Professor Marc Johnson of the University of Missouri has done a lot of research on so-called cryptic lineages of SARS-CoV-2, highly genetically distinct variants which do not match strains circulating in the wider population. They are usually identified when weird genetic signals start appearing in wastewater surveillance.
Though cryptic lineages are by definition difficult to track, they are thought to emerge in immunocompromised individuals with exceptionally long-lived infections. The viruses inside them can go through countless rounds of replication and selection, evolving independently of the selective pressures acting on viruses transmitted through the wider population. For example, in 2022 Johnson and his team managed to track a cryptic lineage in Wisconsin from an area covering more than 100,000 people to a single commercial building with about 30 employees, at least one of whom was shedding extraordinary amounts of viral RNA.
The weirdest of these lineages is probably one in Lincoln, Nebraska. Johnson describes it as having been detected in nearly every sample from the city for the past few years and as descending from a pre-Delta strain, suggesting a continuous infection lasting at least five and a half years. Its receptor-binding domain, the part of the spike protein that binds to human cells and is a major target of antibodies, is the most divergent on record.
If Johnson is right, someone’s chronic infection has produced a private branch of the SARS-CoV-2 family tree.