Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread

Moustafa, Ahmed; Planet, Paul J.

doi:10.1101/2020.06.08.139055

Cited by 5 publications

(14 citation statements)

References 25 publications

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“…However, despite our earlier estimates, an even larger portion of our sample population had a significant resemblance to genomes from New York, the epicenter of the SARS-CoV-2 outbreak in the US. 9,12,44 The appearance of the majority of our samples within different subclades of New York isolates suggests that SARS-CoV-2 likely spread from multiple introductions from New York. Furthermore, the CSMC population interspersed with Washington state and China isolates suggests multiple dissemination routes from Asia and the US Northern West Coast to Southern California, appearing as a major cluster in our local population.…”

Section: Discussionmentioning

confidence: 93%

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

et al. 2020

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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-toperson 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.

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Section: Discussionmentioning

confidence: 93%

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

et al. 2020

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“…All SARS-CoV-2 genomes (n=169)[13] were queried against the GNUVID database (version August 17 th 2020) that has 32,719 high coverage complete genomes[8, 12]. Each genome was assigned an ST profile and CC.…”

Section: Methodsmentioning

confidence: 99%

“…Each genome was assigned an ST profile and CC. A minimum spanning tree (MST) was then constructed using the goeBURST algorithm[15, 16] to group STs into larger taxonomic units, clonal complexes (CCs), which we define as clusters of >20 STs that are single or double allele variants away from a “founder”[8, 17]. Temporal plots were extracted using a custom script and plotted in GraphPad Prism v7.0a.…”

Section: Methodsmentioning

confidence: 99%

“…Eighty-three samples were from patients less than 21 years old. We used our genotyping tool GNUVID[8] to classify and compare these strains to the growing global database of SARS-CoV-2 sequences at GISAID[12] (Supplementary Table 1)[13]. Here we show that the early pandemic and peak in Philadelphia were characterized by multiple, diverse, circulating viral variants, especially amongst children.…”

Section: Introductionmentioning

confidence: 98%

“…After an initial period in January 2020 when most severe acute respiratory coronavirus 2 (SARS-CoV-2) infections in the US were travel-related, the virus quickly established itself during February with sustained, community spread[1]. Studies tracking the spread of the virus using whole genome phylogenetics suggested multiple introductions during this time period from Europe and Asia [2-7], as well as multiple waves of transmission of distinct variants that differ locally[8].…”

Section: Introductionmentioning

confidence: 99%

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Early pandemic molecular diversity of SARS-CoV-2 in children

Moustafa

Otto

Gai

et al. 2021

Preprint

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Background In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children's Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus. Methods We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences. We used genotyping tools to track variants over time and to test for possible genotype associated clinical presentations and outcomes in children. Results Our analysis uncovered 13 major lineages that changed in relative abundance as cases peaked in mid-April in Philadelphia. We detected at least 6 introductions of distinct viral variants into the population. As a group, children had more diverse virus genotypes than the adults tested. No strong differences in clinical variables were associated with genotypes. Conclusions Whole genome analysis revealed unexpected diversity, and distinct circulating viral variants within the initial peak of cases in Philadelphia. Most introductions appeared to be local from nearby states. Although limited by sample size, we found no evidence that different genotypes had different clinical impacts in children in this study.

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Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic

Zhang

Govindavari

Davis

et al. 2020

Preprint

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Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5′UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10 percent of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50 percent of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.

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Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread

Cited by 5 publications

References 25 publications

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

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

Early pandemic molecular diversity of SARS-CoV-2 in children

Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic

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