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

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 km2 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.

Figure 1.. Description of Patient Samples and Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Variations

Orange dots indicate the top 20 altered sites; blue dots, the rest of the variations detected.

Figure 2.. Phylogenetic Tree of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Genomes Sampled From Cedars-Sinai Medical Center Patients in Los Angeles, California, Collected From March 22 to April 15, 2020

Red indicates cluster of patients within the same or adjacent postal codes and the same religious denomination; green, cluster of patients with known close contact transmission event; orange, cluster of residents of a skilled nursing facility, health care workers at the facility, a resident of a nearby facility, and a family member of the facility.

Figure 3.. Phylogenetic Tree With the 6 Most Frequently Altered Sites Observed in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Genomes of Cedar-Sinai Medical Center Samples

Figure 4.. Phylogenetic Tree of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Genomes From Los Angeles, California, and a Global Subsampling