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Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage
  • Sandra Amor,
  • Laura Fernandez Blanco,
  • David Baker
Sandra Amor
Amsterdam UMC , VU medisch centrum School of Medical Sciences

Corresponding Author:[email protected]

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Laura Fernandez Blanco
VU medisch centrum School of Medical Sciences
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David Baker
Queen Mary University of London
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Abstract

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses SARS CoV-2 has evolved strategies to circumvent innate immune detection including low CpG levels in the genome, glycosylation to shield essential elements including the receptor binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion SARS-CoV-2 infection does activate innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines, and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin-angiotensin system due to downregulation of angiotensin converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.
03 Aug 2020Submitted to Clinical & Experimental Immunology
04 Aug 2020Submission Checks Completed
04 Aug 2020Assigned to Editor
12 Aug 2020Reviewer(s) Assigned
07 Sep 2020Review(s) Completed, Editorial Evaluation Pending
08 Sep 2020Editorial Decision: Revise Minor
11 Sep 20201st Revision Received
11 Sep 2020Review(s) Completed, Editorial Evaluation Pending
11 Sep 2020Editorial Decision: Accept
30 Oct 2020Published in Clinical and Experimental Immunology volume 202 issue 2 on pages 193-209. 10.1111/cei.13523