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Review
. 2021 Jun 4;9(6):596.
doi: 10.3390/vaccines9060596.

The Many Faces of Innate Immunity in SARS-CoV-2 Infection

Nicholas Hanan  1 , Ronnie L Doud Jr  1 , In-Woo Park  1   2 , Harlan P Jones  1   2 , Stephen O Mathew  1   2
Affiliations
Review

The Many Faces of Innate Immunity in SARS-CoV-2 Infection

Nicholas Hanan et al. Vaccines (Basel). .

Abstract

The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia. Elevated interleukin (IL)-6 and IL-8 leads to overactivity and is a prominent feature of severe COVID-19 patients. IL-6 can result in lymphopenia; where COVID-19 patients typically have significantly altered lymphocyte subsets. IL-8 attracts neutrophils; which may play a significant role in lung tissue damage with the formation of neutrophil extracellular traps leading to cytokine storm or acute respiratory distress syndrome. Several factors like pre-existing co-morbidities, genetic risks, viral pathogenicity, and therapeutic efficacy act as important modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses. In this review, we discuss the role of the innate immune system at play with other important modifiers in SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; cytokines; innate immunity.

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Conflict of interest statement

The authors declare that the review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Integrated framework of important modifiers of SARS-CoV-2 risks for disease intersecting with innate immunity. Genetic risks, pre-existing co-morbidities, viral pathogenicity, and therapeutic efficacy are vital modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses.
Figure 2
Figure 2
Potential severe patient hyperinflammation progression in COVID-19. Spike protein (A) activates macrophages (B) that release various proinflammatory cytokines; (C) IL-8 attracts neutrophils (D), which have the potential to degranulate (E) and form NETs (F). NETs can potentially form a positive feedback loop with macrophages and IL-1β release. Macrophages release IL-6 and TNF that inhibits and causes apoptosis in T cells and NK cells (G), causing or exacerbating lymphopenia.
See this image and copyright information in PMC

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