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

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.

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

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

This is Jenny Levine. She's a postdoctoral epidemiologist and infectious disease researcher at Emory University.

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

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.

Adults alive today were exposed to all of those for the first time in childhood. And 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.

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.

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.

Russian flu caused fever and fatigue and killed an estimated 1 million people.

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 just causes the common cold. So that could be a possible future for SARS-CoV-2.

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 Jenny think that even with vaccines, COVID is is here to stay.

I don't think that herd immunity is actually, in the long run, a possibility for SARS-CoV-2. But that 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 coexist in a much milder, more benign way.

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, at least in the short term, because there are still many, many people worldwide who have never had SARS coronavirus 2 and are still susceptible to it.

The factors that will shape SARS-CoV-2 in the post-pandemic world: reinfection, the seasonality of the virus, and the vaccine that's out there.

And how new variants of the coronavirus could upend everything we know about COVID If infections in young children become severe, then we need to rethink things. 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.

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 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.

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.

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 coronavirus 2 and are still susceptible to it.

Before we get too much further, there's a word Angela used that we should define. What does it mean to eliminate a virus?

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

Eradication is a very high bar.

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, are smallpox and rinderpest, which is an agricultural pathogen.

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

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.

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.

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.

One of the reasons why it's so hard to achieve sterilizing immunity is because of where viruses live.

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.

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.

But 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.

Angela says that while sterilizing immunity would be great, it's not necessary for an effective vaccine.

A vaccine that prevents severe disease, period, is going to be massively beneficial to public health. You know, 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.

Another hurdle to herd immunity is that we just don't have enough vaccines for everyone.

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.

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. Jenny believes the best we can hope for is transient herd immunity.

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 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.

I think that that's why we really need to focus once we get vaccines distributed in the US, 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.

So if reaching herd immunity isn't likely, what does that mean for SARS-CoV-2? We'll find out after the break. If SARS-CoV-2 can't be eliminated through herd immunity, it'll become endemic.

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.

This is Jeffrey Shaman. He's a professor of environmental health sciences at Columbia University's Mailman School of Public Health.

So an example of a virus that came over and spread in kind of epidemic fashion and then became endemic would be West Nile virus. That emerged in New York City in 1999. Within 5 years, it had spread across the entire continental United States and all of North America, for that matter. And it is now endemic.

At this recording, we're still in the pandemic phase of COVID and we still don't know what the next phase of SARS-CoV-2 will look like.

Are there gonna be areas of the world where they're just seeing it all the time? Are there gonna be areas of the world where it's gonna be this seasonal virus where it's gonna appear every year, some people are gonna get infected with it?

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.

90% of people have antibodies against each of these 4 different endemic coronaviruses that we already deal with and that cause the common cold.

90%. That means that just about everyone has had one of these common coronaviruses at some time. One of those 4 common coronaviruses is OC43. Possibly a descendant of the Russian flu. Before the COVID pandemic, Jeffrey and other researchers looked at how often people were getting infections with these other coronaviruses.

So we were seeing people being reinfected within the span of a year, and we even had 3 individuals who seemed to have 3 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 OC43 and HKU1, there is a lot of repeat infection.

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

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.

But repeat infections may not necessarily be a bad thing.

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.

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.

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 preexisting immunity. So that seems like one reasonably likely scenario, but it really— it depends on the infection fatality ratio staying low in young children.

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.

I feel like we need to be paying a lot of attention to this. The variant 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.

Variants like the one Jenny 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 reinfection with a new variant produces a milder infection, like it might with OC43, or if it could make someone sicker. Here's Jeffrey Shaman again.

There are viruses that cause more severe infections upon reinfection. This has been documented certainly in dengue, and we can see it in respiratory syncytial virus in some instances as well.

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 2 dozen participants, found 9 people with worse symptoms when they were infected with a new variant after their first infection.

So what we're seeing is a range of reactions here. And unfortunately, time is going 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.

Jenny agrees.

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 long-term implications, or a variant that can cause severe disease upon reinfection. Which is a scarier scenario and one that I think we need to really be on top of measuring.

Angela Rasmussen again.

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

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.

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

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's genetic material is structured. It can mutate way faster than coronaviruses.

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.

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.

Coronaviruses can't do that. They can recombine if there is a co-infection, and that does happen sometimes. But they don't have the ability to reassort like flu does.

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

So I think that once we manage to control transmission on a global scale, especially, we really won't see that much more of SARS coronavirus 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. We don't need to do annual boosters the way we do for influenza.

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. Epidemic is brought to you by Just Human Productions, or funded in part by listeners like you, or powered and distributed by Simplecast. Today's episode was produced by Zach Dyer and me. Our music is by The Blue Dot Sessions. Our production and research associate is Temitayo Fegbenle. Our interns are Annabel Chen, Brian Chen, and Sophie Varma. If you enjoy the show, please tell a friend about it today. And if you haven't already done so, leave us a review on Apple Podcasts. It helps more people find out about the show. Follow Epidemic on Twitter and Just Human Productions on Instagram. To learn more about the characters and big ideas you hear on the podcast. We love providing this and our other podcasts to the public for free, but producing a podcast costs money, and we've got to pay our staff. So please make a donation to help us keep this going. Just Human Productions is a 501(c)(3) nonprofit organization, so your donations to support our podcasts are tax deductible. Go to justhumanproductions.org/donate. /donate to make a donation. That's justhumanproductions.org/donate. And if you like the storytelling you hear on Epidemic, check out our sister podcast, American Diagnosis. On American Diagnosis, we cover some of the biggest public health challenges affecting the nation today. Past seasons covered topics like youth and mental health, the opioid overdose crisis, and gun violence in America. I'm Dr. Saleen Gounder. Thanks for listening to Epidemic.