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Critical COVID-19 Unveils the Link between Viral Particle Blood Dissemination and Prolonged Type I Interferon
44 Pages Posted: 8 May 2024
More...Abstract
Background: A significant portion of patients suffering from hypoxemic SARS-CoV-2 pneumonia, insufficiently controlled by early type I interferon (IFN) immunity in respiratory epithelium, experienced a delayed and prolonged IFN response during hospitalization. Employing a comprehensive approach, we aimed to identify host and viral factors associated with severe COVID-19 in subjects with type I IFN response.
Methods: Prospective collection of blood and nasal samples from mild and critical COVID-19 patients allowed us to compare N-antigenemia, humoral immunity, pulmonary and endothelial damage, virological parameters via metagenomics, and innate immune responses through circulating proteins and transcriptomic markers.
Findings: Over 89% of critically-ill patients showed plasma N-protein positivity at ICU admission, with the strongest correlation found between viral particle blood dissemination and a sustained type I IFN response. These results suggest that viral particles may trigger systemic type I IFN responses, potentially explaining delayed responses in critically-ill patients. Using a human primary respiratory epithelium model, we demonstrated that sustained type I IFN pathway activation can disrupt the respiratory epithelium, facilitating the virus's transition from the respiratory compartment to circulation, thereby involving the host in a detrimental cycle.
Interpretation: These findings underscore the critical importance of the timing and duration of type I IFN immunity in COVID-19.
Funding: This study received funding from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS-0154) and to ANR (ANR-RHU Program ANR-21- RHUS-08 (COVIFERON)) through France 2030 program.
Declaration of Interest: MM, VC, LG, AF, SP, GO, and KBP are employees of bioMérieux SA, an in vitro diagnostic company.
Ethical Approval: All participants have been included in clinical studies conducted in Hospices Civils de Lyon, Lyon, France, that complied to French national data protection agency requirements and approved by ethical committees. Written informed consent was obtained from all participants suffering from a mild form of COVID-19 and opposition to use of personal data was sought from the critically-ill patients or their representative in agreement with French regulations.
Keywords: SARS-CoV-2, type I IFN, N-antigenemia, critical illness, innate immune response
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