Covid-19 mutations on rise
DURING those terrifying early days of the pandemic, scientists offered one piece of reassuring news about Covid19 – it mutated slowly. The earliest mutations did not appear to be consequential. A vaccine, if and when it was invented, might not need regular updating over time. This proved overly optimistic.
Covid-19, Sars-CoV-2, has had billions of chances to reconfigure itself as it has spread across the planet, and it continues to evolve, generating new variants and sub-variants at a clip that has kept scientists on their toes. Twoand-a-half years after it first spilled into humans, the virus has changed its structure and chemistry in ways that confound efforts to bring it fully under control.
And it’s not showing signs of settling down into a drowsy old age. Even with all the changes so far, it still has abundant evolutionary space to explore, according to virologists. What that means in practical terms is that a virus that’s already extremely contagious could become even more so.
“This virus has probably got tricks we haven’t seen yet,” virologist Robert F Garry of Tulane University said. “We know it’s probably not quite as infectious as measles yet, but it’s creeping up there, for sure.”
The latest member of the rogue’s gallery of variants and subvariants is the ungainly named BA.2.12.1, part of the omicron gang. Preliminary research suggests it is about 25% more transmissible than the BA.2 subvariant that is dominant in the US, according to the Centers for Disease Control and Prevention (CDC). The CDC said the subvariant has rapidly spread in the north-east especially, where it accounts for the majority of new infections.
“We have a very, very contagious variant out there. It is going to be hard to ensure no one gets Covid-19 in America. That’s not even a policy goal,” US President Joe Biden’s new Covid-19 co-ordinator, Ashish Jha, said.
He was answering a question about US Vice-President Kamala Harris, who recently tested positive for the virus and went into isolation. Harris had recently been boosted for the second time – her fourth shot of vaccine.
Her case highlights what has become painfully obvious in recent months – no amount of vaccination or boosting can create a perfect shield against infection from Sars-CoV-2. What the vaccines do very well, however, is greatly reduce the risk of severe illness.
But the variants that have emerged can evade many of the neutralising antibodies that are the immune system’s front line of defence.
“It’s evolving at a fairly rapid rate,” said Jesse Bloom, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle. “I do think we need to aggressively consider whether we should update vaccines, and do it soon.”
BA.2.12.1 brings the Covid-19 up another step on the contagiousness scale. Its close relative, BA.2, was already more transmissible than the first omicron strain that hit the country in late 2021. And omicron was more transmissible than delta, and delta was more transmissible than alpha, and alpha was more transmissible than earlier variants that did not have the glory of a Greek alphabet name. Most mutations are not advantageous to the virus.
There are two fundamental ways that the virus can improve its fitness through mutation. The first could be described as mechanical: it can become innately better at infecting a host. Perhaps it improves its ability to bind to a receptor cell. Or perhaps the mutation allows the virus to replicate in greater numbers once an infection has begun – increasing the viral load in the person and, commensurately, the amount of virus that is shed, potentially infecting other people.
The other strategy involves the workaround of immunity. The human immune system, when primed by vaccines or previous infection to be alert for a specific virus, will deploy antibodies that recognise and neutralise it. But mutations make the virus less familiar to the immune system’s frontline defence. The omicron subvariants keep coming: scientists in South Africa have identified BA.4 and BA.5, which have mutations that were seen in earlier variants and are associated with immune evasion. Caseloads there are rising. New laboratory research, not yet peer-reviewed, indicated that the emerging subvariants are adept at eluding the neutralising antibodies seen in people who recovered from infections with the original omicron variant. The authors of the study concluded that BA.4 and BA.5 have the “potential to result in a new infection wave”.
Garry noted that mutations in the virus did not change its appearance dramatically. Garry has a software program that allows him to create a graphic image of the virus, and even rotate it, to observe the locations of mutations and draw inferences for why they matter. He noted that BA.2.12.1 has a mutation, named S704L, that probably destabilises a portion of the spike protein on the virus’s surface. That essentially loosens up part of the spike in a way that facilitates infection. This S704L mutation distinguishes this subvariant from BA.2.
Between vaccinations and infections, there aren’t many people entirely naive to the virus. The latest CDC data suggest the virus has managed to infect nearly 200 million people in the US, which has a population of about 330 million. Among children and teenagers, about three out of four have been infected, the CDC estimates.
For the new CDC study, researchers looked at blood samples from thousands of people and searched for an antibody that is found after a natural infection, but not found after vaccination. The CDC concluded that the omicron variant managed to plough through the US population during the winter almost as if it were an entirely new virus. The country by then was largely vaccinated. And yet 80 million people became infected for the first time in that omicron wave.
Omicron is a distant cousin of delta, alpha and the other variants that had spread earlier – it came out of virologic left field. No one is sure of the origin of omicron, but many disease experts assume it came from an immunocompromised patient with a very lengthy illness, and the virus continued to use mutations to evade the immune system’s efforts to clear it.
Omicron was mercifully less likely to kill a person than previous variants. But infectious disease experts believe future variants could be more pathogenic.