Typeinterferon deficiency: Biomarker of patients at risk of severe
COVID-19

Date:
July 17, 2020
Source:
INSERM (Institut national de la sante' et de la recherche me'dicale)
Summary:
Which patients are more likely to develop a severe form of
COVID-19? In a new study, researchers describe a unique and
unexpected immunological phenotype in severe and critical patients.



FULL STORY ========================================================================== Which patients will develop a severe form of Covid-19? This is a key
question that needs to be answered to improve the individual management
and prognosis of patients. In a study published in Science on July 13,
teams from AP-HP, Inserm, Universite' of Paris, Institut Pasteur and
Institut Imagine describe a unique and unexpected immunological phenotype
in severe and critical patients, consisting of a severely impaired
response of interferon (IFN) type I, associated with a persistent blood
viral load and an excessive inflammatory response. These data suggest
that IFN type I deficiency in the blood could be a hallmark of severe
forms of Covid-19. It also supports the potential value of therapeutic approaches that combine early administration of IFN, with appropriate anti-inflammatory therapy targeting IL-6 or TNF-a, in patients preventing severe disease forms.


========================================================================== Approximately 5% of people with Covid-19 progress to a severe or critical
form, including the development of severe pneumonia that progresses to
acute respiratory distress syndrome. While these forms sometimes occur
early in the course of the disease, clinical observations generally
describe a two-stage progression of the disease, beginning with a mild
to moderate form, followed by respiratory aggravation 9 to 12 days after
the onset of the first symptoms.

This sudden progression suggests deregulation of the host inflammatory response.

A growing number of indications suggest that this aggravation is caused
by a large increase in cytokines. This runaway inflammatory response
is correlated with massive infiltration in the lungs of innate immune
cells, namely neutrophils and monocytes, creating lung damage and acute respiratory distress syndrome.

By analogy with a genetic disease leading to a similar pulmonary pathology identified at Institut Imagine by the team of Inserm researcher Fre'de'ric Rieux-Laucat, the initial hypothesis assumed excessive production of
interferon (IFN) type I, a marker of the response to infections. However,
in seriously ill patients, the teams of Darragh Duffy (Dendritic Cell Immunobiology Unit, Institut Pasteur/Inserm), Fre'de'ric Rieux-Laucat (Laboratory of Immunogenetics of Pediatric Autoimmune Diseases at
Institut Imagine -- Inserm/Universite' de Paris), Solen Kerne'is (Mobile Infectiology Team, AP-HP. Centre -- Universite' of Paris) and Benjamin
Terrier (Department of Internal Medicine, AP-HP. Centre -- Universite'
of Paris) show that the production and activity of type-I IFN are strongly reduced in the most severe forms of Covid-19.

In addition, there is a persistent blood viral load, indicating poor
control of viral replication by the patient's immune system which
leads to an ineffective and pathological inflammatory response. The inflammation, caused by the transcription factor NF-kB, also leads to
increased production and signaling of tumor necrosis factor (TNF)-alpha
and the pro-inflammatory cytokine interleukin IL-6.

Distinct type-I IFN responses may be characteristic of each stage of
the disease This low signature of type-I IFN differs from the response
induced by other respiratory viruses such as human respiratory syncitial
virus or influenza A virus, both of which are characterized by high
production of type-I IFN.

The study also showed that low levels of type-I IFN in plasma precede
clinical worsening and transfer to intensive care. Levels of circulating
Type 1 IFN could even characterize each stage of disease, with the lowest levels observed in the most severe patients. These results suggest that
in SARS-CoV- 2 infection, the production of type-I IFN is inhibited in
the infected host, which could explain the more frequent severe forms
in individuals with low production of this cytokine, such as the elderly
or those with co-morbidities.

Therefore, type-I IFN deficiency could be a signature of severe forms
of COVID- 19 and could identify a high-risk population.

These results further suggest that the administration of IFN-alpha/Beta combined with anti-inflammatory therapy targeting IL-6 or TNF-a, or corticosteroids such as dexamethasone, in the most severe patients could
be a therapeutic avenue to be evaluated for severe forms of COVID-19.


========================================================================== Story Source: Materials provided by INSERM_(Institut_national_de_la_sante'_et_de_la_recherche
me'dicale). Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Je'ro^me Hadjadj, Nader Yatim, Laura Barnabei, Aure'lien Corneau,
Jeremy
Boussier, Nikai"a Smith, He'le`ne Pe're', Bruno Charbit, Vincent
Bondet, Camille Chenevier-Gobeaux, Paul Breillat, Nicolas Carlier,
Re'my Gauzit, Caroline Morbieu, Fre'de'ric Pe`ne, Nathalie Marin,
Nicolas Roche, Tali- Anne Szwebel, Sarah H Merkling, Jean-Marc
Treluyer, David Veyer, Luc Mouthon, Catherine Blanc, Pierre-Louis
Tharaux, Flore Rozenberg, Alain Fischer, Darragh Duffy, Fre'de'ric
Rieux-Laucat, Solen Kerne'is, Benjamin Terrier. Impaired type I
interferon activity and inflammatory responses in severe COVID-19
patients. Science, 2020; eabc6027 DOI: 10.1126/ science.abc6027 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200717101015.htm

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