This is a summary, written by members of the CITF Secretariat, of:

Banerjee A, El-Sayes N, Budylowski P, Jacob RA, Richard D, Maan H, Aguiar JA, Demian WL, Baid K, D’Agostino MR, Ang JC, Murdza T, Tremblay B.J.-M, Afkhami S, Karimzadeh M, Irving AT, Yip L, Ostrowski M, Hirota JA, Kozak R, Capellini TD, Miller MS, Wang B, Mubareka S, McGeer AJ, McArthur AG, Doxey AC, Mossman K, Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. ISCIENCE. 2021 Apr 23. doi: 10.1016/j.isci.2021.102477.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

CITF Leadership Group member Dr. Allison McGeer and CITF-funded researcher Dr. Mario Ostrowski collaborated on a recent publication in iScience where they attempted to examine the early immune responses to SARS-CoV-2 infection. In an in vitro model, they found that infected cells secreted particular inflammatory proteins, and this was consistent with observations in patients suffering from COVID-19. They inferred that these proteins contribute to disease severity.

Main conclusions:

  • An early and robust type I IFN response may protect humans from COVID-19 disease progression.
  • Authors indicate this might be a potential mechanism to explain the large number of asymptomatic infections and suggest that these observations should be leveraged to develop drug candidates.

Prior to the production of antibodies or activation of T cells against the SARS-CoV-2 virus, a more primordial and evolutionary older alarm system is triggered by innate immune cells. This innate immune system is guided by soluble molecules known as type I interferons (IFNs), and is the foundation of our defensive response against viral infections. When cells are stimulated by IFN they produce a series of other antiviral proteins to protect themselves and neighboring cells from infection. This is known as an IFN response. The authors of this study demonstrated that SARS-CoV-2 infection of human lung cells in vitro induces the production of type I IFN and the subsequent cascade of events typical of the antiviral IFN response.

The authors also evaluated the presence of several other proteins involved in the anti-inflammatory or antiviral immune response, collectively known as cytokines, in the sera of 20 patients that recovered from COVID-19, half had moderate and half had severe COVID-19. They reported characteristic and distinct cytokine profiles differentiating healthy individuals, and patients with moderate or severe COVID-19. Samples from patients with severe COVID-19 had significantly higher Interleukin-6 (IL-6), IL-5, macrophage colony-stimulating factor 1 (M-CSF), IL-8, tumor necrosis factor a (TNFa), TNFb and granulocyte colony-stimulating factor 1 (G-CSF) relative to those suffering from moderate infection or healthy individuals. Moreover, samples from patients with moderate COVID-19 had higher type I IFN and IL-10, compared to healthy individuals and severe cases of COVID-19.

Finally, they showed that the level of IFN detected in patients with moderate COVID-19 was sufficient to prevent SARS-CoV-2 replication in human lung cells in vitro. Altogether, this work suggests that an early and robust type I IFN response may protect humans from COVID-19 disease progression. The authors indicate that this might be a potential mechanism to explain the large number of asymptomatic infections, and also suggest that these observations should be leveraged to develop drug candidates.