Determining factors of transmission and evolution of SARS-CoV-2 in populations at risk

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The major aspects of this project involve characterizing SARS-CoV-2 genetic diversity and microbial communities in the respiratory tract during infection. This involves analyzing samples from cell culture experiments, from COVI19 positive subjects, and from model animal infections. One of our studies under this project aims to identify sequence heterogeneity in low-passage SARS-CoV-2 isolates and sequence plaque-purified Vero E6-grown variants provided by our collaborator, Prof. Meike Dittman (NYU Langone) who has observed that passaged strains grow in plaques of different sizes, indicating a mixture of different variants. We are characterizing phenotypic differences between the Wuhan (USA/WA1/2020) strain and the D614G lineage (USA/NYU-VC-003/2020) in vitro and determining the phenotypic consequences of the loss of the furin site. In a separate study we are examining SARS-CoV-2 virus genetic diversity over the course of the infection in human subjects and in an obese ferret model. This diet induced obesity (DIO) model of obesity was developed by collaborator Dr. Stacey Schultz-Cherry, who will provide tissue for analysis. We will extract total RNA from nasal washes and respiratory tract tissues collected from lean and obese ferrets over the course of the infection (multiple timepoints). Analyses will involve viral RNAseq, mRNAseq from blood, as well as glycomic profiling to provide a systems level picture of the infected host. A comparative analysis to human infections will be done with the concurrent analysis of the virus from nasopharyngeal (NP) swabs, and from bronchoalveolar lavages from hospitalized subjects with COVID19. We are analyzing the BAL from 145 hospitalized patients with COVID19 by metagenomics and metatranscriptomics to do a functional profiling of the microbiome and virome as a function of outcomes.