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Genomic Analysis Indicates Multiple SARS-CoV-2 Introductions to Northern California

NEW YORK – SARS-CoV-2 was introduced multiple times into Northern California, according to a genomic surveillance study. The finding may inform travel restrictions and other endeavors to contain viral spread.

Using genomic approaches, scientists have been teasing out how SARS-CoV-2 has spread from the initial outbreak in Wuhan, China to other countries as well as within countries and regions. The first reported COVID-19 case in the US was reported in mid-January in the US and that case, like many of the first few cases, was associated with international travel.

Previously, researchers from the Fred Hutchinson Cancer Research Center reported in a MedRxiv preprint that the initial Washington State case in mid-January appeared to be a direct ancestor of later cases in the community, beginning in late February, suggesting cryptic transmission of the virus in the community for a few weeks. A later analysis from KU Leuven researchers in a BioRxiv preprint, though, instead suggested that there were multiple introductions of the virus into the region. Two other groups, meanwhile, reported that many of the SARS-CoV-2 lineages circulating in New York City largely arrived via Europe.

In a new phylogenomic analysis appearing in Science, a University of California, San Francisco-led team analyzed SARS-CoV-2 samples from patients in Northern California to retrace how the virus came to be there. UCSF's Charles Chiu and his team analyzed dozens of patient samples from nine different California counties and the Grand Princess cruise ship and found that more than half a dozen viral lineages have been introduced there.

According to the researchers, their findings could inform efforts at containing the virus. "These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states," they wrote in their paper.

Chiu and his colleagues screened 62 swabs taken from 54 COVID-19 patients in Northern California or on the cruise ship. Using an approach they developed called metagenomic sequencing with spiked primer enrichment (MSSPE) or tiled multiplex PCR, the researchers enriched each sample for the SARS-CoV-2 RNA genome for sequencing on the Illumina NextSeq, HiSeq, or MiSeq machines.

In all, this yielded 34 SARS-CoV-2 genomes with more than 65 percent genome coverage, which they bundled with two additional SARS-CoV-2 genomes from a returning traveler and a household contact

Overall, no one viral lineage appears to be dominant in Northern California, the researchers reported. A phylogenetic analysis of these Northern California SARS-CoV-2 genomes alongside the nearly 790 global SARS-CoV-2 genomes in the GISAID database — as of the researchers’ analysis — placed these viral samples in multiple lineages.

All 11 samples from the Grand Princess cruise ship — the ship made two voyages between San Francisco and Mexico and Hawaii in February and March — were part of the WA1 lineage, the researchers found. In addition to the three SNVs that distinguish that lineage, the cruise ship samples harbored two other SNVs that are also found among members of the WA1 lineage, but that are missing from the initial case.

This and the addition of new mutations among passengers on the second cruise suggested to the researchers that the virus on the Grand Princess cruise ship originated from the Washington State outbreak or other region where WA1 is circulating. Viruses from this lineage were also uncovered in other Northern California locations.

At the same time, they reported three patients who had traveled internationally or were exposed to such travelers had viruses that clustered with the Chinese viral lineages, while five other viral samples clustered with European or New York viral lineages.

Additionally, seven viral genomes from individuals in Santa Clara County clustered together, as did additional cases from Solano and San Mateo counties, suggesting spread across county lines.

Though the researchers noted they are based on a small sample size, these findings indicate travel may have enabled viral spread and that social-distancing measures may help limit transmission. "Suspension of non-essential travel may thus be necessary to prevent ongoing importation of new cases in California and other states," they wrote in their paper.