The world has experienced a slew of surges caused by an alphabet of variants since the onset of the COVID-19 pandemic in March 2020. Thankfully, none of the variants has led to a significant increase in disease severity.
Becker's spoke to Jonathan Abraham, MD, PhD, an infectious diseases physician at Boston-based Brigham & Women's Hospital, to learn more about why the SARS-CoV-2 virus's evolution hasn't led to significant changes in disease severity from the ancestral strain, and what are the chances that it eventually mutates to cause severe illness.
"It's something that even as a scientific community, we don't understand yet," Dr. Abraham said. He is an assistant professor of microbiology at Harvard Medical School and runs the Abraham Lab, which studies how pathogens interact with the cells of their hosts.
Two questions that remain:
When will immunity significantly wane?
While each new variant appears to be better at infecting vaccinated people than the last, vaccines have still largely protected against severe illness from each of them.
The question of whether the SARS-CoV-2 virus could eventually evolve to cause more severe illness then depends, at least in part, on the level of immunity a population has.
"Overtime, we've seen this virus mutate and mutate, but the question is still when will the immunity we have either from vaccines or from prior exposure [wane,] and by then, will the virus have disappeared or will it have continued to mutate?" said Dr. Abraham.
If the virus continues to mutate over time and the population's immunity wanes significantly, more severe disease is a possibility, "but the question is really hard to separate from one of the infected host, which has some degree of immunity," he said.
In a vaccine-less world where there were no levels of immunity and a mutating virus, variants like omicron would likely cause severe illness. But in a world where most people have been vaccinated or previously infected, that's not the case.
Could the virus evolve to evade T-cell responses?
Even with the virus able to evade antibodies, there is evidence that T-cells — a separate arm of the immune system's response — play a role in maintaining immunity from COVID-19.
In someone with prior immunity from vaccination, infection or both, "I think most would believe T-cells … probably account for why disease severity is not as significant when someone gets infected now," Dr. Abraham said.
"T-cells are really the work horses that may be protecting us from getting sicker," he said, but if the virus mutates in a way that allows it to evade both antibody and T-cell responses, that may be a recipe for more severe disease.
Some research has shown people who have COVID-19 generate T-cells that target at least 15 to 20 different fragments of SARS-CoV-2 virus' protein, according to a Nature report. The targeted protein fragments can vary widely among different people, meaning a population could generate a broad variety of T-cells against the virus.
"That makes it very hard for the virus to escape cell recognition," Dr. Alessandro Sette at the La Jolla Institute for Immunology in California, told the news outlet, adding its "unlike the situation for antibodies."