# Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

“Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients” (2020), by Jérôme Hadjadj et al. Immunology and Microbiology research paper. Original abstract below, unchanged. No free PDF was found.

- Authors: Jérôme Hadjadj, Nader Yatim, Laura Barnabei, Aurélien Corneau, Jérémy Boussier, Hélène Péré, Bruno Charbit, Vincent Bondet, Camille Chenevier‐Gobeaux, Paul Breillat et al.
- Published: July 13, 2020
- Field: Immunology and Microbiology
- DOI: https://doi.org/10.1126/science.abc6027
- Source: https://doi.org/10.1126/science.abc6027

## Abstract

Background Coronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known. Methods We performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy. Results A unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFĸB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines. Conclusion We propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.

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