Interferon Role In Severe COVID-19 Patients
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Interferon’s Role In Severe COVID-19 Patients

The broad spectrum of disease severity is one of the hallmarks of SARS-CoV-2 infection. COVID-19 virus is seen to cause a mild disease course that resolves on its own in some people and severe symptoms needing intensive care with mechanical ventilation are developed in some people. The focus of many COVID-19 researchers has been uncovering the cause of the difference between mild disease versus severe, and understanding this distinction. The main focus of some of the leading hypotheses is the role of the immune modular interferon (IFN).

Now, a team from the Republic of Korea performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with severe influenza, and patients with mild or severe COVID-19, to unravel patients’ immune responses. According to their findings, in exacerbating inflammation in severe COVID-19, the type I IFN response is seen to play a pivotal role.

A detailed look at patients’ immune responses to severe cases of COVID-19 is provided by the single-cell RNA sequencing analysis of more than 59,000 cells (PBMCs) from three different patient cohorts.

The RNA from a total of 59,572 blood cells obtained from four healthy donors, five patients with

severe influenza, and eight patients with mild or severe COVID-19, were sequenced by the research team at Korea Advanced Institute of Science and Technology (KAIST) led by Seong Seok Lee at the Graduate School of Medical Science and Engineering. Increased regulation of the TNF/IL-1ß-driven inflammatory response was seen in patients in both the mild and severe COVID-19 cohorts, while an increased IFN-I response was exhibited by patients with severe COVID-19. By comparison, increased expression of various IFN-stimulated genes was seen in patients with severe flu but they did not experience TNF/IL-1ß responses as seen in patients with COVID-19.  Unlike the flu cohort, a combination that was also not seen in patients with milder cases of COVID-19 was seen in patients in the severe COVID-19 cohort, as they exhibited the IFN-I signature concurrently with TNF/IL-1ß-driven inflammation.

The authors observed that, across all types of cells among PBMCs, COVID-19 patients showed hyper-inflammatory signatures, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to patients with severe influenza. Additionally, type I IFN response co-existed with the TNF/IL-1β-driven inflammation in classical monocytes from patients with severe COVID-19, and this was not observed in patients with milder COVID-19 infection.

According to the results, it suggests that increased regulation of the type I interferon (IFN-I) inflammation-triggering pathway—a sign that the researchers also observed in patients hospitalized with severe cases of influenza is experienced in patients with severe COVID-19.

The team that they could observe by comparing COVID-19 and severe influenza that the up-regulation of various interferon-stimulated genes (ISGs) was prominent in severe influenza, whereas the TNF/IL-1β-driven inflammatory response was dominant in COVID-19 across all types of cells among PBMCs.

The scientists, based on their results propose that in patients with severe COVID-19, the IFN-I response aggravates inflammation. In determining the outcome of SARS-CoV-2 infection, support targeting IFN-I as a potential treatment strategy for severe COVID-19, their results, along with past mouse studies that highlight how the timing of IFN-I expression is critical.

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Interferon’s Role In Severe COVID-19 Patients