Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the fourth part of a series of articles on how the virus changes and what that means for humanity. Read the rest: part one, part two, part three, and part four.

Researchers have isolated two new variants of SARS-CoV-2 via genome sequencing in Columbus, Ohio, according to a preprint pending publication on bioRxiv. This is the first study to confirm our fear that variants have been evolving in the U.S. all along—we just haven’t been looking for them. But it won’t be the last. In fact, another preprint of a study conducted in Illinois was published just today.

What follows is an analysis of the soon-to-be-published preprint, sent to me in advance by a colleague at the Wexner Medical Center.

Previously I’ve discussed how the virus changes, through random alterations to its genetic code that accumulate with every passing host. The more viral transmission, the more variants of the virus lurking about. These variants may develop virus-enhancing properties, such as greater infectivity as we’ve seen with the UK and South African variants, or immune resistance, whether from naturally occurring antibodies or vaccines.

The variants sequenced in the Ohio study are distinct from the UK and South Africa strains, B.1.1.7 and 501.V2 respectively, that have spread to most parts of the world. Analysis of their lineage revealed they were in fact native to the United States, evolving from a strain dominant in Columbus. 

The study, conducted by researchers at Ohio State University, examines the genomic sequences of two new variants of SARS-CoV-2 selected from a set of 222 samples taken from April 2020 to January 2021. The first, observed in late December, has several mutations on the S, N, and M proteins. During the week of December 21st, these mutations were detected in 10 percent of samples sequenced. By the following week, the number had risen to 30 percent. The week after that, it was a staggering 60 percent—an increase steep enough to suggest the variant was highly contagious.

A second potentially troubling variant, COH.20G/501Y, was also identified—this time possessing two mutations seen in the UK variant, N501Y and ORF8 R521. The N501Y spike protein mutation is thought to increase the transmissibility of the virus, though ORF8 R521 might also have a part to play. This variant is likely highly infectious. However, unlike the first variant, this was only isolated in one sample. While the sample size is so small the variation could be the consequence of a super-spreader event, the selection for advantageous mutations suggests a broader arc of evolution.

More than anything, the Ohio study underscores the old adage that when you look, you will find. Now that we’re ramping up our ability to surveil the virus and follow our leads, we must also pivot from a place of complacency to one of heightened vigilance. The goal is to anticipate and prevent further circulation of new variants, rather than forever trailing behind. Though we can’t predict the precise mutations to come, we can look specifically for patterns that spell out certain dangers, such as increased contagiousness, virulence, or immune escape.

Another lesson we can learn from the Ohio study is that the current focus on the envelope of the spike protein is much too narrow. Rather than tunnel in solely on the spike, we should expand our sights to include the entire genome. SARS-CoV-2 produces a number of proteins that go by the generic name open reading frame gene (orf), followed by a number and sometimes an additional letter to distinguish one from the other. Though we don’t know as much about them as the spike protein, for all we know orf genes like ORF8 could have a critical role in increasing the fitness of new variants. So could other structural proteins and non-structural proteins that have so far been excluded from the scope of investigation.

These new Ohio variants and others that will likely be isolated in the near future may shed light on the aggressive rise in cases the US has faced in recent weeks. Sharing similar mutations to the UK variants, which have been confirmed to increase transmissibility and is the root cause of the UK’s current lockdown, suggests a similar rise in transmissibility is occurring in the US. As the number of people infected increased, and as the virus encountered mixed states of immunity full and partial, the virus has had ample opportunity to spread, mutate, and enhance its viral strength. Those opportunities will only continue to grow if not countered with rigorous public health measures and continuous vaccination.