Benjamin Terrier - August 12, 2020

Benjamin Terrier, PhD, Professeur des Universités-Praticien Hospitalier, Université de Paris, Service de Médecine Interne, Hôpital Cochin, "Impaired type 1 interferon activity and exacerbated inflammatory responses in severe Covid-19"

Professor Benjamin Terrier presents the results from a recently published study of interferon response in 50 Covid-19 patients. The study was motivated by the hypothesis that interferon responses cause hyperinflation during the worsening of disease progression 9-12 days after the onset of symptoms. The authors collected clinical and biological data of patients with mild, severe and critical Covid-19, including in-depth phenotypic analysis of immune cells, whole blood transcriptomic analysis and cytokine measurements. This data was compared to data from 18 healthy controls that tested negative for the virus and were matched for age and gender.

Using t-SNE to visualize cell density (viSNE), they found that more severe cases had a decrease in the density of NK (natural killer) cells and CD3+ T cells, and an increase in the density of B cells and monocytes. They then did an Nanostring nCounter immunology panel to identify differentially expressed genes as a function of severity grades. PCA analysis revealed that the expression of genes going down involved interferons IFNS-I/II signaling. Multiplex gene expression analysis showed an up-regulation of genes involved in type I IFN signaling, and a down-regulation of interferon stimulated genes (ISGs) in critical patients. Interestingly, IFN-β was undetectable in all patients. Overall, these data suggested that patients with severe and critical covid-19 have an impaired type I IFN production and a lower viral clearance, high blood viral load and an excessive NF0κB driven inflammatory response associated with increased TNF-α and IL-6.

The study then looked into the predictive power of these results, and found that low type I IFN response indeed preceded clinical deterioration to critical status, and that cytokine and chemokine related genes were increasingly expressed as a function of disease severity. The study thus concluded that type I IFN deficiency is a hallmark of severe Covid-19. Finally, the authors suggested that severe and critical Covid-19 patients might be potentially relieved from the IFN deficiency by IFN administration from exacerbated inflammation by adapted anti-inflammatory therapies.

Interestingly, this matches nicely with work from the TenOever lab, which found that Covid-19 infection induces low levels of specific interferons IFN-I and IFN-III in cell/animal models. Professor Benjamin TenOever discussed his work at the COVID-19 Virtual Symposium on June 3 here: https://research.columbia.edu/covid/s...

The article was recently published in Science here: https://science.sciencemag.org/conten..., and can also be found on medRxiv here: https://www.medrxiv.org/content/medrx...