Type I Interferons in COVID-19 Pathogenesis

Palermo, Enrico; Carlo, Daniele Di; Sgarbanti, Marco; Hiscott, John

doi:10.3390/biology10090829

Cited by 38 publications

(24 citation statements)

References 99 publications

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“…A highly impaired IFN‐I response is known to underlie severe COVID‐19 [1–3]. In a subset of COVID‐19 patients, the defect is explained by the presence of auto‐Abs against IFN‐I [8, 10–12].…”

Section: Discussionmentioning

confidence: 99%

Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

et al. 2022

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A significant number of COVID‐19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN‐α/‐β were screened in COVID‐19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN‐α/‐β/‐ω, using an antiviral bioassay. Transcript levels of IFN‐α/‐β/‐ω and IFN‐stimulated genes (ISGs) were quantified. Anti‐IFN‐I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN‐α. A total of 69.2% of anti‐IFN‐α NAB sera displayed cross‐reactivity to IFN‐ω. Anti‐IFN‐I NAB persisted in all patients. NAB to IFN‐α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti‐IFN‐I NAB were higher in males ( p = 0.0017), patients admitted to the ICU ( p < 0.0001), and patients with a fatal outcome ( p < 0.0001). NAB were associated with higher levels of CRP, LDH, d ‐Dimer, and higher counts of hematological parameters. ISG‐mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID‐19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.

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Section: Discussionmentioning

confidence: 99%

Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

et al. 2022

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“…However, IFNs show differential associations with clinical markers of poor prognosis and COVID-19 severity (38). Regarding IFN-I's role in COVID-19, it was demonstrated that numerous SARS-CoV-2 proteins have the ability to inhibit IFN-I production and/or IFN-I responses (39), producing resistance to this antiviral mechanism (40). Although viruses display strategies to evade the IFN antiviral activity, there are host-factors that affect the severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Pin-pointing the key hubs in the IFN-γ pathway responding to SARS-CoV-2 infection

Toro

Lage-Vickers

Bizzotto

et al. 2022

Preprint

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Interferon gamma may be a potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-gamma pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2 positive and negative patients, we identified IFN-gamma-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1 and JAK2 in COVID-19 positive vs. negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15 and OAS1 (4 well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19 positive vs. negative patients. Integrative analyses showcased higher levels of ISGs which were associated with increased viral load and STAT1/JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly(I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-gamma and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.

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“…Recently, it has been demonstrated that insufficient antiviral IFN-I responses are the hallmark of COVID-19 infection ( Lin and Shen, 2020 ). Several SARS-CoV-2 proteins, including nucleocapsid (N), membranous (M), and nonstructural (NS) proteins, inhibit the production of IFN-Is ( Palermo et al, 2021 ). On the other hand, the result of multiplexed single-cell epitope and transcriptome sequencing revealed the dysfunction of ISG responses in patients with severe COVID-19 ( van der Wijst et al, 2021 ).…”

Section: Anti–ifn–i Autoantibody In Covid-19: Immunopathogenesis and ...mentioning

confidence: 99%

Type-I interferons in the immunopathogenesis and treatment of Coronavirus disease 2019

Khorramdelazad

Kazemi

Azimi

et al. 2022

European Journal of Pharmacology

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Type I Interferons in COVID-19 Pathogenesis

Cited by 38 publications

References 99 publications

Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

Pin-pointing the key hubs in the IFN-γ pathway responding to SARS-CoV-2 infection

Type-I interferons in the immunopathogenesis and treatment of Coronavirus disease 2019

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