The coronavirus, 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 pace that kept scientists on their toes. Two and a half years after it first spread to humans, the virus has repeatedly altered its structure and chemistry in ways that confuse efforts to fully contain it.
And he shows no signs of settling into a sleepy old age. Even with all the changes so far, it still has abundant evolutionary space to explore, according to virologists who follow it closely. Concretely, this means that an already extremely contagious virus could become even more so.
“This virus probably has tricks that we haven’t seen yet,” said virologist Robert F. Garry of Tulane University. “We know it’s probably not quite as contagious as measles yet, but it sure is going up.”
The final member of the rogue’s gallery of variants and subvariants is the awkwardly 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 currently nationwide dominant, according to the Centers for Disease Control and Prevention. The CDC said the subvariant has spread rapidly in the northeast in particular, where it accounts for the majority of new infections.
“We have a very, very contagious variant there. It’s going to be hard to make sure no one is covid in America. It’s not even a political goal,” President Biden’s new covid-19 coordinator, Ashish Jha, said during his inaugural press briefing on Tuesday.
He was responding to a question about Vice President Harris, who recently tested positive for the virus and went into self-isolation. Harris had recently been boosted for the second time – her fourth injection of the vaccine.
His case highlights what has become painfully clear in recent months: no amount of vaccination or booster can create a perfect shield against SARS-CoV-2 infection. What vaccines do very well, however, is significantly reduce the risk of serious disease. This is extremely important in terms of public health, as is the wider use of therapeutic products, such as the antiviral Paxlovid.
The vaccines currently being deployed were all based on the genomic sequence of the original strain of the virus that spread in late 2019 in Wuhan, China. They essentially mimic the spike protein of this version of the virus and trigger a protective immune response when the real virus appears.
But the variants that have emerged can evade many neutralizing antibodies that are the immune system’s first line of defense.
“It’s moving at a pretty rapid rate,” said Jesse Bloom, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle. “I think we need to look aggressively at whether we need to update vaccines and do that soon.”
BA.2.12.1 takes the new coronavirus up a notch 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 lacked the glory of a Greek alphabet name.
Most mutations are not beneficial to the virus. But when a mutation offers an advantage, the process of natural selection will favor it.
The virus can improve its fitness by mutation in two basic ways. The first could be described as mechanical: it can become naturally better at infecting a host. Perhaps it enhances 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 correspondingly the amount of virus that is shed, potentially infecting others. people.
The other strategy involves the immunity workaround. The human immune system, when primed by vaccines or previous infection to be alert to a specific virus, deploys antibodies that recognize and neutralize it. But the mutations make the virus less familiar to the immune system’s frontline defense.
The omicron subvariants keep coming: Scientists in South Africa have identified BA.4 and BA.5, which have mutations seen in earlier variants and are associated with immune evasion. The number of cases is increasing there. New lab research, published online Sunday but not yet peer-reviewed, indicated that the emerging subvariants are adept at evading the neutralizing antibodies seen in people who have recovered from infections with the original variant of the virus. ‘omicron. The study authors concluded that BA.4 and BA.5 have the “potential to lead to a new wave of infection”.
“Evolution is much more rapid and expansive than we originally estimated,” said Michael T. Osterholm, an infectious disease expert at the University of Minnesota. “Every day I wake up, I’m afraid there’s a new subvariant that we’ll have to consider. … We’re seeing subvariants of subvariants.
Garry, the Tulane scientist, points out that mutations in the virus do not dramatically change its appearance. In fact, he said, even the heavily mutated variants don’t look much different from the original Wuhan strain, or different from other cold-causing coronaviruses. These are subtle changes.
Garry has software that allows him to create a graphical image of the virus, and even rotate it, to observe the locations of mutations and draw conclusions about their significance. On Friday, when asked about BA.2.12.1 and why it spreads, he noted that it has a mutation, named S704L, which likely destabilizes part of the spike protein on the surface of the virus. This basically loosens part of the tip in a way that makes it easier for infection.
This S704L mutation distinguishes this subvariant from BA.2.
The “704” refers to the 704th position of an amino acid in a chain of approximately 1,100 amino acids that make up protein. The S is a type of amino acid (“serine”) seen in the original strain of the virus, and the L (“leucine”) is what is after the mutation. (The mutation is caused by a change of one nucleotide, or “letter,” in the virus’s genetic code; three nucleotides code for one amino acid.)
The virus is spreading in the United States today in a very different immunological landscape from the one it encountered in early 2020. Between vaccinations and infections, few people are completely naive to the virus. The latest data from the CDC suggests that the virus has managed to infect nearly 200 million people in the country, which has a population of about 330 million. Among children and teens, about three in four have been infected, the CDC estimates.
For the new CDC study, researchers looked at blood samples from thousands of people and looked for an antibody found after natural infection, but not found after vaccination. The CDC concluded that the omicron variant managed to cross the population of the United States during the winter almost as if it were an entirely new virus. The country was then largely vaccinated. And yet, around 80 million people were first infected during this omicron wave.
On the family tree of this coronavirus, omicron is a distant cousin of delta, alpha and the other variants that had spread earlier — it came out of the virological left field. No one is sure where the omicron came from, but many disease experts assume it came from an immunocompromised patient with a very long illness, and the virus continued to use mutations to evade the virus. efforts of the immune system to eliminate it.
Omicron was fortunately less likely to kill a person than previous variants. But infectious disease experts are clear on this point: future variants could be more pathogenic.
As if mutation weren’t enough of a problem, the virus has another trick up its sleeve: recombination. This occurs when two distinct strains simultaneously infect the same host and their genes become entangled. The recombination process is the origin of what is called omicron XE. This recombinant likely emerged from a person co-infected with the original omicron variant and the BA.2 subvariant.
This has always been possible in theory, but identifying true recombinants provides “proof of concept,” as Jeremy Luban, a virologist at the University of Massachusetts Medical School, puts it.
The worst-case scenario would be the emergence of a variant or recombinant that would render current vaccines largely ineffective in blocking severe disease. But so far this has not happened. And no “recombinants” have spread like omicron or other recent variants and subvariants.
This is the first catastrophic pandemic to occur in the era of modern genomic sequencing. A century ago, no one knew what a coronavirus was, and even a “virus” was a relatively new concept. But today, with millions of samples of the virus analyzed at the genetic level, scientists can track mutations in near real time and observe how the virus evolves. Scientists around the world have uploaded millions of sequences to the database known as GISAID.
Genome sequencing has a major limitation in that, although scientists can track changes in the genome, they don’t automatically know what each of those changes does to the virus. Which mutations matter most is a question that can be discerned by laboratory experiments, modeling or epidemiological surveillance, but it is not always straightforward or obvious.
Erica Saphire, president of the La Jolla Institute of Immunology, speculates that omicron has mutations that have altered the virus in ways not yet understood but that make it more resistant to antibody-mediated neutralization.
“He may have picked up a new trick that we haven’t discovered yet,” Saphire said. “It’s harder to neutralize than I expected, based on the number of mutations alone.”
A reality check comes from Jeremy Kamil, associate professor of microbiology and immunology at Louisiana State University Health Shreveport: “It’s all SARS-CoV-2.”
What he means is that they are all variants of the same virus, despite what appears to be a huge amount of mutations. As a result, a person infected with one of these new variants has the same disease as previously infected people.
“They became covid,” he said.