Virus's retreat in Brazilian Amazon upends notions of herd immunity

The human destruction in the Brazilian city of Manaus would be "catastrophic," physician Geraldo Felipe Barbosa feared.

But then, unexpectedly, it started to let up - without the interventions seen elsewhere.

Hospitalizations of coronavirus patients plummeted in the state from a peak of more than 1,300 in May to fewer than 300 in August. Excess deaths in Manaus fell from around 120 per day to practically zero. The city closed its field hospital.

In a country devastated by the novel coronavirus, where more than 3.2 million people have been infected and over 105,000 killed, the reversal has stunned front-line doctors. Manaus never imposed a lockdown or other strict containment measures employed successfully in Asia and Europe. And what policies did exist, many people ignored. 

In the spring, the Amazonian city became a global symbol of the devastation the disease can wreak in the developing world. But now it has returned to near normalcy - far sooner than many expected - and scientists and public health officials are asking why. The question is part of a broader debate among scientists and public health officials over the mechanics of herd immunity and the level of transmission that must be crossed before the disease starts to recede.

European cities that were pummeled by the disease have begun to reopen without crippling second waves. In Guayaquil, the Ecuadoran metropolis where bodies were left on the streets, scientists have cautiously speculated that collective immunity has been reached. Some researchers are now suggesting the same about New York City.

The factors that are helping to keep the virus at bay in Manaus and other cities remain unclear. Changed behaviors and individual community characteristics surely play a role. Manaus is testing far more than it once did. But whatever the dynamic, scientists and health officials are starting to wonder whether early prognostications about herd immunity overshot the mark.

It was initially believed that between 60 and 70% of the population needed to develop antibodies to reach collective immunity. But Guayaquil never broke 33%. Manaus, the capital of Amazonas state, never got past 20.

"Manaus is an interesting case, indeed," said Jarbas Barbosa da Silva, assistant director of the Pan American Health Organization. "The hypothesis - and this is just a hypothesis - is that the peak we had in Manaus was very strong, and there was such widespread community transmission that it may have produced some kind of collective immunity."

Draconian restrictive measures reduce the disease sharply, Barbosa said. But in Manaus, the reduction has been gradual, with a steady progression of new cases still arriving every day. That curve suggests the disease followed a "natural dynamic," Barbosa said.

Manaus, he said, "paid a very large price" to get there. During the spring, it suffered three times as many deaths as normal. In all, the city of 2 million along the Amazon River buried some 3,300 people more than usual.

"This was not a strategy," Barbosa said. "It was a tragedy."

- - - 

The idea of herd immunity has long been used to justify and explain the purpose of mass vaccination campaigns. Scientists would plug the disease transmission rate - or how many people one sick person infects - into a calculation to determine the percentage of people who should be inoculated. For particularly infectious diseases, such as measles, that's as high as 95%. For others, it's lower.

But researchers say collective immunity works differently in a live outbreak. The disease doesn't simply vanish when a magic number is crossed. Instead, as the pool of potential victims shrinks, transmission decelerates until it's gone. Containment policies can lower transmission further. But regardless of whether they're adopted, once the pool of potential victims reaches a critical mass, an explosive resurgence is unlikely. Too many people would have already contracted the disease.

"In Italy, it struck the Milan region very badly," said Tom Britton, a mathematician at Stockholm University. "But not Rome very much. If I had to bet money that there was a second wave, I would bet all of my money on Rome, rather than Milan."

Britton and other researchers have been studying what's known as "heterogeneity in susceptibility." Early herd immunity models - and vaccination campaigns - have operated from the assumption that everyone's the same. But individuals vary: Some people are more socially active, others are more physically vulnerable. Heterogeneity, researchers say, reduces the percentage of infection at which herd immunity may be achieved. The people most likely to get the disease and pass it on - the most socially active, the most susceptible - catch it first. But once they're out of the pool of potential victims, the risk is less for everyone else.

"The effect of their immunity will be bigger," Britton said. 

In a paper published in Science in June, he and other researchers estimated that population heterogeneity shaves the coronavirus herd immunity rate to 43%. Others say it might be lower.

Gabriela Gomes, a mathematician at the University of Strathclyde in Glasgow, has scrutinized European cities overwhelmed by the disease. In a paper she wrote with nine other researchers, which hasn't yet been peer-reviewed, she arrived at a striking conclusion: Herd immunity could be lower than 20%. 

"Without immunity, you would have expected the cases to start growing very soon after interventions were lifted," she said. "That's what we were saying at the time: 'It's premature to lift interventions. Cases will start going up.' But they didn't. And in most cases, they continued going down. It was quite unexpected."

But with the stakes so high - more than 770,000 dead worldwide and so much about the virus still unknown - many researchers have been reluctant to say whether they believe the worst in some of the hardest-hit cities has already passed. No one knows how long immunity lasts. The virus could mutate.

"In Manaus, maybe we're done with it, and that's it," said Jeffrey Shaman, an environmental health scientist at Columbia University. "I would love that as well. But the reality is that it's wishful thinking. It's confirmation bias. We can't pick evidence we hope is true. We have to be very careful about this because it could blow up in your face very quickly."

- - - 

Pietro Pinheiro Alves, a physician in Manaus, knows how quickly that can happen. Despite its physical remoteness in the rainforest, Manaus is one of Brazil's most international cities. Drawn by a free-trade zone, companies from all over the world have put down roots in the Amazon. As the coronavirus spread worldwide, strains from China, Europe and the United States were soon circulating, unseen. 

It didn't take long for the patient surge to overwhelm the hospital system. 

"People are dying in their houses," Pinheiro Alves wept into the phone in early May, when things were at their worst. "They can't get any help in the hospitals."

He felt hopeless. People were still crowding the streets. Officials weren't willing to impose a lockdown. In impoverished Manaus, where many already live on the brink, the mayor said it would lead to social chaos and violence. So Pinheiro Alves spent his off hours trying to jury-rig ventilators.

Manaus Mayor Arthur Virgílio Neto said he "fought for social isolation."

"The attempt failed," he said. "There wasn't real social isolation. People still went out, and it wasn't understood why. In the most difficult hours, I'd go to the field hospital, get stuck in a traffic jam and think, 'Why aren't people home? What are they doing out?' "

Physician Uildéia Galvão saw the result: Every day, there would be a line of ambulances outside her hospital in central Manaus, each holding a patient in need of a bed. Sometimes they sat for hours, waiting for someone to die and relinquish their bed.

At the height of the city's outbreak, there would be three or four lined up. Then one day, it was two. Then one.

"It was the first sign that the number of emergency calls were dropping," Galvão said.

Intensive care units started to clear. Emergency coronavirus calls slowed, dropping from 2,410 in April to fewer than 180 in July. The wail of ambulances quieted. Some scientists said victory was in sight.

"Why Manaus will be the first Brazilian city to defeat the Covid-19 pandemic," wrote a group of researchers from the Federal University of Amazonas. 

Street activity returned to pre-pandemic levels. People flocked to the river to swim and party. Appeals to wear masks: widely ignored. Private schools opened up. Then public. Cases continued to number in the hundreds every day, but far fewer were serious enough to warrant hospitalizations.

"There isn't a concrete explanation," said Henrique dos Santos Pereira, a scientist at the Federal University of Amazonas. Maybe there's an unseen biological immunity in the population. Or the city's relative youth staved off the worst.

"The problem is that we don't know how many people are susceptible," dos Santos Pereira said. "In the beginning, we were thinking it was everywhere, but it doesn't seem like the whole world is susceptible. . . . It is causing us to reconsider the theory of herd immunity."

Virgílio, the mayor, hopes the scientists are right. The medical system in Manaus has failed once. If a second wave does come, he has little doubt what would happen.

"Our capacities would be overwhelmed."