The first COVID-19 case was identified in New York City on February 29. Since then, the city has been considered one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, a team from the Icahn School of Medicine at Mount Sinai sequenced SARS-CoV-2 strains from 84 patients seeking care within their health care system. Their phylogenetic analysis found that the first confirmed COVID-19 cases arose mostly through untracked transmission of the virus from Europe and other parts of the United States.

The team’s research is published in Science in the paper, “Introductions and early spread of SARS-CoV-2 in the New York City area.”

Ana S. Gonzalez-Reiche, PhD, post-doc at the Icahn School of Medicine at Mount Sinai and first author on the paper, used SARS-CoV-2 sequences collected at the Mount Sinai Health System through March 18, from patients representing 21 New York City neighborhoods and two towns in neighboring Westchester County. The authors sequenced 90 SARS-CoV-2 genomes from 84 confirmed COVID-19 positive cases and analyzed these sequences together with all publicly available SARS-CoV-2 genomes from around the world (more than 2,000).

The results indicate SARS-CoV-2 was introduced to New York City through multiple independent but isolated introductions mainly from Europe and other parts of the United States. Most of these cases appear associated with untracked transmission and potential travel-related exposures, the authors said. Very few of the cases were infected with a virus that looked to be introduced from Asia, and in those, the virus was most closely related to viral isolates from Seattle, WA.

The authors also found evidence that early spread of the virus in New York City was sustained by community transmission as suggested by clusters of related viruses found in patients living in different neighborhoods of the city. They identified two clusters totaling 21 closely related cases. One cluster, the authors noted, included 23% of the isolates contained in one clade and 20% of the total isolates sequenced. Based on zip code information, they suggested, the cases from this cluster “were distributed across five counties”—including one sample from New Rochelle which is part of the metropolitan area directly north of NYC and reported the first documented cluster of community-acquired infections in NY state on March 3, 2020. This cluster, they explained, is characterized by a particular amino acid substitution A1844V in the ORF1b gene. Basal to these clusters are isolates from the states of MN, WA, and CA. The relatedness of other U.S. and NY isolates suggests that the viruses spreading locally could have been introduced to NY through a domestic route.

The second cluster was a smaller group that contained four isolates from Manhattan and one isolate from Queens. Zip code information was available for three of the Manhattan cases, noted the authors. This information was used to map the cases to three different neighborhoods—lending more support to the hypothesis of community spread. Although most NYC cases are intermixed within this largely European clade, noted the authors, these results suggest that domestic introductions may have also been a source of early community spread within NYC.

These observations are also supported by the city-wide distribution of these cases, which mapped to three of four represented NYC boroughs and five NY state counties.

The data also point to the limited efficacy of travel restrictions in a place once multiple introductions of the virus and community-driven transmission have already occurred. The results also underscore the need for early and continued broad testing to identify untracked transmission clusters in communities.

The team took advantage of an existing infrastructure to investigate the origins of SARS-CoV-2 strains circulating in NYC and to dissect the spread of the virus in this metropolitan area. First, there are thousands of SARS-CoV-2 sequences collected at www.gisaid.org by researchers around the globe. In addition, the Pathogen Surveillance Program (PSP) at the Icahn School of Medicine at Mount Sinai is a multidisciplinary, institutional infrastructure which seeks to generate high resolution, near real-time genetic information on pathogens found to cause disease in the large and diverse patient population seeking care at the Mount Sinai Health System in NYC. Some of the methods employed are biospecimen coding, nucleic acid extraction and qPCR quantification, and next-generation sequencing approaches based on Illumina and Pacific Biosciences technology.