California currently has the third largest number of COVID-19 cases (roughly 131,000) with less than half of New York and just slightly less than New Jersey. An investigation into the genomic epidemiology of SARS-CoV-2 in northern California suggests that, distinct from virus transmission patterns identified elsewhere, virus arrived in northern California through a complex series of introductions, not only from state to state but also from international travel.

A large collaborative effort analyzed SARS-CoV-2 genomes from a small number of California-based patients from late January to mid-March 2020, taken from 36 patients spanning nine counties and the Grand Princess cruise ship.

The work is published in Science in the paper, “Genomic surveillance reveals multiple introductions of SARS-CoV-2 into northern California.

Though genomic epidemiology of emerging viruses has proven useful for tracking virus evolution and transmissions, in California, real-time genomic epidemiology data of COVID-19 to inform public health interventions has been lacking.

In this study led by Xianding Deng, PhD, a postdoctoral researcher in the lab of Charles Chiu, MD, PhD, at the University of California, San Francisco, the researchers used a method they had recently developed to assemble viral genomes directly from clinical samples, called Metagenomic Sequencing with Spiked Primer Enrichment (MSSPE), to better understand the nature of SARS-CoV-2 transmission in northern California. MSSPE is used for enriching the viral sequences that is, according to the researchers, “simple, low cost, fast, and deployable on either benchtop or portable nanopore sequencers.”

The team applied MSSPE to positive viral samples recovered from 36 California-based patients. Sequencing the viral genomes and placing them, along with other publicly available genomes, on a phylogenetic tree, revealed that the genomes from northern California were dispersed across the evolutionary tree of SARS-CoV-2; they included lineages circulating in Europe and New York and related to early lineages from China. The virus in California-based travelers on the Grand Princess likely came from Washington State, they noted.

The authors wrote that the phylogenetic analyses “revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities.”

There is growing evidence, the authors noted, that the WA1 strain is now an established lineage of SARS-CoV-2 in the United States. In this study, they found viruses in the WA1 lineage from Grand Princess cruise ship passengers as well as from residents of several northern California counties. In addition, they noted, WA1 lineage viruses have been identified in COVID-19 cases from many states including Minnesota, Connecticut, Utah, Virginia, and New York.

The authors go on to suggest that, based on the current understanding, it is likely that the direction of dissemination “was from Washington State to California and other states.” However, they asserted that this could change in the event that more genomic analysis of strains in the United States end up uncovering more genomic diversity.

Based on their full results, it appears no one virus lineage was predominant in northern California. This suggests that transmission between communities was limited. Instead, virus introductions to the state were likely from people traveling from outside the studied counties and the state.

Despite limitations of their study, including that it represents a relatively sparse sampling of cases, it shows that “robust insights into COVID-19 transmission are achievable if virus genomic diversity is combined and jointly interpreted with detailed epidemiological case data,” the authors said. These results, added the authors, emphasize the need for social distancing and travel restrictions to contain SARS-CoV-2 spread in California and in other states.

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