Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, whereas other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed substantially in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help to understand the link between individual clusters and wider community spread.

Highlights d A family of muscle-tropic capsids identified by directed evolution in mice and primates d MyoAAV transduction is dependent on integrin heterodimers in mouse and human cells d MyoAAV administration at low dose results in therapeutic efficacy in disease models d Systemically administrated MyoAAV transduces primate muscles highly efficiently

Eicosanoids and related species are critical, small bioactive mediators of human physiology and inflammation. While ~1100 distinct eicosanoids have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of eicosanoids and their role in human biology. Using a directed non-targeted mass spectrometry approach in conjunction with computational chemical networking of spectral fragmentation patterns, we find over 500 discrete chemical signals highly consistent with known and putative eicosanoids in human plasma, including 46 putative novel molecules not previously described, thereby greatly expanding the breath of prior analytical strategies. In plasma samples from 1500 individuals, we find members of this expanded eicosanoid library hold close association with markers of inflammation, as well as clinical characteristics linked with inflammation, including advancing age and obesity. These experimental and computational approaches enable discovery of new chemical entities and will shed important insight into the role of bioactive molecules in human disease.