Scientists have discovered that mutations in the SARS-CoV-2 virus can arise quickly in patients undergoing long-term treatment for the infection, allowing it to evolve into variants that pose new threats to public health.
The study, co-authored by David Pollock, PhD, professor of biochemistry and molecular genetics at the University of Colorado School of Medicine, was published last week in the journal Nature.
“The SARS-CoV-2 virus is evolving and adapting to the point where it can replicate faster and evade the antibody response,” said Pollock. “That’s a real problem because it means that the way we do things now like social distancing, mask wearing, washing our hands may not be good enough, and we have to do more because it’s replicating so fast.”
Cancer patient leads to discovery
The researchers also found that convalescent plasma, which uses antibodies from the blood of those who have had COVID-19, can play a role in the rise of these strains that have mutations in common with the highly infectious UK B1.1.7 variant.
The discoveries were made while treating a man in his 70s for SARS-CoV- 2 in Great Britain. The patient’s immune system had been weakened by cancer treatment. Doctors gave him remdesivir, steroids and convalescent plasma for the coronavirus infection.
The patient initially stabilized but between days 66 and 82, after receiving two rounds of convalescent plasma, doctors discovered that the virus was changing. They observed mutations in the spike protein, the part of the virus used to infect other cells. The mutations quickly disappeared after the plasma treatment stopped, only to reemerge after another course of plasma.
Researchers watched virus evolve
The researchers realized they were watching the virus evolve. Mutations would rise, be wiped out, and rise again.
“The virus was evolving fairly rapidly and adapting to the treatments, especially the plasma,” Pollock said. “There are multiple lines of evidence to support the idea that the plasma caused selection on the variant. And the newly evolved variant protected against convalescent plasma.”
The second mutation of the virus’s spike protein fixed the partial defects in the first mutation, he said.
The patient eventually died.
Researchers created a synthetic version of the spike protein and showed how the changes to its genetic code affected its function. A mutation shared with the UK variant made it more than twice as infectious alone as the more common virus.
Connection to weakened immune system
“Here we have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the study said.
Those with weakened immune systems are more at risk for viral mutations, the researchers added.
The authors also noted that the clinical efficacy of convalescent plasma in severe COVID-19 has not been demonstrated and its use in different stages of the disease remains experimental.
“As such we suggest that it should be reserved for use within clinical trials, with rigorous monitoring of clinical and virological parameters,” they wrote.
‘Real concerns’ about rapidly replicating strains
Pollock said that some of the new virus strains, like one that has emerged in Brazil, carry some of these same mutations.
“There are real concerns that some of these new rapidly replicating virus strains are also more virulent, more likely to damage or even kill you,” he said. “These are all really big concerns. What we did here was show how the virus was making these adaptions. We essentially caught the virus in the act.”
