In Brazil's jungle metropolis of Manaus, nurse Francinete Simões thought she had seen the last COVID-19 death at the urgent care center where she works in July. Hospitals finally had space to take critical patients again after a violent initial wave of the virus left many of the city's dead in mass graves.

But in recent weeks, Simões says, hospitals are "filling up, and I'm seeing people die again." The state government has now ordered non-essential businesses to close between December 26 and January 10 as a virus containment measure for this city of 2.2 million.

The teeming port city's recent resurgence should sound an international alarm about how widely the virus can spread when poorly controlled, say researchers. One study, which tested blood donations over a series of months to count COVID cases, estimates the virus may have attacked as many as 76% of Manaus residents by October.

"Some people think that the virus will go away immediately once infections reach a herd immunity level," says immunologist Ester Sabino of the University of São Paulo, the lead researcher of the study published in the journal Science Magazine. "But for a while, it just moves slower, continuing to kill people."

While much of the world still faces long waits for a vaccine, says Sabino, if the virus is unchecked, "slower or faster, what's happening in Manaus can happen anywhere." For its part, Brazil's government has yet to announce a clear vaccination timeline.

An Inequality-Laced Petri Dish

A key factor behind Manaus's explosive outbreak is inequality — both in access to adequate housing and access to healthcare — says epidemiologist Jesem Orellana of the Oswaldo Cruz Foundation (Fiocruz), Brazil's national health research institute. More than 53% of households are in tightly packed poor neighborhoods. At the start of the pandemic, Manaus was the only city in its state of 4 million that had intensive care beds, and it suffered from a doctor shortage. Most people seeking care in the city could only reach it via tightly packed boats, which "quickly spread the virus up and down the [Amazon] river," says Fiocruz microbiologist Felipe Naveca, who has sequenced strains of the virus across the state.

Naveca also believes that a high number of virus strains were introduced to Manaus through its international airport; the city is a free trade zone with frequent business traffic from Europe and Asia. He sequenced four strains of SARS-CoV-2 in the state that have not been identified elsewhere in Brazil, but match strains identified in Colombia, Denmark and the United Kingdom.

Manaus first identified a case of the virus on March 13. City authorities responded with physical distancing measures such as moving non-essential city jobs to remote work and suspending licenses for large events. They also increased access to health services, including opening a field hospital, says health department spokesperson Renildo Rodrigues. Public schools closed on March 17, non-essential services were ordered to close on March 23, and nonresident foreigners were banned from flying into the country on March 30. Face masks were not required until May 11.

Orellana describes authorities' overall response to the virus as "slow and deadly." By the end of May, over 2,000 people had died of COVID-19, according to the government's count.

Cellphone data show only around half of Manaus residents practiced physical distancing in April and May. "Many people didn't believe the pandemic was real," says Simões, the nurse. Manaus is a stronghold of voters for Brazil's president Jair Bolsonaro, who has repeatedly dismissed COVID-19 as a "little flu."

On June 1, the state allowed businesses to begin reopening. By the end of the month, COVID-19 deaths had fallen to around five per day from a high of more than 50 per day at the end of April.

Sabino and her fellow researchers, a group from Brazilian, U.K., and U.S. institutions, attribute the decreased deaths in part to growing population immunity.

In June, "the population was more aware, principally due to the high numbers of deaths in April and May 2020, which led them to better adhere to protective measures," says Rosemary Costa Pinto, director of the state's health department. She says that deaths may also have fallen due to an increase in the number of available hospital beds and health workers' improved understanding of how to deal with the virus.

Costa Pinto said she was aware of the study published in Science reporting much higher numbers than the government but would not comment on it. The state's official count of confirmed virus cases is 3.5% of the population.

Questioning The Data Collection Method

While Manaus's scientific community widely considers the state numbers an undercount, some have criticized the Science study's reliance on blood donors to draw conclusions about the wider population, even after the authors mathematically adjusted to account for donors' limited age range (16 to 69) and for the fact that most were men.

In June, a household survey by the Federal University of Pelotas found a much lower rate of residents with COVID antibodies than the blood donor study for the same time period. The Science authors mention the household survey in their article, writing that it was not carried out at a citywide scope and used a less sensitive test. Their own estimate also includes extra calculations to reflect the waning of antibodies over time.

Others, including microbiologist Natália Pasternak, say the study was "very well-conducted work" that acknowledges its limitations and now must be "well-interpreted." Pasternak directs the scientific literacy NGO Instituto Questão da Ciência. "It's not always possible to do a good population sample," she says. "This kind of study is one more scientific tool."

Blood donor studies are currently underway across the world to better understand the pandemic, including in the United States. The Centers for Disease Control and Prevention is conducting a nationwide blood donor survey of SARS-CoV-2 antibodies that is directed by one of Sabino's co-authors, Michael Busch of the Vitalant Research Institute. Busch and Sabino are part of a 20-year partnership between U.S. and Brazilian blood researchers, the REDS Brazil program, backed by the National Institutes of Health.

There is scientific consensus in Manaus about one thing: the outbreak is far from over.

"Everyone must remain on alert," says Quezia Monteiro, an infectologist in the public health system. "People are relaxing, even saying that the pandemic is over in Manaus, which will cost more lives."

Catherine Osborn is a Brazil-based journalist and a frequent contributor to NPR.

Copyright 2020 NPR. To see more, visit https://www.npr.org.

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