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Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severity

Ooi, A.; Esau, L. E.; Pugachev, A.; Groen, A.; Sara Mfarrej, R.; Salunke, R. P.; Subudhi, A. K.; Ben-Rached, F.; Alofi, F.; Alsomali, A.; Khogeer, A.; Hashem, A. M.; Almontashiri, N.; Magistretti, P. J.; Hala, S.; Pain, A.

2023-07-10 immunology
10.1101/2023.07.09.548285 bioRxiv
Show abstract

An aberrant innate immune system caused by the beta coronavirus SARS-CoV-2 is a characteristic manifestation of severe coronavirus disease 2019 (COVID-19). Here, we performed proteome profiling of nasopharyngeal (NP) swabs from 273 hospitalized patients with mild and severe COVID-19 symptoms, including non-survivors. We identified depletion in STAT1-mediated type I interferon response, retinol metabolism and NRF2 antioxidant system that are associated with disease severity in our patient demography. We found that the dysregulation of glucocorticoid signaling and renin-angiotensin-aldosterone system (RAAS) contribute to the pathophysiology of COVID-19 fatality. Hyperactivation of host innate immune system was observed in severe patients, marked by elevated proteins involved in neutrophil degranulation and platelet aggregation. Our study using high-throughput proteomics on the nasopharynx of COVID-19 patients provides additional evidence on the SARS-CoV-2-induced pathophysiological signatures of disease severity and fatality.

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