Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID.

Autor:	Biondi MJ; School of Nursing, York University, Toronto, ON M3J 1P3, Canada.; Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada., Addo M; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada., Zahoor MA; Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada., Salvant E; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada., Yip P; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.; Precision Diagnostics and Therapeutics Program, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada., Barber B; Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada., Smookler D; Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada., Wasif S; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada., Gaete K; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada., Kandel C; Michael Garron Hospital, Toronto, ON M4C 3E7, Canada., Feld JJ; Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada., Tsui H; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.; Precision Diagnostics and Therapeutics Program, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada., Kozak RA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Jazyk:	angličtina
Zdroj:	Pathogens (Basel, Switzerland) [Pathogens] 2024 Jun 17; Vol. 13 (6). Date of Electronic Publication: 2024 Jun 17.
DOI:	10.3390/pathogens13060510
Abstrakt:	Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu