Abstract
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. To determine the transmission routes of SARS-CoV-2 to Southern California and elucidate local community spread within the Los Angeles metropolitan area. 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. 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. 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. 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.
Highlights
The emergence of the coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1] presents the scientific community with an urgent need to understand all aspects of this novel virus
2 of our highly altered sites, G25563T(ORF3a) and C1059T(nsp2), have been reported exclusively in US isolated sequences collected since March 2020,7 a timeline that corresponds to this study’s sample collection date. These variants were found to be closely associated within a cluster containing mainly SARS-CoV-2 genomes from New York, suggesting that these genomes were introduced from a strain that emerged from the US East Coast population
From the variants found in our samples, 4 variants, 5′-UTR (241C>T), 3037C>T, 14408C>T, and 23403A>G, agree with other studies that found that these variations coevolved.[37]. Such a high proportion of our patients having all 4 variation indicates the seeding of our population by a strain originating in Europe. This finding is further validated in our local phylogenetic tree, which separates into 2 main clusters, our global tree in which our population closely resembles SARSCoV-2 genomes from New York,[9] followed by a smaller percentage from Washington state, together identifying possible routes for the dissemination of SARS-CoV-2 into the Southern California populace
Summary
The emergence of the coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1] presents the scientific community with an urgent need to understand all aspects of this novel virus. The SARS-CoV-2 genome sequences deposited in public databases[2,3] are pivotal resources in understanding its virulence and for guiding approaches to therapeutics and vaccines.[4] Assessing core genomic features across all global populations can be used for comparative analysis to identify features unique to SARS-CoV-2 as well as assist in epidemiologic and public health endeavors.[2,5,6,7,8,9,10,11,12,13,14,15]. Clade 20B was seeded by a strain from China, but once in Europe, its variation profile became the predominant strain of the European pandemic.[19]
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