Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection has become a global health pandemic. COVID-19 severity ranges from asymptomatic infection to severe multi-organ disease. Although the inflammatory response has been implicated in the pathogenesis of COVID-19, the exact nature of dysregulation in signaling pathways has not yet been elucidated underscoring the need for further molecular characterization of SARS-CoV-2 infection in humans. Here, we characterize the host response directly at the point of viral entry through analysis of nasopharyngeal swabs. Multiplexed high resolution mass spectrometry-based proteomic analysis of confirmed COVID-19 cases and negative controls identified 7,582 proteins and revealed significant upregulation of interferon-mediated antiviral signaling in addition to multiple other proteins that are not encoded by interferon-stimulated genes (ISGs) or well-characterized during viral infections. Downregulation of several proteasomal subunits, E3 ubiquitin ligases, and components of protein synthesis machinery was significant upon SARS-CoV-2 infection. Targeted proteomics to measure abundance levels of MX1, ISG15, Stat1, RIG-I and CXCL10, detected proteomic signatures of interferon-mediated anti-viral signaling that differentiated COVID-19 positive from negative cases. Phosphoproteomic analysis revealed increased phosphorylation of several proteins with known antiviral properties as well as several proteins involved in ciliary function (CEP131 and CFAP57) that have not previously been implicated in the context of coronavirus infections. Additionally, decreased phosphorylation levels of AKT and PKC, which have been shown to play varying roles in different viral infections, were observed in infected individuals relative to controls. These data provide novel insights that add depth to our understanding of SARS-CoV-2 infection in the upper airway and establish a proteomic signature for this viral infection.

Several plasma glycoproteins are clinically useful as biomarkers in a variety of diseases. Although thousands of proteins are present in plasma, >95% of the plasma proteome by mass is represented...

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We present optimized settings for ramp times and ion mobility range in trapped ion mobility spectrometry experiments involving single cell analysis.