A new study published in J Exp Med shows that innate immune dynamics in early COVID19 - host response can slow viral replication from low infectious dose and block replication if defenses are boosted by recent common cold infection.[1]
There is strong evidence that the IFN response protects against severe COVID-19. Most respiratory viruses induce an IFN response in the airway, although the kinetics and magnitude vary, and most are also highly susceptible to this host defense mechanism if it is sufficiently activated during active viral replication.
SARS-CoV-2—Doubling Time of ~ 6 Hours
SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline.
Early IFN Response Protects against Severe COVID-19
There is strong evidence that the IFN response protects against severe COVID-19. Most respiratory viruses induce an IFN response in the airway, although the kinetics and magnitude vary, and most are also highly susceptible to this host defense mechanism if it is sufficiently activated during active viral replication.
The mucosal IFN response is initiated when pattern recognition receptors within epithelial cells and immune cells sense general features shared by many viruses, such as common structural features of viral RNA. This recognition event triggers expression of type I and type III IFNs and IFN-stimulated genes (ISGs). Secreted IFNs, in turn, bind to cell surface receptors on nearby cells, amplifying ISG expression and creating an antiviral state in the mucosal barrier.[2-4]
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| Figure 1. (a) Kinetics of SARS-CoV-2 replication and interferon response in patients (b) Rhinovirus infection blocks SARS-CoV-2 (c) Inhibiting ISGs accelerates SARS-CoV-2 (source: [1]) |
Recent Common Cold Infection Can Protect
Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication (Figure 1b). Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose (Figure 1c).
The rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures of 33–35 °C (91–95 °F), the temperatures found in the nose.
To recap: new results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.
References
- Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics
- Schneider, W.M., M.D. Chevillotte, and C.M. Rice. 2014. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32:513–545.
- Odendall, C., and J.C. Kagan. 2015. The unique regulation and functions of type III interferons in antiviral immunity. Curr. Opin. Virol. 12:47–52.
- Iwasaki, A. 2012. A virological view of innate immune recognition. Annu. Rev. Microbiol. 66:177–196.
- Interferon-Stimulated Genes: A Complex Web of Host Defenses (good)
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