S1E66: Brazil’s P.1 Variant — the Limits of Herd Immunity / Felipe Naveca, Ester Sabino

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“This is an invisible war and if we don’t use our weapons we are not going to win it.” -Ester Sabino

In the fall of 2020, the Brazilian city of Manaus had the highest SARS CoV-2 infection rate in the world — possibly as high as 75 percent. Some speculated that with rates of infection this high, there would not be enough people left for the virus to infect. Had the city reached so-called natural herd immunity? For a few months cases started to drop but this winter things got worse than ever. We’ll hear what caused this devastating second wave in Manaus, why herd immunity from natural infection wasn’t protective, and why — even with vaccines — we can’t let our guard down.

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

Felipe Gomes Naveca: The health system, Manaus was collapsing. We had a very, very hard situation at the beginning of January.

Ester Sabino: I think it might happen in other places. I think we are just seeing the first ones.

Felipe Gomes Naveca: Science is, is the only thing that we can use against such a important enemy, like this virus.

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.

The pandemic has hit Brazil worse than most. After the United States, Brazil has the highest number of reported coronavirus cases in the Western Hemisphere. And the hardest hit city in Brazil… is Manaus.

News montage: It’s the capital of the state of Amazonas, and it has been an example of the failure Brazil has to cope with COVID-19.

Medical staff describe an overwhelming crisis. They lack protective gear and medical equipment. And intensive care units have run out of beds.

In Manaus, cemetery workers could not dig graves fast enough. 

Céline Gounder: Manaus is a city of 2 million in the middle of the Amazon rainforest. It sits at the confluence of the Amazon and Negro Rivers.

Felipe Gomes Naveca: Manaus is like an Island. Because we have the forest on the side and also a big river on the other side.

Céline Gounder: That’s Felipe Gomes Naveca (Na-vey-ka). The jungle is visible across the city. And you can hear the birds through the window of Felipe’s office.

Felipe Gomes Naveca: I don’t know, in English, but in Brazil we call it B—– – there are a lot of those birds nearby.

Céline Gounder: Felipe is a public health researcher and virologist in Manaus. He’s been studying the spread and impact of SARS-CoV-2 in Amazonas. That’s the Brazilian state where Manaus is located. During the first wave of the pandemic, Manaus was hit really hard. Some of the most dramatic images from that time were from the cemeteries. Fields of freshly plowed earth covered in crosses marking the graves of COVID victims. The virus claimed lives from all over the city.

Felipe Gomes Naveca: There are at least four people from my team lost a mother or an uncle or father.

Céline Gounder: Felipe was one of them, too.

Felipe Gomes Naveca: At the first wave, I lost my father due to COVID-19. So it was really, uh,  something really hard for me. I did his PCR, so I was really involved in the situation, but, my father was a great fan of my work. So I had to think about this, to move forward and continue doing my job.

Céline Gounder: The pandemic was so out of control, Felipe had to be back at work just two days after his father died.

Felipe Gomes Naveca: You don’t have time to cry for our relatives, and we have to return to the lab. So maybe when this pandemic is finished, we can rest and think better about this. We are really tired at this moment.

Céline Gounder: As devastating as this first wave was… by September some thought the worst had passed. But by December, the city was in crisis… again.

Felipe Gomes Naveca: We are facing our worst time in Brazil, even worse than last year. We have an increasing number of cases and even deaths in several Brazilian States. So we are facing a very hard time at this point.

Céline Gounder: There are a lot of parallels between Brazil’s experience with SARS-CoV-2 and that of the United States. Both countries took a hands-off approach to the virus at the beginning of the pandemic. Leaders in both countries pushed policies that let the virus rage… claiming it would lead to herd immunity. But that’s not what happened in Manaus.

In this episode, we’ll look at what went so wrong in Manaus… and what it could mean for the United States. We’ll hear what caused this devastating second wave in Manaus…

Ester Sabino: I’m very worried about these new variants.

Céline Gounder: Why herd immunity from natural infection wasn’t protective…

Felipe Gomes Naveca: The virus had the chance to evolve for too long. And that’s what we are seeing now.

Céline Gounder: And why — even with vaccines — we can’t let our guard down.

Ester Sabino: This is a war. It’s an invisible war. And if we don’t use our weapons, we are not going to win it.

Céline Gounder: Today on EPIDEMIC, Manaus and the limits of herd immunity. 

Ester Sabino is a researcher and physician in Sao Paulo. Before the pandemic, Ester was working with a team from Oxford University to improve Brazil’s ability to respond to outbreaks. She worked on viruses like HIV, dengue, and Zika.

Ester Sabino: And so all the idea was to get sequences from the virus quickly enough to give some information for the public health.

Céline Gounder: So when the coronavirus arrived in Brazil, Ester and her team shifted their attention.

Ester Sabino: We were responsible for sequencing the first case. So the first case arrived through a person traveling from Italy to Sao Paulo.

Céline Gounder: It was Carnaval. People from all over the world were coming to Brazil for the parties and parades. The virus spread to cities like Rio de Janeiro, Fortaleza, and Manaus. But Brazil’s President, Jair (Ja-ear) Bolsanaro, downplayed the risk. Like former-President Trump, Bolsonaro criticized masks. He refused to implement social distancing measures and other non-medical means to control the spread. Tracking the virus in those early months of the pandemic was a challenge. Testing wasn’t widely available. But Ester and her team had an idea: the blood banks.

Ester Sabino: In Brazil, the blood bank saved their samples. It’s mandatory to save for six months. So we were able to get a grant and start doing serological tests, since the beginning of the pandemic.

Céline Gounder: So Ester’s team got to work. They looked for traces of SARS-CoV-2 antibodies in donated blood. Using this data, they were able to estimate how much of the population had been infected. Sao Paulo and Manaus were the first cities Ester looked at. She estimated that around 30% of Sao Paulo had been infected by October 2020. But Manaus was worse. Much worse.

Ester Sabino: About 50% of the population had antibodies in June.

Céline Gounder: A study Ester co-authored estimated that 66% of Manaus had been infected by September.

Ester Sabino: And by making the corrections, probably 75% of the population had already been exposed to the virus by October.

Céline Gounder: 75%. These are dizzyingly high infection rates. For comparison, as of November, before the winter surge, about 20% of NYC’s population had been infected. Ester says they don’t know for sure why Manaus got hit so hard. But she has a guess:

Ester Sabino: The number of people per house in Manaus is higher than the number of people per house in Sao Paulo.

Céline Gounder: Data from cell phones showed that people were practicing similar levels of social distancing in both cities. But the number of people in a given home in Manaus was higher.

Ester Sabino: And maybe the, the way that the pandemic is transmitted is through inside the people’s house.

Céline Gounder: The infection rate was so high in Manaus, it sparked debate as to if the city might be the first place on the planet to reach so-called natural herd immunity. It’s important to remember that there’s no one magic number for herd immunity. The threshold for herd immunity is different for polio, for example, than measles. And at this point, we still don’t know what that figure is for SARS-CoV-2. But with infection rates possibly as high as 75%… and so, so many deaths… it appeared that Manaus had achieved it… at a very high price. And cases did start to fall. But that wouldn’t last. Cases started to climb again. Here’s Felipe Naveca (Na-vey-ka):

Felipe Gomes Naveca: It was really dramatic and in the middle of December. So there is, there is something that seems to be something new.

Céline Gounder: When the cases started to tick up, Felipe says they thought it could be a variant of concern, or VOC. They thought maybe it was one of the variants from South Africa or the United Kingdom.

Felipe Gomes Naveca: But to our surprise, it was a new VOC.

Céline Gounder: This new variant was discovered in Amazonas state in December 2020. Today, it’s known as P.1. We’ll hear where this new variant came from… and what it means for vaccines. That’s after the break.

***

Céline Gounder: Before the break, a new SARS-CoV-2 variant had been discovered in Manaus called P.1. Like P.1, the other variants of concern emerged in countries with high levels of coronavirus transmission, like the United Kingdom and South Africa. And here Manaus had the highest infection rates of anywhere in the world.

Felipe Gomes Naveca: We give the virus too much time to evolve and it evolves to a new variant. That seems to be more adapted to human beings.

Céline Gounder: We talked about this in previous episodes on variants of concern. The more the coronavirus spreads, the more opportunities it has to mutate. So areas with the worst outbreaks are likely to see more variants. The variant out of Brazil also demonstrates something called convergent evolution. That’s when something develops the same adaptations in different environments. P.1, for example, has many of the same adaptations as the B.1.351 variant found in South Africa. Both variants have similar mutations on the receptor binding domain — the part of the spike protein that attaches to human cells.

Ester Sabino: So it’s a combination of mutations that really help the virus to transmit more rapidly and to escape previous antibody responses.

Céline Gounder: Ester says this ability to evade previous antibody responses likely contributed to the surge of cases in Manaus this winter. Basically, the new variant was sidestepping the antibodies COVID survivors had from a prior infection.

Ester Sabino: There is no way to explain what happens in Manaus without thinking that reinfection is probably common.

Céline Gounder: In Manaus, Felipe says several events came together to create the deadly spike in cases that happened in January.

Felipe Gomes Naveca: I think we had the perfect storm that leads to the situation.

Céline Gounder: Rainy weather. Opposition to social distancing measures. Christmas and New Year celebrations. All of these factors could contribute to another spike in cases on their own. Add a new more transmissible variant to the mix, and it’s a disaster.

Felipe Gomes Naveca: So we had a very dramatic situation. We had at least two weeks of total chaos in Manaus.

News Clips:

In Amazonas biggest city, Manaus, hospitals are close to collapse with medical supplies dwindling and intensive care units nearing capacity.

The city’s healthcare system has been overwhelmed, with hospitals running out of beds and oxygen. 

The strain on the system this time, thought to be exacerbated by the new Brazilian variant.

Céline Gounder: The public and private hospitals ran out of room for new patients. There were so many COVID ICU patients in Manaus that hospitals started to run out of oxygen.

Felipe Gomes Naveca: We saw physicians desperate, because they could not do too much for their patients. We had the peak of death at this point because patients with COVID-19, some of those patients really need external oxygen supply. And at this point, several patients died because they did not have access to oxygen.

Céline Gounder: Deaths in Manaus were averaging thirty people a day.

Felipe Gomes Naveca: At the hardest time. We had more than 200 deaths a day in Manaus.

Céline Gounder: The situation was so bad that patients in need of ICU care had to be airlifted out of Manaus to other cities. Some were flown as far away as Sao Paulo, more than 2,000 miles away from Manaus. After those difficult weeks, the situation did start to improve. Hospitals were no longer overflowing with patients after the airlifts started. And Felipe says additional social distancing measures were a big help, too. But the P.1 variant is no longer just in Manaus.

Felipe Gomes Naveca: And now we have several Brazilian States with P.1 detected, like Sao Paulo and Rio de Janeiro, Sierra, Rio Grande do Sul, Santa Catarina. So there are several Brazillian States reporting P.1 right now.

Céline Gounder: This spread, especially into the southeast of Brazil, is a big concern.

Felipe Gomes Naveca: Almost a half of the Brazilian population lives in this area. And so if P.1 spreads like in Amazonas state, I think that we will have a big problem.

Céline Gounder: The B.1.351 variant first found in South Africa has shown increased resistance to the vaccines. The B.1.351 variant and the P.1 variant in Brazil share mutations in common. So, will the vaccines available be effective against the P.1 variant?

Felipe Gomes Naveca: That’s the main question right now. I believe that we will have some losses in efficacy, but I hope that it is still enough to protect against P.1.

Céline Gounder: Trials are on-going, but there is some good news. This month, a study published in the New England Journal of Medicine found that the Pfizer vaccine retained its effectiveness against the UK and Brazil variants. But against the South Africa variant, both the Pfizer and Moderna vaccines elicit lower though still protective neutralizing antibody responses. But that’s still cause for concern. But for now, that’s not what Ester’s most worried about.

Ester Sabino: So the problem with the vaccine is that there is not enough for everybody in the world.

Céline Gounder: The country missed multiple opportunities to place orders for the Pfizer and AstraZeneca vaccines. And though Brazil has been working to manufacture the AstraZeneca vaccine in-country, it hasn’t been able to secure enough raw material from China. Local production may not begin until July. Aside from a small emergency allotment of doses from AstraZeneca, the country has been left with no choice but to purchase the Chinese CoronaVac vaccine, which was barely over 50% effective in clinical trials.

Ester Sabino: Brazil has a public health system that vaccinates a lot of people. So if there were enough vaccines, I’m sure we would be able to vaccinate everybody very quickly. But the thing is, we don’t.

Céline Gounder: The experience in Brazil has a lot to teach the United States. It’s an example of what happens when there’s not an effective response from the government.

Ester Sabino: You cannot just, just think that’s going away because like magic. [laughs] It’s not Disneyland.

Céline Gounder: It also debunks theories that if only enough people got the virus, it could be controlled.

Ester Sabino: This does not create a herd immunity in the sense that we want, that the virus would be controlled naturally. So that’s what Manaus is showing; that this is not something achievable.

Céline Gounder: And finally, it demonstrates why we have to use everything at our disposal to control transmission. That means vaccines but also continuing to wear a mask and limiting exposure to people outside your bubble.

Ester Sabino: I think everybody should be worried and be looking for new variants. I think it might happen in other places. I think we are just seeing the first ones.

Céline Gounder: If cases remain high in the United States… or anywhere else where COVID is raging… there could be another variant just waiting to emerge.

CREDITS

EPIDEMIC is brought to you by Just Human Productions. We’re funded in part by listeners like you. We’re 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 Fagbenle. Our interns are Annabel Chen, Bryan Chen, Julie Levey, and Sophie Varma.

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

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Guests
Ester Sabino Ester Sabino
Felipe Gomes Naveca Felipe Gomes Naveca
Host
Dr. Celine Gounder Dr. Celine Gounder