The COVID-19 pandemic caused by the severe acute respiratory syndrome (SARS)-CoV-2 infection is a systemic disease and a major planetary health burden. While SARS-CoV-2 impacts host biology extensively, our knowledge of these alterations from a systems perspective remains incomplete. Moreover, there is currently only a limited description of this systemic disease. For precision diagnosis and treatment of SARS-CoV-2, multiomics technologies and systems science research offer significant prospects. This expert review offers a critical analysis of the prospects and challenges of the emerging mass spectrometry-based proteomics approaches to the study of COVID-19 as seen through a systems medicine lens. We also discuss the ways in which proteomics is poised to offer hope for diagnostics and therapeutics innovation on SARS-CoV-2 infection as the disease transitions from a pandemic to an endemic disease, and thus further challenging the health systems and services worldwide in the coming decade. Proteomics is an important high-throughput technology platform to achieve a functional overview of the ways in which COVID-19 changes host biology, and hence, can help identify possible points of entry for innovation in medicines and vaccines, among others.
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