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. 2020 Jun;8(6):544-546.
doi: 10.1016/S2213-2600(20)30226-5. Epub 2020 May 4.

Immunomodulation in COVID-19

Nicholas E Ingraham  1 , Sahar Lotfi-Emran  2 , Beth K Thielen  3 , Kristina Techar  4 , Rachel S Morris  5 , Shernan G Holtan  6 , R Adams Dudley  7 , Christopher J Tignanelli  8
Affiliations

Immunomodulation in COVID-19

Nicholas E Ingraham et al. Lancet Respir Med. 2020 Jun.
No abstract available

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Figures

Figure
Figure
SARS-CoV-2 interaction with the inflammatory system and therapy targets within the system TLR4, AT1R, IL-6, IL-1, IL-18, type 1 IFNs, and IFN-γ receptor binding activates specific signalling cascades and translocation of nuclear transcription factors into the nucleus (blue ellipse), where they interact with their respective chaperones (NF-KB) or their targeting sequences on DNA (ISRE, GAS) to activate the production of multiple proteins including additional cytokines, chemokines, cell surface molecules, and more. SARS-CoV-2 also directly interacts with ACE2 (via S protein) causing uninhibited Ang II activation of AT1R while also decreasing TLR4 inhibition; in addition, SARS-CoV-2 inhibits TYK 2 (vis NSP1), further driving inflammation by causing downstream effects that overlap with the immunomodulatory pathway. Anticytokine, JAK inhibitors, and antihypertensives can limit hyperinflammation by interacting and inhibiting these signalling cascades. ACE=angiotensin converting enzyme. Ang=angiotensin. ATR1=type 1 angiotensin II receptor. AT2R=type 2 angiotensin II receptor. COX=cyclooxygenase. GAS=IFN-γ activation site. ICAM=intercellular adhesion molecule. IL=interleukin. IFN=interferon. IRF=IFN regulatory factor. ISG=IFN-stimulated gene. ISRE=IFN-stimulated response element. JAK=Janus kinase. MCP=monocyte chemoattractant protein. NSP=non-structural protein. PD-1=programmed cell death 1. R=receptor. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. TGF=transforming growth factor. TLR=toll-like receptor. TNF=tumour necrosis factor. TRIF=TIR-domain-containing adapter-inducing interferon-β. TXA=thromboxane. TYK=tyrosine kinase. VEGF=vascular endothelial growth factor. *JAK inhibitors: ruxolitinib, tofacitinib, baricitinib, peficitinib, fedratinib, and upadacitinib.
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References

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