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 subvariants at a clip that has kept scientists on their toes. Two-and-a-half years after it first spilled into humans, the virus has repeatedly 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 who are tracking it closely. What that means in practical terms is that a virus that’s already extremely contagious could become even more so.
The vaccines currently 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 that version of the virus and trigger an immune response that is protective when the real virus shows up.
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 recognize and neutralize it. But mutations make the virus less familiar to the immune system’s front-line defense.
“The evolution is much more rapid and expansive than we initially estimated,” said Michael T. Osterholm, a University of Minnesota infectious-disease expert. “Every day I wake up, I fear there will be a new subvariant that we will have to consider. … We’re seeing subvariants of subvariants.”
Garry, the Tulane scientist, points out that mutations in the virus do not change its appearance dramatically. In fact, he said, even the heavily mutated variants don’t look much different from the original Wuhan strain, or different from other coronaviruses that cause common colds. These are subtle changes.
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. On Friday, asked about BA.2.12.1, and why it is spreading, he noted it has a mutation, named S704L, that probably destabilizes 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.
The “704” refers to the 704th position for an amino acid on a chain of roughly 1,100 amino acids that form the protein. The S is one type of amino acid (“serine”) seen in the original strain of the virus, and the L (“leucine”) is what is there after the mutation. (The mutation is caused by a change in one nucleotide, or “letter,” in the genetic code of the virus; three nucleotides encode for an amino acid.)
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 plow through the United States 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, approximately, became infected for the first time in that 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 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.
As if mutation wasn’t enough of a problem, the virus has another trick up its sleeve: recombination. It happens when two distinct strains infect a single host simultaneously and their genes becoming entangled. The recombination process is the origin of what’s known as omicron XE. That recombinant probably emerged from a person co-infected with the original omicron variant and the BA.2 subvariant.
The worst-case scenario would be the emergence of a variant or recombinant that renders current vaccines largely ineffective at blocking severe disease. But so far, that hasn’t happened. And no “recombinant” has spread like omicron or other recent variants and subvariants.
This is the first catastrophic pandemic to occur in the age 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 virtually in real time and watch the virus evolve. Scientists across the planet have uploaded millions of sequences to the database known as GISAID.
Genomic 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 is doing to the virus. Which mutations matter most is a question that can be discerned through laboratory experiments, modeling or epidemiological surveillance, but it’s not always simple or obvious.
What he means is that these are all variations of the same virus, despite what seems like a tremendous amount of mutation. Correspondingly, someone who gets infected with one of these new variants has the same disease as people who got infected previously.
This content was originally published here.