Τίτλος:
Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage1,2. Here, we report that for coronavirus disease 2019 (COVID-19) this paradigm does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 moderate-to-severe patients with COVID-19 hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-λ and type I IFN production were both diminished and delayed, induced only in a fraction of patients as they became critically ill. On the contrary, pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-8 were produced before IFNs in all patients and persisted for a prolonged time. This condition was reflected in blood transcriptomes wherein prominent IFN signatures were only seen in critically ill patients who also exhibited augmented inflammation. By comparison, in 16 patients with influenza (flu) hospitalized for pneumonia with similar clinicopathological characteristics to those of COVID-19 and 24 nonhospitalized patients with flu with milder symptoms, IFN-λ and type I IFN were robustly induced earlier, at higher levels and independently of disease severity, whereas pro-inflammatory cytokines were only acutely produced. Notably, higher IFN-λ concentrations in patients with COVID-19 correlated with lower viral load in bronchial aspirates and faster viral clearance and a higher IFN-λ to type I IFN ratio correlated with improved outcome for critically ill patients. Moreover, altered cytokine patterns in patients with COVID-19 correlated with longer hospitalization and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19, contributing to persistent viral presence, hyperinflammation and respiratory failure. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Συγγραφείς:
Galani, I.-E.
Rovina, N.
Lampropoulou, V.
Triantafyllia, V.
Manioudaki, M.
Pavlos, E.
Koukaki, E.
Fragkou, P.C.
Panou, V.
Rapti, V.
Koltsida, O.
Mentis, A.
Koulouris, N.
Tsiodras, S.
Koutsoukou, A.
Andreakos, E.
Περιοδικό:
Nature Immunology
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Λέξεις-κλειδιά:
interferon; interleukin 6; interleukin 8; lambda interferon; transcriptome; tumor necrosis factor; antivirus agent; cytokine; interferon; lambda interferon, adult respiratory distress syndrome; Article; artificial ventilation; bronchial aspiration procedure; clinical article; clinical feature; clinical outcome; cohort analysis; comparative study; computer assisted tomography; controlled study; coronavirus disease 2019; critically ill patient; cytokine production; data analysis software; death; disease severity; female; high throughput sequencing; human; immune response; influenza; Influenza A virus (H1N1); Influenza A virus (H3N2); longitudinal study; male; nasopharyngeal swab; phylogenetic tree; pneumonia; priority journal; respiratory failure; reverse transcription polymerase chain reaction; RNA sequencing; sandwich ELISA; Severe acute respiratory syndrome coronavirus 2; thorax radiography; transcriptomics; viral clearance; virus immunity; virus load; virus pathogenesis; disease exacerbation; gene expression; gene expression profiling; genetics; immunity; immunology; inflammation; influenza; length of stay; metabolism; physiology; procedures; prognosis; virology, Antiviral Agents; COVID-19; Cytokines; Disease Progression; Gene Expression; Gene Expression Profiling; Humans; Immunity; Inflammation; Influenza, Human; Interferon Type I; Interferons; Length of Stay; Prognosis; SARS-CoV-2; Viral Load
DOI:
10.1038/s41590-020-00840-x
