The idea that viruses have a tendency to become weaker over time is simply not true. Smith’s “law of declining virulence” was a 19th-century construct that has been thoroughly debunked, again and again. Without going into the details (again), just take it as a given: There is no evolutionary pressure that tends to make viruses milder over time. In fact, viruses tend to get more contagious. Whether they cause more serious disease, less serious disease, or stay about the same is all a roll of the genetic dice. If the virus could care about things, it wouldn’t care about this. It’s the contagious part that counts.

So stories claiming that COVID-19 will inevitably turn into a cold need to be taken with a grain of salt roughly the size of the Great Pyramid. 

All that said … a new study (still in preprint, not yet peer reviewed) suggests that the omicron variant may not be evolving to be “like a cold,” but it could be different from other COVID-19 variants because it’s is a cold. Or partly a cold.

The study suggests that the reason omicron appears to be so divergent is because it has incorporated portions of another coronavirus entirely. 

Saturday, Dec 4, 2021 · 8:54:52 PM +00:00 · Mark Sumner

Another paper has appeared at virological.org that notes two other insertion segments in omicron. These are suspected to be insertions sourced out of human RNA. 

Both viruses and bacteria are more free about sharing their genetic material than the rigid idea of “species” might suggest. A bacteria that develops resistance to an antibiotic isn’t just at risk of becoming a particular form of “super bug,” it can pass that resistance on to bacteria of completely different forms. Viruses, by the nature of the way they reproduce in the cells of hosts, are prone to picking up bits and pieces of other viruses in that host, as well as sequences from the host organism’s own genetics.

They can also leave something behind. Eight percent of human DNA is thought to consist of segments left behind by ancient viruses that infected the eggs or sperm cells of our ancestors. Another 40% of the human genome consists of repeating strings of DNA that are thought to have been stitched together through the actions of viruses. That’s not “junk DNA.” Among other things, the code that allows mammals to bear live offspring appears to have been generated based on a mutation created by some ancient virus.

The new study, authored by researchers at the medical data firm nference, looks at the types of changes found in what is described as the “heavily mutated” omicron variant. On the spike protein alone, those changes include 37 mutations, “which include six deletion mutations, one insertion mutation, and 30 substitution mutations.”

It’s that insertion mutation—a point where a new sequence of RNA has been added to the structure—that particularly interests these researchers. In trying to find a source for this new sequence, the nference team looked a virus called HCoV-229E. This is one of seven human coronaviruses that have been around for decades, and which all together are responsible for about 15% of what people describe as “catching a cold.” About 65% of people over the age of three have been infected with HCoV-229E at some point in their lives.

It’s in this common virus that the researchers found a match for the chuck of RNA inserted into the spike protein of omicron. That sequence comes from the protein that HCoV-229E uses to attach to human cells. But where SARS-CoV-2 attaches to cells using ACE2 receptors (found in many parts of the body), HCoV-229E attached to a receptor called ANPEP, which is largely found in the small intestine.

The nference team suggests that omicron may evolved in an individual who was infected with both SARS-CoV-2 and HCoV-229E. By mixing up the proteins of these two viruses, omicron may have gained the flexibility to either better attach to the ACE2 receptor, or even to attach to both ACE2 or ANPEP. Either of these could explain why omicron seems to be capable of outcompeting even the extremely contagious delta variant.

The nference team also notes that the point of this insertion isn’t really close to the point where antibodies bind to the virus. But it is at a spot where human T-cells attach in their fight against the virus and, critically, this sequence also appears in human cells (and because that sequence is also in human cells, it means omicron might have lifted this sequence directly from a host). By placing it at the point where T-cells attack the virus, the virus may be camouflaged from those T-cells.

Whether this makes a difference remains unclear, and “further studies will be necessary to understand whether this insertion may help SARS-CoV-2 escape T-cell immunity.”

Current reporting on this paper, like this piece from Reuters, is quick to suggest that since this sequence of RNA comes from a “cold virus,” it could make omicron act like a cold virus.

But the speculation over the effect of this insertion on the virulence of omicron is likely unfounded. The genetic “program” for SARS-CoV-2 has over 30,000 lines. Changing a few of those lines in one section of that code is unlikely to alter its entire performance. But as has become all too common when discussing omicron, we simply don’t know yet.

As of Friday, doctors in South Africa were reporting a surge of patients under the age of five. Medical authorities there also warn that previous infection with another variant does not seem to block omicron, because it has a “substantial ability to evade immunity from prior infection.”

How this related to protections provided by vaccines isn’t yet clear, but everyone should expect the level of protection against infection to be substantially reduced.