SARS-CoV-2 Genomic Variation in Space and Time in Hospitalized Patients in Philadelphia

Everett, John; Hokama, Pascha; Roche, Aoife M.; Reddy, Shantan; Hwang, Young; Kessler, Lyanna; Glascock, Abigail; Li, Yize; Whelan, Jillian N.; Weiss, Susan R.; Sherrill-Mix, Scott; McCormick, Kevin; Whiteside, Samantha A.; Graham-Wooten, Jevon; Khatib, Layla A.; Fitzgerald, Ayannah S.; Collman, Ronald G.; Bushman, Frederic

The severe acute respiratory coronavirus 2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. The epidemic accelerated in Philadelphia, PA, in the spring of 2020, with the city experiencing a first peak of infections on 15 April, followed by a decline through midsummer. Here, we investigate spread of the epidemic in the first wave in Philadelphia using full-genome sequencing of 52 SARS-CoV-2 samples obtained from 27 hospitalized patients collected between 30 March and 17 July 2020. Sequences most commonly resembled lineages circulating at earlier times in New York, suggesting transmission primarily from this location, though a minority of Philadelphia genomes matched sequences from other sites, suggesting additional introductions. Multiple genomes showed even closer matches to other Philadelphia isolates, suggestive of ongoing transmission within Philadelphia. We found that all of our isolates contained the D614G substitution in the viral spike and belong to lineages variously designated B.1, Nextstrain clade 20A or 20C, and GISAID clade G or GH. There were no viral sequence polymorphisms detectably associated with disease outcome. For some patients, genome sequences were determined longitudinally or concurrently from multiple body sites. In both cases, some comparisons showed reproducible polymorphisms, suggesting initial seeding with multiple variants and/or accumulation of polymorphisms after infection. These results thus provide data on the sources of SARS-CoV-2 infection in Philadelphia and begin to explore the dynamics within hospitalized patients.