Title: Insights from a longitudinal SARS-CoV-2 multi-omic study
Abstract: Since early 2020, SARS-CoV-2 has drastically changed the world around us and raised seemingly endless scientific questions about its mechanisms, effects, and diagnostics. Through a collaboration with Mt. Sinai and the U.S. Marine Corps, we leveraged a unique prospective cohort with symptom reporting, serology, viral load measurements, transcriptomic, and proteomic data to study several aspects of infection. We tracked the profiles of inflammatory proteins in the blood throughout infection, comparing asymptomatic cases with participants who experienced symptoms to identify specific proteins that may repress symptoms. We studied sex differences in symptoms, viral load, blood transcriptome, RNA splicing, and proteomic signatures, which indicated that the antiviral innate immunity set point causally contributes to sex differences in response to SARS-CoV-2 infection. We also discovered a host-based alternative splicing signature that, as the basis of a machine learning diagnostic model, had near-perfect diagnostic accuracy and identified cases of false negative PCR tests. Taken together, this work addressed many key questions about SARS-CoV-2 infection, and suggests even more avenues for follow-up and future stud