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

• Published in: bioRxiv
• Main Authors: Ooi, Amanda, Esau, Luke E., Pugachev, Artyom, Groen, Arnoud, Mfarrej, Sara, Salunke, Rahul P., Subudhi, Amit K., Ben-Rached, Fathia, Alofi, Fadwa, Alsomali, Afrah, Alquthami, Khaled, Khogeer, Asim, Hashem, Anwar M., Almontashiri, Naif, Magistretti, Pierre J., Hala, Sharif, Pain, Arnab
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 10.07.2023
• Edition: 1.1
• Subjects: Immunology; COVID-19 host nasopharynx/ innate immune system/ interferon signaling/ oxidative stress/ retinol metabolism
• ISSN: 2692-8205
• DOI: 10.1101/2023.07.09.548285

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.