The evolution of patients infected with the new coronavirus has frequently been described as unpredictable by clinicians, although in most cases, mild to moderate form generally succeed complications, respiratory 9 to 12 days after onset early symptoms. However, being able to detect patients at high risk for severe complications is essential to improve their management and prognosis. Whereas in these patients, this sudden deterioration in the state of health has been explained over the studies by a kind of cytokine storm, the French team here identifies a unique and unexpected immunological phenotype in severe and critical patients: a severely impaired response of interferons (IFN) type I, associated with a persistent viral load in the blood and an excessive inflammatory response.
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Discovery of an immunological signature characteristic of patients at risk of complications
- By analogy with a genetic disease leading to a nearby pulmonary pathology, the researchers had first hypothesized an excessive production of type 1 interferons (IFN), a marker of the response to infections in the most severely affected. However, the observation in these patients is, on the contrary, a production and an activity of type I IFN greatly reduced;
- second characteristic, a persistent viral load in the blood, which reveals the poor control of viral replication by the immune system which participates in the excessive inflammatory response;
- this inflammation leads to an increase in the production and signaling of tumor necrosis factor (TNF) -alpha and interleukin IL-6, a pro-inflammatory cytokine.
The level of type 1 interferons seems to be characteristic of each stage of the disease
- low levels of IFN type 1 in plasma precede the clinical worsening of patients and their transfer to intensive care;
- the lowest rates are then observed in the most seriously ill patients;
- “The deficiency in type I IFN could be a signature of the serious forms and make it possible to identify the patients most at risk of these complications”.
New therapeutic avenues? The authors suggest that compensating for these low levels of type 1 IFN, by administering IFN-alpha, combined with anti-inflammatory therapy targeting IL-6 or TNF-α, or corticosteroids such as dexamethasone , in the most severe patients may be a possible option to stop severe forms of COVID-19.
In conclusion, the deficiency of type I IFN in the blood could be a predictor of severe forms of COVID-19 and make it possible to detect patients who are going to need special care and monitoring.
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