Is Omicron the Start of the End?

Despite mankind’s sophistication, the Omicron COVID-19 variant just surprised us once again with the lesson that we remain an earthly species, decidedly non-exempt from nature’s whims. 

Given the pace of Omicron developments, you will probably know much more about the virus when you read this than I do as I write. All we now understand for sure is that the new variant has an unusually large number of mutations and appears to be spreading rapidly. More mutations mean major divergence from the parent strain, making it less predictable.   

Variants produced by viral mutations may affect us adversely in three possible ways: they can make the virus more contagious; they can increase the severity of the disease; and they can reduce the protection afforded by the vaccines that targeted the parent strain. Although it would be unlikely, a variant producing adverse changes in all three areas could set us back to the beginning of the pandemic: A highly contagious and lethal virus spreading among a population without protective immunity.

The most contagious strains “win.” But increased contagiousness also has the potential to make the disease milder.

Fortunately, the direction of the pandemic, as determined by these mutations, is likely to be much more benign than that frightful scenario. The driving force producing the variants is their ability to compete with other strains in spreading. The most contagious strains “win.” But increased contagiousness also has the potential to make the disease milder. The most important reason is that a virus spreads more effectively if it allows those infected to remain healthy enough to continue spreading it. So, milder strains should have a competitive advantage. 

Mutations that enhance the ability of a virus to spread have random effects on the severity of the resulting disease. But for a virus as lethal as COVID, random change is likelier to reduce severity. 

The fact that random mutations during viral evolution can produce milder disease provided the basis for the development of the Sabin Polio vaccine. Scientists passed the virus through a series of cultures allowing it to replicate. As the virus developed mutations, it became progressively attenuated until it could no longer produce significant neurologic disease. However, it retained enough similarity to the parent virus that when ingested (often on a sugar cube, as you may remember) it could still produce immunity to the more dangerous parent virus strain. Similarly, COVID-19’s passage through successive human populations may select out contagiousness while reducing severity.   

There may be evidence for the emergence of milder yet more contagious variants in the spread of the new variant AY.4.2 in England. Within weeks of the first reports, it accounted for about 10% of new infections in England and seems to produce milder illness. Whether the Omicron strain proves similar to AY.4.2 in this respect remains uncertain. The large number of mutations make it more of a wild card. 

Unfortunately, the mutations that might make new variants milder are less likely to leave vaccine protection unaffected. Mutations increasing contagiousness are largely those affecting the “spike protein,” the part that attaches to human cells. These same proteins also provide the immune target for the vaccines. The more the spike protein changes the less it resembles the original spike and the less likely that vaccine-related antibodies against it can be relied upon to be protective. If the protection fades significantly, a new vaccine against the variant may be needed. 

If milder variants do gain predominance, the pandemic may be gradually heading toward new status as an endemic illness resembling a mild flu or cold. It already plays out that way in most vaccinated individuals. This viral paradigm may represent business-as-usual for human-viral relations over the eons. The cold and flu viruses that circulate among us every winter may be the burned-out remnants of the lethal pandemics of our past.

In a past column, I outlined how my wife’s cousin dismissed last year’s super-spreader Thanksgiving, commenting that “it’s just a cold.”  Ironically, only a capricious virus like COVID-19 could turn such stark ignorance into possible prescience.

Daniel Stone is Regional Medical Director of Cedars-Sinai Valley Network and a practicing internist and geriatrician with Cedars Sinai Medical Group. The views expressed in this column do not necessarily reflect those of Cedars-Sinai.