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bioRxiv · 10.1101/2023.07.09.548285

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.
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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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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. Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severity. https://doi.org/10.1101/2023.07.09.548285

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