By Brenda Goodman and Roxana Tabakman
The uncontrolled spread of the most contagious variants of SARS-CoV-2 in Brazil appears to have created even more dangerous versions of the virus that causes COVID-19.
The changes are documented by a team of researchers from FIOCRUZ, a public health research laboratory run by Brazil's Ministry of Health.
The findings were recently published in a preprint on Virological.org , ahead of peer review.
The study describes 11 SARS-CoV-2 sequences from five different Brazilian states. Each had changes in the receptor-binding domain, making it one of the known variants of concern or variants of interest. Each also had additional changes in another important region of the virus: the N-terminal domain.
The changes in the N-terminal domain were deletions of important antibody-binding sites. Many of these were key deletions around Y144, a mutation that has arisen independently in other circulating variants and has been documented in viral mutations in convalescent cancer patients, suggesting that it confers an important advantage to the virus.
The FIOCRUZ team's model suggests that the eliminations will further alter the antibodies' ability to trap the virus and prevent it from infecting cells.
"These findings highlight the urgent need to address the efficacy of SARS-CoV-2 vaccines against emerging SARS-CoV-2 variants and the ongoing risk of uncontrolled community transmission of SARS-CoV-2 in Brazil for the generation of more transmissible variants," the study authors write.
You need to "Turn off replication"
Brazil is in the midst of another devastating wave of COVID-19 infections, fueled by variants and political inaction. Hospitals have run out of beds and other key supplies, such as ventilators and oxygen, and Brazilian President Jair Bolsonaro has rejected the idea of asking citizens to wear masks and refuses to implement lockdowns, saying the price for the country's economy would be too high.
Researchers who were not involved in the study said the findings should put the rest of the world on alert.
John Mellors, MD, chief of infectious diseases at the University of Pittsburgh School of Medicine in Pennsylvania, said the finding "is not surprising, but it is concerning."
Mellors and his colleagues were part of a team of researchers who documented one of the same changes, a deletion at position 144 of the N-terminal domain, in a patient who battled the virus for more than 2 months.
Over time, genome sequencing revealed that the patient, who was treated with convalescent plasma and the antiviral drug remdesivir to try to boost his immune response, was the host of at least six different variants of SARS-CoV-2. These variants had many of the mutations carried by the concerning variants that have emerged in the UK, South Africa, and Brazil.
The N-terminal domain deletions documented in the new preprint have also been detected in other parts of the world.
"The fact that the same deletions are selected, independently of one another, really suggests that these domains are really important for antibody neutralization," said Kevin McCormick, PhD, a postdoctoral researcher in infectious diseases at the University of Pittsburgh School of Medicine.
A separate study , published earlier this month in the journal Science , found that deletions at position 144 disrupt the binding of antibody 48A.
In response to an infection or a vaccine, our bodies produce a whole array of Y-shaped antibodies designed to bind to a virus in slightly different locations. Therefore, losing one of these antibody-binding sites on the virus, in itself, isn't necessarily cause for alarm. But the more SARS-CoV-2 changes shape, the more our immune defenses lose their collective strength, and ultimately, these changes allow the virus to cause reinfection or override the protection provided by a vaccine.
At this time, according to the Centers for Disease Control and Prevention, which is tracking variants, there are no virus variants that cause tests, vaccines, or treatments to fail completely.
"The biggest move we all need to make is to vaccinate to stop the virus from replicating," Mellors said. "No replication, no evolution. So if we shut down replication and spread, we'll be fine, and that's a huge, huge task worldwide."
Sources:
John Mellors, MD, Chief of Infectious Diseases, at the University of Pittsburgh School of Medicine, Pittsburgh, PA
Virological.org. Published on March 18, 2021.