XBB.1.5 Spreading Rapidly Through the US: Why the Coronavirus Continues to Confound Scientists and Public Health Officials

By Henry I. Miller, MS, MD — Jan 10, 2023
The SARS-CoV-2 virus, which causes COVID-19, is threatening to surge again. In the past few weeks alone, a recent version, XBB.1.5, the most infectious subvariant yet discovered, has quickly spread in the United States. As of the most recent data from the Centers for Disease Control, this variant makes up about three-quarters of all cases in the Northeast and 27.6% nationwide. There is reason to be concerned.

This is a brief excerpt. See the full article here.

The most striking thing about XBB.1.5 is that it didn’t simply arise as the result of point mutations in the RNA; rather it is the result of a recombination of two descendants of the BA.2 variant. Swiss virologist Dr. Emma Hodcroft has made a useful diagram that illustrates what that means:


Credit: Dr. Emma Hodcroft

It might look complicated, but in the upper part of the figure, we need only focus on the horizontal purple and red lines, which represent the RNAs that comprise the genome of two discrete subvariants of the BA.2 variant before recombination occurred. The bottom part of the figure depicts the genome of the new virus, XBB, that resulted from recombination (that is, breakage and reattachment, or what Dr. Hodcroft calls “template switching”). XBB is comprised of genetic material from both of the “parents,” which is shown by the line being both purple and red, joined at the “breakpoint.”

Dr. Hodcroft described the process this way: 

When a virus copies itself, it can ‘template switch’ between different genomes floating around. If those are all the same, the end product isn’t different! But if distinct lineages are there at the same time, we can spot these ‘chimera’ children – recombinants!

This is somewhat similar to what happens when an animal is infected by two different flu viruses. Inside the animal, they exchange RNA fragments to create a new, more dangerous virus which goes on to spread.

Lowering the probability

The important takeaway: For the recombination event to have occurred, the two parental viruses must both have infected a person and have been present in the same cell simultaneously for enzymes to have broken and reattached portions of the two genomes.  

That scientific observation has important implications for public policy: To lower the likelihood of more dangerous subvariants arising in this way, we should strive to lower the probability of such co-infection events. We do that by decreasing the number of infections that occur, and we do that by applying the old 2020 rallying cry: “Flatten the curve.” 


Henry I. Miller, MS, MD

Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.

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