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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The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent.
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