Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology

Rodrigues, Patrícia R. S. ORCID: https://orcid.org/0000-0003-0768-0013, Alrubayyi, Aljawharah, Pring, Ellie, Bart, Valentina M. T., Jones, Ruth, Coveney, Clarissa, Lu, Fangfang, Tellier, Michael, Maleki Toyserkani, Shayda ORCID: https://orcid.org/0000-0002-9829-2851, Richter, Felix C., Scourfield, D. Oliver, Gea-Mallorquí, Ester and Davies, Luke C. 2020. Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology. Oxford Open Immunology 1 (1) , iqaa005. 10.1093/oxfimm/iqaa005

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Abstract

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)
ISSN:	2633-6960
Date of First Compliant Deposit:	28 April 2021
Date of Acceptance:	13 November 2020
Last Modified:	05 Jan 2024 06:20
URI:	https://orca.cardiff.ac.uk/id/eprint/140827

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