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In the race against COVID-19 for timely therapeutic developments, mass spectrometry-based high-throughput methods have been valuable. COVID-19 manifests an extremely diverse spectrum of phenotypes from asymptomatic to life-threatening, drastic elevations in immune response or cytokine storm, multiple organ failure and death. These observations warrant a detailed understanding of associated molecular mechanisms to develop therapies. In this direction, high-throughput methods that generate large datasets focusing on changes in protein interactions, lipid metabolism, transcription, and epigenetic regulation of gene expression are extremely beneficial sources of information. Hence, mass spectrometry-based methods have been employed in several studies to detect changes in interactions among host proteins, and between host and viral proteins in COVID-19 patients. The methods have also been used to characterize host and viral proteins, and analyze lipid metabolism in COVID-19 patients. Information obtained using the above methods are complemented by high-throughput analysis of transcriptomic and epigenomic changes associated with COVID-19, coupled with next-generation sequencing. Hence, this review discusses the most recent studies focusing on the methods described above. The results establish the importance of mass spectrometry-based studies towards understanding the infection process, immune imbalance, disease mechanism, and indicate the potential of the methods’ therapeutic developments and biomarker screening against COVID-19 and future outbreaks.

“Multiomics” Approaches to Understand and Treat COVID-19: Mass Spectrometry and Next-Generation Sequencing