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

Abstract

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. IMPORTANCE Understanding how SARS-CoV-2 spreads globally and within infected individuals is critical to the development of mitigation strategies. We found that most lineages in Philadelphia had resembled sequences from New York, suggesting infection primarily but not exclusively from this location. Many genomes had even nearer neighbors within Philadelphia, indicating local spread. Multiple genome sequences were available for some subjects and in a subset of cases could be shown to differ between time points and body sites within an individual, indicating heterogeneous viral populations within individuals and raising questions on the mechanisms responsible. There was no evidence that different lineages were associated with different outcomes in patients, emphasizing the importance of individual-specific vulnerability.

Signatures of COVID-19 Severity and Immune Response in the Respiratory Tract Microbiome

“…There was no association between SARS-CoV-2 RNA levels and WHO score or clinical outcomes (Wilcoxon rank sum test). Complete SARS-CoV-2 genome sequences were determined for 26 subjects as recently reported ( 20 ). All viral genomes were members of the B.1 lineage, which encodes the D614G variant in spike, and most also had the P314L variant in the RNA-dependent RNA polymerase (RdRp) located on ORF1b ( 21 , 22 ).…”

“…Oropharyngeal (OP) and nasopharyngeal (NP) swabs, and endotracheal aspirates (ETA) from intubated subjects, were obtained as previously described ( 18 ). Additional OP and NP swabs were obtained and eluted in viral transport medium (VTM) for SARS-CoV-2 analysis as previously described ( 20 ). COVID-19 patients were classified clinically by maximum score reached during hospitalization using the 11-point WHO COVID-19 progression scale ( 16 ).…”

Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review

“…The first three cases (20–1891820–1930320–19305) are classified as "S" type for the Chilean strains. Meanwhile, the fourth case (20–19731) is a "G" type, according to nucleotide substitutions in the positions 28 144 and 23 403 11 Everett [ 30 ] Research article USA COIVD-19 patients D614G, RNA-dependent RNA polymerase (RdRp) located on ORF1b The D614G substitution has been proposed to promote infection of human cells, and this variant has spread globally at the expense of other genotypes 12 Forni [ 31 ] Original article Italy SARS-CoV-2 genomes D614G Recent studies have indicated that the D614G variant, which is now prevalent worldwide, enhances viral infectivity 13 Forster [ 32 ] Research article Germany COVID-19 patients Three central variants: A variant B variant C variant Node B is derived from A by two mutations: the synonymous mutation T8782C and the non-synonymous mutation C28144T changing a leucine to a serine. Type C differs from its parent type B by the non-synonymous mutation G26144T, which changes a glycine to a valine 14 Gómez-Carballa [ 33 ] Research article Spain SARS-CoV-2 genomes C8782T, C18060T, T28144C, C29095T Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to sub-clade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe 15 Goren [ 34 ] Letter to the editor USA COIVD-19 patients TMPRSS2 Both SARS-CoV-2 and influenza are dependent on TMPRSS2 for infectivity, it is likely that SARS-CoV-2 will have a similar seasonal cycle; thus, the fall and winter are likely to see an increase in COVID-19 cases 16 Graudenzi [ 35 ] Research ...…”

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

“…A total of 45 articles addressed the effect of viral mutations on severity of COVID-19 in patients, of which fifteen studies (five bigdata analyses [21,30,33,34,40] and ten clinical studies [39,[41][42][43][44][45][46][47][48][49]) showed no association between SARS-CoV-2 variants and severity of disease. Three studies (one bigdata analysis [50] and two clinical studies [17,51]) reported that the SARS-CoV-2 variants were significantly associated with decrease in severity of disease.…”