Sabiá virus mutations evaded detection for decades, USP research reveals

A virus that killed two people in rural Brazil had been quietly changing for more than three decades, slipping past the very tests designed to catch it. Researchers at the University of São Paulo have now documented how the Sabiá virus mutated in the precise genetic regions that diagnostic laboratories were monitoring, which is why the two fatal cases—one a 52-year-old hiker from Sorocaba, the other a 63-year-old farm worker from Assis—went unconfirmed for so long. Both men died after developing severe symptoms: high fever, internal bleeding, kidney failure, neurological damage, and the collapse of multiple organ systems. The discovery raises an unsettling question: how many other people may have died of this virus without anyone knowing?

The problem traces back to 1990, when researchers first identified and sequenced the Sabiá virus from a case in Cotia, a city in São Paulo state. For decades afterward, diagnostic tests were built around that original genetic blueprint. But viruses do not stand still. As the years accumulated—thirty of them, then more—the Sabiá virus was accumulating changes in its genetic code. The mutations were not random. They occurred precisely in the regions of the genome that the old diagnostic tests were designed to recognize and amplify. It was as if the virus had learned to hide in plain sight.

When the two recent cases arrived at hospitals, the standard tests failed to identify them. The patients were sick with something serious, but the laboratory results came back negative for Sabiá. It was only when researchers deployed a more sophisticated technique—metagenomic analysis, which can identify unknown microorganisms by sequencing all the genetic material present in a patient sample—that the virus was finally revealed. Ingra Morales Claro, a researcher involved in the work, explained that once they examined the genomes of these new cases, they found mutations blocking detection by the existing diagnostic primers. The team then modified those primers to match the virus as it actually circulates today.

The researchers also discovered that the virus had altered the proteins it uses to attach to human cells, another sign of significant evolutionary drift. These were not trivial changes. They suggested that the Sabiá virus had been evolving in the environment for a long time, possibly infecting people repeatedly without being caught. Ester Sabino, a virologist at the University of São Paulo's medical school, warned that there were likely other cases in the past that were never identified—people who fell ill and died without anyone recognizing what had killed them.

What remains unknown is almost as striking as what has been discovered. Scientists believe the virus lives naturally in wild rodents, a hypothesis supported by the fact that both confirmed cases occurred in rural areas or near forests. But the exact species has not been identified. The routes of transmission are also unclear. Can the virus spread from person to person? Does it require direct contact with an infected animal? Can it be transmitted through contaminated food or water? These questions remain open. Ana S. Levin, an infectious disease specialist at the University of São Paulo, noted that researchers cannot yet rule out human-to-human transmission, nor can they say with certainty whether milder forms of the disease exist—cases that might resemble a bad flu rather than a hemorrhagic fever.

The implications are sobering. A virus that has been circulating in Brazil for decades, evolving as it goes, has largely escaped scientific attention because the tools used to detect it became obsolete. The two deaths documented in this study may represent only the visible tip of a much larger problem. Going forward, scientists are calling for enhanced surveillance systems and updated diagnostic methods that can keep pace with the virus's genetic changes. Without such vigilance, future cases—or even outbreaks—could go unrecognized until it is too late.