To better understand the “cytokine storm” sometimes seen in extreme cases of COVID-19, researchers compared research papers related to the immune system responses from the SARS-CoV-2 virus and other common respiratory viruses. They were looking for identifying features that trigger the body to have an over-exuberant cytokine response to infection, such as in those individuals who experience severe COVID-19 illness.
The cytokine storm occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with COVID-19 for a subgroup of patients.
The team from the Earlham Institute (EI), the Quadram Institute, and the University of Birmingham in the U.K. analyzed 5,000 scientific studies, ultimately focusing on 38 cytokines, to find those containing immune response data from patients with COVID-19 and other viruses response for outbreaks in the past 20 years — SARS-CoV, MERS-CoV, H5N1, H7N9. In particular, they focused on studying changing cytokine levels. Their findings are published in a paper in Frontiers in Immunology.
While SARS-CoV-2 cases have distinct similarities to both influenza patients and those who were infected in previous coronavirus outbreaks (SARS-CoV, MERS-CoV), they appear to have different immune mechanisms that make SARS-CoV-2 uniquely dangerous.
The cytokine response during viral infection is a dynamic process, with multiple changes in the cytokine levels during the course of the infection. In their analysis, the team discovered that after infection from SARS-CoV-2, the cytokine response differs for a few important cytokines from these other viruses which can also trigger an over-exuberant cytokine reaction. For example, SARS-CoV-2 does not elevate all of the expected cytokines, such as IL-2, IL-10, IL-4 and IL-5, compared to similar viruses.
“We showed that SARS-CoV-2-mediated infections are characterized by a clear dysregulation of type-I IFN response and, consequently, the downstream cytokine signatures, such as IL-4, IL-12, IL-2, and IL-10s, and the downstream type-II IFN response,” the authors write.
Type-I IFN signaling cascades attenuate inflammation to avoid tissue damage during viral infection. Influenza A and coronavirus infections can trigger increased levels of type-I IFN-α and IFN-β, reflecting the normal initiation of this signaling pathway in response to viral infections. However, in severe infections with SARS-CoV-2, the type-I IFN signaling is impaired, culminating in a weak response, if any.
The team’s goal is to provide a map of unique and common cytokine immune responses from SARS-CoV-2 and other respiratory viruses as an aid in finding new ways to ward off or alleviate the cytokine storm in COVID-19 and other viruses.