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Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients (preprint)
medrxiv; 2020.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2020.04.19.20068015
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 NF{kappa}B. It was also characterized by increased tumor necrosis factor (TNF)- 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- in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Critical Illness
/
COVID-19
/
Necrosis
Language:
English
Year:
2020
Document Type:
Preprint
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