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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus causing coronavirus disease 2019 (COVID-19)
In Part 1 of this review, we concluded that SARS-CoV-2 deliberately sabotages early innate immunity, which along with inborn errors of innate sensing and IFN signalling results in increased viral load in severe COVID-19
We focus on innate immunity because there is a bias towards these cells in COVID-19, these findings should be taken in context with the entire immune response, as adaptive systems likely activate innate cells through antibodies and cytokines
Summary
The first responders to viral infection in coronavirus disease 2019 (COVID-19) are the cells of the innate immune system, including natural killer (NK) cells, monocytes, macrophages and neutrophils. After migrating to the site of infection and recognizing the virus from conserved features, innate cells initiate responses to eliminate the virus and coordinate the adaptive immune system. In some cases, innate cells have been shown to contribute to viral dissemination and tissue damage which is associated with severe COVID-19 disease and fatal outcomes. It is critical to evaluate innate immunity in the context of COVID-19 to predict outcome and facilitate development of therapeutic interventions
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