Two emergent subvariants appear to dodge natural immunity

In the past week, cases of a new variant of the Omicron strain of COVID-19 have tripled in South Africa, two cases have shown up in the United States, and others have appeared in Denmark, Scotland and England. While BA.4 is making its way to other countries, BA.5 has been slower to leave South Africa and Botswana.

The World Health Organization last month added the two subvariants to its monitoring list, but said it was tracking just a few dozen cases globally.

The two new sublineages can dodge antibodies from earlier infection well enough to trigger a new wave, but are far less able to thrive in the blood of people vaccinated against COVID-19, South African scientists found.

“What we are seeing now, or at least maybe the first signs, is not completely new variants emerging, but current variants are starting to create lineages of themselves,” Tulio de Oliveira, director of the KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP), told the New York Times. Omicron has produced several subvariants since it was identified in South Africa and neighbouring Botswana in November.

KRISP, part of a virus-research network across South Africa, was able to identify the Beta and Omicron variants because of the knowledge gained from the continent's fight against HIV.

De Oliveira said BA.4 and BA.5 demonstrate how the virus is evolving as global immunity increases. It appears that in unvaccinated people, the new subvariants evade a person's natural immunity produced from an infection with the original Omicron variant, BA.1. The two new variants have sprang from BA.1.

Researchers took blood samples from 39 participants previously infected by Omicron when it first showed up at the end of last year. Fifteen were vaccinated — eight with Pfizer's shot; seven with J&J's — while the other 24 were not. “The vaccinated group showed about a five-fold higher neutralization capacity ... and should be better protected,” said the study.

In the unvaccinated samples, there was an almost eight-fold decrease in antibody production when exposed to BA.4 and BA.5, compared with the original BA.1 Omicron lineage. Blood from the vaccinated people showed a three-fold decrease.

About 90 per cent of the South African population has some immunity, most from a previous infection. But as this immunity begins to wane at around three months — and with mask-wearing down and travelling up — the number of reinfections is increasing. The country's National Institute for Communicable Diseases reported nearly 4,000 new infections on Sunday alone.

Lifting public health restrictions also increases the risk of multiple strains of SARS-CoV-2 co-circulating and recombining, Horacio Bach, an infectious disease expert at University of British Columbia, told the Canadian Medical Association Journal last week. “As long as you have (facilities) open now — no mask on and nothing — the potential that you generate new mutants, variants or new recombinants is always open,” he said.

Those who contract one of the new variants may well get sick, but probably won't require hospitalization or die, Africa Health Research Institute professor Alex Sigal told Fortune. But he added that those who had COVID prior to Omicron likely don't have much immunity to BA.4 and BA.5, nor will those infected with Omicron but not vaccinated.

“It could go either way” for them, he said.

The earliest sample of BA.4 in the U.S. was collected on March 30. The earliest sample of BA.5 in the U.S. was collected March 29.

A new BA.4/BA.5 wave is “a strong possibility,” given the subvariants' increased transmissibility and their ability to evade antibodies, Sigal and his team wrote in their study.