strongest, strongest, strongest version of immunity. So if I had sterilizing immunity against SARS-CoV-2, it would mean that you could take a dropper full of, liquid and viral particles and put it up my nose, and my immune system would be so good at fighting that off that I wouldn’t get infected, the virus wouldn’t be able to replicate in me. I wouldn’t get sick and I wouldn’t transmit it.

Céline Gounder: One of the reasons why it’s so hard to achieve sterilizing immunity is because of where viruses live.

Angela Rasmussen: It’s very difficult to induce completely sterilizing protection via a mucosal surface, like the nose. That’s one of the reasons why the influenza vaccine is also thought to not be completely protective every year.

Céline Gounder: When you get a COVID vaccine shot, like an injection in your shoulder, it activates your immune system to release antibodies that try to fight off any SARS-CoV-2 virus it might find. Those antibodies are called IgG antibodies. But there’s another kind of antibody that lives in your nose and mucus. They’re called IgA antibodies.

Angela Rasmussen: That’s why people have been talking about switching to an intranasal vaccination that might be able to produce some of those mucosal specific immune responses for viruses that are acquired through that mucosal surface.

Céline Gounder: Angela says that while sterilizing immunity would be great, it’s not necessary for an effective vaccine.

Angela Rasmussen: A vaccine that prevents severe disease period is going to be massively beneficial to public health. We have a number of vaccines that are very effective and that have effectively eliminated viruses from populations like the inactivated polio vaccine, for example, that don’t produce completely sterilizing immunity.

Céline Gounder: Another hurdle to herd immunity is that we just don’t have enough vaccines for everyone.

Angela Rasmussen: I think the thing that, that’s really worrisome is the possibility that if vaccination and immunization takes a long time for the global population, that circulating virus will continue to mutate. New variants could emerge that are capable of getting around the vaccine-induced immunity and will then be able to cause severe disease again in people.

Céline Gounder: These are big challenges to herd immunity. Uneven access to vaccines, questions about how long immunity lasts, and a lot of people still susceptible to the virus. Jennie believes the best we can hope for is transient herd immunity.

Jennie Lavine: So if you can vaccinate really quickly in a population, you can get this kind of refractory period where there’s not enough susceptibles for a little while, but there’s going to start susceptibles will start building up as they lose their immunity, or they lose their transmission blocking immunity, or the virus evolves away and we get new variants that can escape that to some degree.

Angela Rasmussen: I think that that’s why we really need to focus once we get vaccines distributed in the U.S. Um, we need to focus on global immunization because the sooner we can get this under control globally, the sooner it’s not going to be a problem for anybody.

Céline Gounder: So if reaching herd immunity isn’t likely… What does that mean for SARS-CoV-2? We’ll find out after the break.

* * *

Céline Gounder: If SARS-CoV-2 can’t be eliminated through herd immunity… it’ll become endemic.

Jeffrey Shaman: An endemic pathogen is something that is just present in the community. I think in the strictest sense, it’s something that’s there all the time and constantly being transmitted.

Céline Gounder: This is Jeffrey Shaman. He’s a Professor of Environmental Health Sciences at Columbia University’s Mailman School of Public Health.

Jeffrey Shaman: So an example of a virus that came over and spread and kind of epidemic fashion, and then became endemic would be West Nile virus. That emerged in New York City in 1999. Within five years it had spread across the entire continental United States and all of North America for that matter. And it is now endemic.

Céline Gounder: At this recording, we are still in the pandemic phase of COVID, and we still don’t know what the next phase of SARS-CoV-2 will look like.

Jeffrey Shaman: Are there going to be areas of the world where they’re just seeing it all the time, or they’re going to be areas of the world where it’s going to be the seasonal virus, where it’s going to appear every year? Some people are going to get infected with it.

Céline Gounder: One of the most important questions scientists are trying to answer is how long will immunity last to SARS-CoV-2? Jeffrey and others are looking to common coronaviruses for clues about how SARS-CoV-2 might behave.

Jeffrey Shaman: 90% of people have antibodies against each of these four different endemic coronaviruses that we already deal with and that cause the common cold.

Céline Gounder: 90% — that means just about everyone has had one of these common coronaviruses at sometime. One of those four common coronaviruses is OC43, possibly a descendent of the Russian flu. Before the COVID pandemic, Jeffrey and other researchers looked at how often people were getting infections with these other coronaviruses.

Jeffrey Shaman: So we were seeing people being reinfected within the span of a year. And we even had three individuals who seem to have three infections with the same coronavirus within the span of a year. So our takeaway from this is that within the endemic coronaviruses, and certainly the endemic beta-coronaviruses, so OC43 and HKU1, there is a lot of repeat infection.

Céline Gounder: This suggests that natural immunity to common coronaviruses like OC43 may not last very long.

Jeffrey Shaman: Of course, this begs the question: is this something that’s going to happen with SARS-CoV-2? And the answer of course is: we don’t know.

Céline Gounder: But repeat infections may not necessarily be a bad thing.

Jennie Lavine: What we saw with other coronaviruses. And it’s, we’re seeing similar data now from SARS-CoV-2, is that getting a second infection, getting a reinfection is more mild than the first infection.

Céline Gounder: This is one way that people develop natural immunity to common coronaviruses like OC43. People get infected many times during their life with these common cold viruses, and subsequent infections are — generally speaking — milder.

Jennie Lavine:  And so in the future, what would happen is everyone would get infected for the first time as a young kid. It would be mild because they’re a kid and then they would get reinfected throughout life. And it would be mild because they had some pre-existing immunity. So that seems like one reasonably likely scenario. But it really, it depends on the infection, fatality ratio staying low in young children.

Céline Gounder: As devastating as COVID has been, one saving grace is that the disease has not posed a serious risk to most children. But as the virus continues to mutate… there’s no guarantee that will always be the case.

Jennie Lavine: I feel like we need to be paying a lot of attention to this. The variant that’s that’s spreading in India right now, there seems to be an increase in severe cases in young children. And that, that is of concern. And I think something that we need to be collecting data on ASAP.

Céline Gounder: Variants like the one Jennie mentioned in India could throw off this gradual easing of disease severity. We’ve already seen reinfections of coronavirus in places where new variants are circulating. But what’s unclear is if re-infection with a new variant produces a midler infection — like it might with OC43 — or if it could make someone sicker.

Céline Gounder: Here’s Jeffrey Shaman again.

Jeffrey Shaman: There are viruses that cause more severe infections upon re-infection. This has been documented certainly in dengue, and we can see it in a respiratory syncytial virus in some instances as well.

Céline Gounder: Jeffrey says it’s still very early to know for sure if this is the case with SARS-CoV-2. More data is needed. One small study — just two dozen participants — found nine people with worse symptoms when they were infected with a new variant after their first infection.

Jeffrey Shaman: So what we’re seeing is a range of reactions here. And unfortunately it’s going to be time to be the necessary ingredient for telling us whether people really are at risk of more severe complications when they’re repeatedly infected or if it gets less severe over time.

Céline Gounder: Jennie agrees.

Jennie Lavine:  As far as I know, we haven’t really seen a lot of that individual level data. And what that means is it could be explained either by a more severe strain that is causing severe primary infections, which isn’t great, but doesn’t have really scary and long-term implications. Or a variant that can cause severe disease upon re-infection, which is a scarier scenario. And one that I think we need to really be on top of measuring.

Céline Gounder: Angela Rasmussen again.

Angela Rasmussen: It’s sort of like a decades-long arms race between the immune system and the virus as it continues mutating. That I think is maybe a preview of what we could expect potentially with SARS-CoV-2. So if it’s always circulating at a low level and constantly acquiring these changes, it could come back every fall and winter.

Céline Gounder: Comparing SARS-CoV-2 to other coronaviruses has many wondering if COVID could become another cold-season disease, like the flu. But Angela doesn’t like that comparison.

Angela Rasmussen: Flu is a little different. Influenza crosses species all the time, and that allows it to acquire mutations very quickly.

Céline Gounder: This is a big reason why influenza comes back every year. It can travel in migratory birds, which is at least partly why it’s a seasonal disease. The other is the way the influenza virus’ genetic material is structured… it can mutate way faster than coronaviruses.

Angela Rasmussen: Basically if two influenza viruses infect the same animal at the same time, Those different segments can be reassorted together, essentially shuffled together like two decks of cards that results in new influenza viruses that have some components of each of the virus that originally infected the host and that can have really, really unpredictable effects on both pathogenicity and transmissibility.

Céline Gounder: The virus infects birds and pigs, too, and can swap chunks of its genetic material across subtypes. It’s the difference between what we scientists call genetic drift and genetic shift.

Angela Rasmussen: Basically if two influenza viruses infect the same animal at the same time, Those different segments can be reassorted together, essentially shuffled together like two decks of cards that results in new influenza viruses that have some components of each of the virus that originally infected the host. Coronaviruses can’t do that. They can recombine, uh, if there is a co-infection and that does happen sometimes, but they don’t have the ability to, to reassort like flu does

Céline Gounder: There are also fewer kinds of coronavirus out there compared to influenza.

Angela Rasmussen: So I think that once we managed to control transmission on a global scale, especially, we really won’t see that much more of SARS-CoV-2. There’s always the possibility of course, that we might need to get boosters, but I think it’s pretty unlikely once this is under control, that we’ll be needing to get annual boosters the way we do for influenza.

Céline Gounder: But getting coronavirus under control is still a big lift. At this recording, the United States is still seeing more than 70,000 new cases of COVID every day. Not to mention transmission in other countries right now, like India and Brazil. More coronavirus cases means more chances for new, more dangerous variants that could outsmart our vaccines. So, if you haven’t gotten vaccinated yet, please give it serious thought. And remember, vaccines work best in communities, not individuals. It’s why we’re still recommending everyone wear a mask… until most of us are vaccinated. We all need to do our part to make sure SARS-CoV-2 comes under control. The OC43 coronavirus may have gone from pandemic to common cold… but that took over 100 years. That’s time none of us have.


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I’m Dr. Celine Gounder. Thanks for listening to EPIDEMIC.


Angela Rasmussen Angela Rasmussen
Jeffrey Shaman Jeffrey Shaman
Jennie Lavine Jennie Lavine
Dr. Celine Gounder Dr. Celine Gounder