Medical School Research Details ‘Escape Mechanisms’ Covid Variants Use to Evade Antibodies

A team of researchers at Harvard Medical School detailed how mutated Covid-19 variants can evade both naturally occurring and synthetic antibodies in a study published earlier this month.

The study, titled “SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms,” was published in the journal Cell on March 16.

Jonathan Abraham — the study’s principal investigator and an infectious diseases doctor at Brigham and Women’s Hospital — said that the study was inspired by an immunocompromised patient with a chronic, mutated Covid-19 infection.

Immunocompromised individuals often lack sufficient antibodies to fight off a Covid-19 infection, according to Abraham. This allows the virus to replicate without significant resistance, so the patient ended up with several mutations, according to graduate student and senior author Sarah A. Clark.

The researchers looked at the Covid-19 mutations in the original patient and created safe, non-infectious versions of the virus to work with in the lab.

By working with the “dummy” viruses and selected antibodies, researchers were able to model how Covid-19 can evade immune defenses when multiple mutations are present.

“A single mutation that might pop up in a sequence is not really that big of a deal,” Clark said. “But if the virus continues over time to circulate in the world and has more and more chances to mutate, our paper kind of shows what that effect could be as those mutations accumulate.”

Given the natural accumulation of mutations, Clark said a Covid-19 variant could eventually emerge that evades current vaccines. New, more infectious variants have already cropped up in the U.K., Brazil, and South Africa.

“At a certain point, they’ll stop working. They’ll have to be updated, so kind of like an expiration date in a way,” said Abraham, who is also an assistant professor of microbiology at Harvard Medical School.

Abraham said the health community must remain vigilant in tracking virus mutations as they happen and will need to continue to update both therapeutic antibodies and vaccines.

Lars E. Clark — a graduate student and lead co-author on the paper — said the public should not be too alarmed by their findings. Mutations of Covid-19 are normal, considering the virus has only recently jumped to infect human hosts.

“[The study is] really only looking at the antibody response and that’s only one component of the immune system, so you can’t take too much away from it,” he said. “But I still think it’s an important addition to everything else that’s already out there.”