What’s Tricky about COVID-19 Variants?

No matter where we come from or what we look like, all humans share the same 99.6% of our DNA. That means that all the beautiful, biologically-driven diversity among people comes from a tiny fraction of our genetic material.
In half of the population–biologic human males–the single Y-chromosome is inherited directly and unchanged from father to son. Because that chromosome never recombines in the process of reproduction, men can theoretically trace their paternal lines and geographic origins back to ancient times. Occasional mistakes do occur, however, when the Y-chromosome is duplicated before being passed onto the next generation, and those variants, or markers, are useful in genealogy.
Similarly, when the SARS-CoV-2 virus that causes COVID-19 multiplies in peoples’ cells, mutations happen at a rate four times faster than with flu infections. Some mutations change the characteristics of its virus (remember, for example, that the original Coronavirus frequently caused loss of smell and taste, but that current variants do so less often.)

With one or more mutations, a group of variants with similar genetic changes may be designated by public health organizations in one of four threat categories due to their characteristics. We often hear about Variants of Concern (VOC), the next to most dangerous category, because such variants may require public health action to prevent further outbreaks and to re-engineer vaccines and treatments.
The dominant COVID-19 variant in the U.S. is XBB.1.5. A VOC, it is a great-grandchild of Omicron, having combined genetic material from two strains of BA.2. The Omicron lineage, which was first found in southwest Africa, is itself a highly mutated offshoot of ancestral SARS-CoV-2 that was identified initially among patients in Wuhan, China.

Coronaviruses typically evolve in a ladder-like pattern from a direct ancestor, and it is notable that since November 2021, all major variants have come exclusively from the Omicron lineage. This is hopeful; we may be settling into a more predictable, endemic-like model, despite each successive Omicron offspring’s being more distinct from its parent and less well neutralized by people’s antibodies.
What makes XBB.1.5 a VOC is that it is more contagious than any previous form of SARS-CoV-2, and it has therefore eclipsed the other more recently dominant Omicron variants. Thankfully, XBB.1.5 does not make us sicker than its immediate predecessors, but it can infect more people because it is better at entering human cells than previous variants. Our existing antibodies do not work very well against XBB.1.5, and for people with immune compromise, the preventive monoclonal antibody, Evusheld, was withdrawn because it is ineffective against this variant.

Fortunately, the antiviral medications Paxlovid and remdesivir continue to work, and our immune system’s T-cells still recognize the main part of the XBB.1.5’s spike protein. This protects most fully boosted people and those who recently had COVID-19 from getting seriously ill.
What keeps epidemiologists awake at night is the possibility that additional variants might pop up from unexpected lines. Omicron didn’t come from Delta, and Delta didn’t come from Alpha. When each of those arrived in the U.S., we experienced big waves of illness because our immune systems were “naïve.” It is still possible that today’s Omicron’s lineage could be swept away by a new random variant that is not a direct descendant, but rather the offspring (think distant cousin) of the original virus.

That is the reason why the bivalent booster shot was designed to cover two bases, nudging our systems to create different antibodies able to attach to both the original virus and to then known Omicron descendants, BA.4 and BA.5.
Ongoing efforts are still needed. First, nations must stop the rampant spread of SARS-CoV-2, especially in places like China, where epidemiologist Dr. Katelyn Jetelina warns, “…[with] the floodgates open in China, there’ll be very little to stop the virus from jumping person to person in this network of 1.4 billion people, [which is] 20% of the global population.”

Although we have no control over how China handles its current COVID-19 humanitarian disaster, we can and should do a better and more equitable job of controlling COVID-19 transmission here. Hence, the call to Vax-Mask-Test-Treat.
Secondly, we need to increase global genomic surveillance, which has fallen 90% since the start of the pandemic. In addition to sequencing virus samples obtained from patients coming to medical facilities, it is also important to test wastewater more universally in the U.S. as well as from aircraft arriving from hotspots around the world. Doing so will help identify new Variants of Concern in time to consider appropriate public health actions.
Finally, making sure that people infected with SARS-CoV-2, whatever the strain, are isolated and treated with appropriate antiviral medications will lessen the likelihood that the virus will spread, or that it will remain in peoples’ bodies long enough to acquire the multiple mutations that could spawn a new and potentially more dangerous variant.

Barbara Hemmendinger, MSS, a member of the Lycoming County Health Improvement Coalition and a retired family medicine educator, belongs to Let’s End COVID!
Published: 2/4/23

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