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

The health system in Manaus was collapsed. We had a very, very hard situation at the beginning of January.

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

Science is the only thing that we can use against such an important enemy like this virus.

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. 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.

It's the capital of the state of Amazonas, and it has become an example of the failure Brazil has to cope with COVID-19.

Medical staff describe an overwhelming health 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.

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.

Manaus is like an island because we have the forest on the side and also a big river on the other side.

That's Felipe Gomes Naveca. The jungle is visible across the city. And you can hear the birds through the window of Felipe's office.

I don't know in English, but in Brazil we call it pardal. There are a lot of those birds nearby.

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.

There are at least 4 people from my team lost all mother or an uncle or father.

Felipe was one of them too.

At the first wave, I lost my father due to COVID-19. So it was really something really hard for me. I did his PCR, so I was really involved in this 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.

The pandemic was so out of control, Felipe had to be back at work just 2 days after his father died.

We didn'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.

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

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.

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.

I'm very worried about these new variants.

Why herd immunity from natural infection wasn't protective.

The virus had the chance to evolve for too long, and that's what we are seeing now.

And why, even with vaccines, we can't let our guard down.

This is a war. It's an invisible war. And if we don't use all our weapons, we're not gonna win it.

Today on Epidemic: Manaus and the limits of herd immunity. Esther Sabino is a researcher and physician in São Paulo. Before the pandemic, Esther 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.

So all the idea was to get sequences from the virus quickly enough to give some information for the public health.

So when the coronavirus arrived in Brazil, Esther and her team shifted their attention.

We were responsible for sequencing the first case. So the first case arrived through a person traveling from Italy to São Paulo.

It was Carnival. 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 Bolsonaro, 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 Esther and her team had an idea: the blood banks.

But in Brazil, the blood banks save their samples. Mandatory to save for 6 months. So we were able to get a grant and start doing serological tests since the beginning of the epidemic.

So Estra'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. São Paulo and Manaus were the first cities Estra looked at. She estimated that around 30% of São Paulo had been infected by October 2020. But Manaus was worse. Much worse.

About 50% of the population had antibody in June.

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

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

75%. These are dizzyingly high infection rates. For comparison, as of November, before the winter surge, about 20% of New York City's population had been infected. Esther says they don't know for sure why Manaus got hit so hard, but she has a guess.

The number of people per house in Manaus is higher than the number of people per house in São Paulo.

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.

And maybe the way that the epidemic is transmitted is inside people's house.

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 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.

It was really dramatic in the mid of December. So there is something that seems to be something new.

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.

To our surprise, it was a new VOC.

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. 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.

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.

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. Both variants have similar mutations on the receptor binding domain, the part of the spike protein that attaches to human cells. 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.

So it's a combination of mutations that really help the virus to transmit more rapidly and to escape previous antibody.

Esther 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.

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

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

I think we had the perfect storm that led to this situation.

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.

So we had a very dramatic situation. We had at least 2 weeks of total chaos in Manaus.

In Amazon's 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. The strain on the system this time thought to be exacerbated by the new Brazilian variant.

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.

We saw physicians desperate because they could not do too much for that patients. We had the peak of deaths at this point because patients with COVID-19, some of those patients really needs external oxygen supply. And at this point, several patients died because they did not have access to oxygen.

Deaths in Manaus were averaging 30 people a day.

At the hardest time, we had more than 200 deaths a day in Manaus.

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 São 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 airlift started. And Felipe says additional social distancing measures were a big help, too. But the P.1 variant is no longer just in Manaus.

And now we have several Brazilian states with P.1 detected, like São Paulo, Rio de Janeiro, Ceará, Rio Grande do Sul, Santa Catarina. So there are several Brazilian states reporting P.1 right now.

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

Almost half of the Brazilian population lives in this area. And so if P.1 spread like it was in Amazonas state, I think that we will have a big problem.

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?

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

Trials are ongoing, 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 Esther's most worried about.

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

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.

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

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.

You cannot just, just think that's going away like magic. It's not Disneyland.

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

This does not create 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.

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.

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.

If cases remain high in the United States or anywhere else where COVID is raging, there could be another variant just waiting to emerge. 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 Annabelle Chen, Brian Chen, Julie Levy, and Sophie Varma. If you enjoy the show, please tell a friend about it day. 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 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. Celine Gounder. Thanks for listening to Epidemic.