key: cord-0802098-wabruzfs
authors: Gu, Wei; Deng, Xianding; Reyes, Kevin; Hsu, Elaine; Wang, Candace; Sotomayor-Gonzalez, Alicia; Federman, Scot; Bushnell, Brian; Miller, Steve; Chiu, Charles
title: Associations of Early COVID-19 Cases in San Francisco with Domestic and International Travel
date: 2020-05-21
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa599
sha: 8aed4c667874cdd1cde6d6c254f6dcfbc90a4a5c
doc_id: 802098
cord_uid: wabruzfs

In early-to-mid March 2020, 20 of 46 (43%) COVID-19 cases at a tertiary care hospital in San Francisco, California were travel-related. Cases were significantly associated with travel to Europe or New York (odds ratio 32.9). Viral genomes recovered from 9 of 12 (75%) cases co-clustered with lineages circulating in Europe.

M a n u s c r i p t

As of April 4 th , 2020, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus 1 , has infected more than 1.2 million people worldwide and the rise in cases has been exponential. In particular, New York cases in the United States quickly surged from 22 to >10,000 between March 10 and 22 2 . By April 4 th there are >150,000 cases in New York and nearby New Jersey, threatening to overwhelm hospitals and other regional health care systems in the city.

In San Francisco, we validated a qRT-PCR test to detect SARS-CoV-2 infection from nasopharyngeal swab samples based on the EUA (Emergency Use Authorization)approved US CDC assay 3 . During the first 10 days since launch, we performed SARS-CoV-2 testing on 947 samples collected from March 10 through March 20 from patients with suspected SARS-CoV-2 infection at University of California, San Francisco. We reviewed the electronic medical records from the first 46 consecutive SARS-CoV-2 positive cases admitted to University of California, San Francisco hospitals or seen in outpatient clinics from March 10 through March 20. Data from these COVID-19 patients were matched with 102 randomly selected negative controls who were patients who tested negative for SARS-CoV-2 over the same time period. Documented history was recorded by a physician or nurse practitioner and included sick contacts, health care worker status, and travel history. Among the 46 COVID-19 positive patients, the median age was 44 years, 46% were female, and 65% were outpatients (Table S1) .

We noted that a travel history within 2 weeks of symptom onset (median date Mar 11, 2020) Table S2 , S3). The association with travel may be due to direct exposure to SARS-CoV-2 while in high prevalence regions (e.g. NY) or exposure while traveling (close contact with fellow travelers or airport personnel). One cluster of 3 positive cases associated with COVID-19 infection in an airport worker was categorized as a case of community rather than travel-associated transmission. No significant associations were found with regards to close contacts with known COVID-19 infected persons or frontline healthcare workers. Those who did not have a recent travel history, a close contact who was COVID-19 positive, or were not a frontline healthcare worker were categorized as community transmission with an unknown source of infection and comprised 39% of cases.

We conducted viral genomic sequencing and phylogenetic analysis of SARS-CoV-2 viruses from 12 of 20 travelers for whom the breadth of coverage of the viral genome was >90% 4-6 . These viral genomes were aligned using MAFFT v7.427 7 with 762 high-coverage viral genomes deposited in the GISAID database 8, 9 as of March 20, 2020, in addition to the most recent viral genomes sequenced in California as of May 3, 2020 4 , for a total of 983 sequences. A maximum likelihood phylogenetic tree was constructed using IQTREE (version 2) using an HKY substitution model 10 ( Figure 2 ).

We defined genomic clades through the GISAID nomenclature found at that point in time on March 20, 2020 8, 9 . The majority (9 of 12) of all travel cases clustered in the G A c c e p t e d M a n u s c r i p t clade as defined by the spike protein D614G variant marker (Figure 2 , S1, S2), including 3 cases from Europe (UC40, UC45, UC46), 4 cases from New York (UC27, UC36, UC44, UC47), 1 case from Los Angeles (UC26), and 1 case from Chicago (UC48). Viruses in the G clade comprise most of the genomes sequenced from patients in Europe 8, 9 , but notably have also been identified in the vast majority of cases associated with the New York SARS-CoV-2 outbreak in March to April of 2020, which occurred after the timeline of this study 11, 12 Viruses from two additional travel-associated cases from Europe (UC43) and New York (UC41) were mapped to other clades circulating in Europe (Figure 2) . The additional case from Europe was found to be part of the V clade, defined by a G251V mutation in the NS3 protein 8,9 . Limitations of our study include the use of epidemiological data from only the first 10 days of testing at a single institution. Nevertheless, in the setting of an emergent pandemic with shifting epidemiology, the results of our study reached statistical significance over 4 categories of travel (all travel, New York, USA, and Europe), and yielded data that may have presaged the exponential rise of New York cases and subsequent large-scale outbreak in the New York metropolitan area 11,12 . A c c e p t e d M a n u s c r i p t 

M a n u s c r i p t 

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A c c e p t e d M a n u s c r i p t