Infection with SARS-CoV-2 causes the respiratory disease COVID-19 which, for the majority of individuals, is a relatively mild disease that will resolve on its own without intervention over the course of a couple of weeks. However, some patients develop severe symptoms that require oxygen or mechanical ventilation. The disease has a high mortality rate in patients requiring mechanical ventilation or oxygen.
Relatively little is known about the reasons why some patients develop severe symptoms and others have mild symptoms or none at all. Determining why there is such variation has been the subject of considerable research over the past few months. There have been several hypotheses proposed, but multiple research teams have suggested the immune response plays a key role in the severity of the symptoms and, specifically, immune modular interferon (IFN).
Inteferons are signaling proteins that are made and released by the body in response to the presence of certain viruses. When a virus invades a cell, inteferons are released which signal to other cells that a virus has invaded, triggering killer immune cells to attack the viruses and prevent them from multiplying. Two types of interferons are release in response to viruses, interferon-alpha and interferon-beta. These trigger white blood cells to release interferon-gamma. Interferons place the immune system on alert, help to identify the viruses to be attacked, and instruct the immune system to attack the viruses.
Researchers in the Republic of Korea have been investigating the role of interferons in the response to infection with SARS-CoV-2. The researchers 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. The research suggests the type I IFN response plays a key role in driving inflammation in severe cases of COVID-19.
Patients with mild or severe COVID-19 showed increased regulation of the TNF/IL-1ß-driven inflammatory response and patients with severe COVID-19 also had an increased IFN-I response. The increased IFN-I response was not evident in patients with mild COVID-19 symptoms but was also observed in hospitalized patients with severe influenza. Unlike influenza, patients with severe COVID-19 exhibited the IFN-I signature concurrently with TNF/IL-1ß-driven inflammation.
“In the current study, we confirmed the results from previous studies by showing that the TNF/IL-1β inflammatory response is dominant in COVID-19 although a small number of patients were enrolled,” explained the researchers. “However, we also found that severe COVID-19 is accompanied by the IFN-I response in addition to the TNF/IL-1β response. These results indicate that the IFN-I response might contribute to the hyper-inflammatory response by potentiating TNF/IL-1β-driven inflammation in severe progression of COVID-19.”
You can read more about the study in the paper – Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 – which was recently published in the journal Science Immunology. DOI: 10.1126/sciimmunol.abd1554