Analysis of Genomic Characteristics and Transmission Routes of Patients With Confirmed SARS-CoV-2 in Southern California During the Early Stage of the US COVID-19 Pandemic

Abstract

Question During the early phase of the outbreak, what were the transmission routes and genomic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in Los Angeles, California? Findings This case series of 192 patients found that 82% of SARS-CoV-2 isolates from Los Angeles shared closest similarity to those originating in Europe vs those from Asia (15%). Using the variation signature of the viral genomes, 2 main clusters were identified, with the top variants sharing genomic features from European SARS-CoV-2 isolates, and several subclusters of SARS-CoV-2 outbreaks represented trackable community spread in Los Angeles. Meaning These findings suggest that SARS-CoV-2 genomes in Los Angeles were predominantly related to the isolates originating from Europe, which are similar to viral strain distributions in New York, New York; a smaller subgroup of SARS-CoV-2 genomes shared similarities to those from originating from Asia, indicating multiple sources of viral introduction within the Los Angeles community. This case series examines the genomic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and transmission routes during the early stages of the coronavirus disease 2019 (COVID-19) outbreak in Los Angeles, California. Importance In late December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. Data on the routes of transmission to Los Angeles, California, the US West Coast epicenter for coronavirus disease 2019 (COVID-19), and subsequent community spread are limited. Objective To determine the transmission routes of SARS-CoV-2 to Southern California and elucidate local community spread within the Los Angeles metropolitan area. Design, Setting, and Participants This case series included 192 consecutive patients with reverse transcription-polymerase chain reaction (RT-PCR) test results positive for SARS-CoV-2 who were evaluated at Cedars-Sinai Medical Center in Los Angeles, California, from March 22 to April 15, 2020. Data analysis was performed from April to May 2020. Main Outcomes and Measures SARS-CoV-2 viral genomes were sequenced. Los Angeles isolates were compared with genomes from global subsampling and from New York, New York; Washington state; and China to determine potential sources of viral dissemination. Demographic data and outcomes were collected. Results The cohort included 192 patients (median [interquartile range] age, 59.5 [43-75] years; 110 [57.3%] men). The genetic characterization of SARS-CoV-2 isolates in the Los Angeles population pinpointed community transmission of 13 patients within a 3.81 km(2)radius. Variation landscapes of this case series also revealed a cluster of 10 patients that contained 5 residents at a skilled nursing facility, 1 resident of a nearby skilled nursing facility, 3 health care workers, and a family member of a resident of one of the skilled nursing facilities. Person-to-person transmission was detected in a cluster of 5 patients who shared the same single-nucleotide variation in their SARS-CoV-2 genomes. High viral genomic diversity was identified: 20 Los Angeles isolates (15.0%) resembled SARS-CoV-2 genomes from Asia, while 109 Los Angeles isolates (82.0%) were similar to isolates originating from Europe. Analysis of other common respiratory viral pathogens did not reveal coinfection in the cohort. Conclusions and Relevance These findings highlight the precision of detecting person-to-person transmission and accurate contact tracing directly through SARS-CoV-2 genome isolation and sequencing. Development and application of phylogenetic analyses from the Los Angeles population established connections between COVID-19 clusters locally and throughout the US.