Researchers discover a key factor that predicts COVID-19 disease severity

A study led by Drs. Laia Alsina and Iolanda Jordan from the IRSJD evidences a key factor that predicts the severity of COVID-19: an alteration of the first immune response to SARS-CoV-2 infection, in key molecules in the anti-infective response. The study has been published in open access in the journal iScience.

Since 2020, the scientific community has been striving to find out why the clinical manifestations of COVID-19 ranges from asymptomatic to severe. In addition, while the symptoms in adults can be very varied, in children the disease seems to be milder, due to certain immune properties of these.

Various studies suggest that one of the reasons why there are such different clinical manifestations in COVID-19 and one of the factors involved in the critical course of the disease is related to the interferon. An essential signaling protein in defense against viral infections. This protein is produced by cells of the immune system and is considered one of the most effective first elements of antiviral response.

The relationship between interferon and cytokine overproduction

When the cell is infected by a virus, it secretes interferons, generating an activation of antiviral defenses in nearby cells: they limit the spread of the virus, modulate the innate immune response, and activate the adaptive immune system. In fact, interferon is a type of cytokine, which are small proteins crucial for controlling the growth and activity of other cells in the immune system. This type of immune response is even more important in controlling the SARS-CoV-2 virus since the infection has been shown to cause a dysregulation of the interferon response.

It seems that one of the factors that causes the severe clinical course of COVID-19 is a minimal or delayed interferon response, which leads to an inefficient antiviral response in the initial phases of the infection and to an overproduction of cytokines and a hyperinflammatory state. For this reason, in this study, they have compared the response of interferon and other cytokines in more than 80 patients, both adults and children, with different degrees of severity of COVID-19. The aim: determining patterns of cytokines that help screen patients and be able to personalize treatments in the future.

The interferon response, essential to determine the severity of COVID-19

The study results confirm that patients with severe COVID-19 have high levels of cytokines due to this dysregulated interferon antiviral response. In addition, researchers selected two genes, one of them associated with interferon expression, and found that low levels of the CIITA gene and high levels of the SOCS1 gene were indicative of the most severe cases of COVID-19, both in children and adults.

"The main finding of this study is that the interferon response is different depending on the severity of the disease. Therefore, the analysis of some cytokines derived from the expression pattern of the selected genes could be useful as a future biomarker when screening the population most at risk of severe COVID-19", comments Dr. Laia Alsina, group leader in the Study of Immune Deficiency Diseases in Pediatrics (GEMDIP).

"Moreover, it shows that some circulating cytokine levels are tightly correlated with the expression of the genes that produce interferon, which could be very useful as per future biomarkers and therapeutics targets of the disease" adds Dr. Iolanda Jordan, a researcher in the group Immune and Respiratory Dysfunction in Critically Ill Children.

It must be said that these results are preliminary and must be confirmed in additional studies with larger patient samples, but in the meantime the interferon genes could be considered when looking for therapeutic targets against COVID-19.

This study is framed within the Kids Corona platform, leaded by the SJD Barcelona Children’s Hospital initiated in 2020.

Reference paper

M.Girona-Alarcon, G.Argüello, A.Esteve-Sole et al, Low levels of CIITA and high levels of SOCS1 predict COVID-19 disease severity in children and adultsiScience, 2022, Jan;25(1), DOI:

"The main finding of this study is that the interferon response is different depending on the severity of the disease"