New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID-19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

A B S T R A C T PurposeTo define a gene expression profile of BRCAness that correlates with chemotherapy response and outcome in epithelial ovarian cancer (EOC). MethodsA publicly available microarray data set including 61 patients with EOC with either sporadic disease or BRCA1/2 germline mutations was used for development of the BRCAness profile. Correlation with platinum responsiveness was assessed in platinum-sensitive and platinum-resistant tumor biopsy specimens from six patients with BRCA germline mutations. Association with poly-ADP ribose polymerase (PARP) inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones. The BRCAness profile was validated in 70 patients enriched for sporadic disease to assess its association with outcome. ResultsThe BRCAness profile accurately predicted platinum responsiveness and mutation status in eight of 10 patient-derived tumor specimens and between PARP-inhibitor sensitivity and resistance in four of four Capan-1 clones. When applied to the 70 patients with sporadic disease, patients with the BRCA-like (BL) profile had improved disease-free survival (34 months v 15 months; log-rank P ϭ .013) and overall survival (72 months v 41 months; log-rank P ϭ .006) compared with patients with a non-BRCA-like (NBL) profile, respectively. The BRCAness profile maintained independent prognostic value in multivariate analysis, which controlled for other known clinical prognostic factors. ConclusionThe BRCAness profile correlates with responsiveness to platinum and PARP inhibitors and identifies a subset of sporadic patients with improved outcome. Additional evaluation of this profile as a predictive tool in patients with sporadic EOC is warranted.