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July 20, 2020 Monday 08:39:36 PM IST

Why Some Patients are More Prone to Covid? A French Research Team Has The Answer

photo by Gerd Altman for Pixabay.com

The deficiency of type I interferons (IFN) or its impaired response that causes persistent viral load and excessive inflammatory response may be the reasons why some patients develop severe forms of Covid-19, according to a research team of AP-HP, Inserm, University of Paris and others.

Approximately 5% of people with Covid-19 develop a severe or critical form, including severe pneumonia that develops into acute respiratory distress syndrome. While these forms sometimes occur at the onset of the disease, clinical observations generally describe a two-step progression of the disease, beginning with a mild to moderate form, followed by respiratory worsening 9 to 12 days after the onset of the first symptoms. This sudden development suggests a deregulation of the host's inflammatory response. A growing number of indications suggest that this aggravation is caused by a sharp increase in cytokines. This runaway inflammatory response is correlated with massive infiltration into the lungs of innate immune cells, namely neutrophils and monocytes, creating lung damage and acute respiratory distress syndrome.

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 reveals that low levels of type 1 IFN in plasma precede the clinical worsening of patients and their transfer to intensive care. Circulating levels of IFN 1 would even characterize each stage of disease, with the lowest rates observed in the most severe patients. These results suggest that in SARS-CoV-2 infection, production of type IN IFN is inhibited in the infected host, which may explain the more common severe forms in individuals with low cytokine production, such as the elderly or those with comorbidities.

Therefore, type IN deficiency could be a signature of the severe forms of COVID-19 and could identify a high-risk population.These results further suggest that the administration of IFN-alpha combined with an anti-inflammatory therapy targeting IL-6 or TNF-, or corticosteroids such as dexamethasone, in the most severe patients could be a therapeutic avenue to evaluate to curb severe forms of COVID-19.


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