Table 3.

Cytokines and superantigens in COVID-19 and Kawasaki disease.

Cytokines/ Superantigens	COVID-19	Kawasaki disease
Proinflammatory ILs	● IL-1B, IL-RA, IL-7, IL-8, and IL-9 are increased in both ICU and non-ICU patients with COVID-1926 ● IL-6/ IFN-γ ratio is higher in patients with COVID-1931 ● IL-2R and IL-6 are significantly elevated in patients with COVID-19, and expression increases with disease severity 39 ● IL-6 is significantly increased in COVID-19 patients, and its levels in ICU patients are significantly higher than in non-ICU patients 24 ● 97% of patients with MIS-C who were tested had IL-6 ⩾ 5.0 pg/ml, with a median of 116.3 pg/ml overall 29	● IL-1, IL-2, IL-6, and IL-8 are upregulated in acute stage KD 40 ● IL-6 is significantly elevated in KD, and it decreases post-IVIG therapy 41 ● Patients with IL-6 >66.7 pg/ml are at higher risk for KD shock syndrome (KDSS) 42 ● IL-17, IL-6, and IL-23 (TH17 cytokines) are significantly upregulated 33 ● IL-1 has been found to facilitate antibody-mediated cytotoxicity in patients with KD 43
Proinflammatory Non-IL cytokines	● Basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1A, MIP-1B, PDGF, TNF-α, and VEGF are increased in both ICU and non-ICU patients with COVID-19, and ICU patients have higher concentrations of G-CSF, IP-10, MCP-1, MIP-1A, and TNF-α than non-ICU patients 26 ● TNF-α is significantly increased in COVID-19 patients, and its levels in ICU patients are significantly higher than in non-ICU patients 24	● TNF-α, IFN-γ, and MCP-1 are upregulated in acute stage KD 40 ● IFN-γ and TNF-α are significantly elevated in KD, and they decrease post-IVIG therapy. TNF-α is significantly decreased post-IVIG in patients without coronary artery lesions (CALs) and in IVIG responders, but is slightly increased in post-IVIG patients with CALs and in non-IVIG responders. 41 ● IFN- γ and TNF have been found to facilitate antibody-mediated cytotoxicity in patients with KD 44 ● Patients with IFN-γ >8.35 pg/ml are at higher risk for KD shock syndrome (KDSS) 42
Anti-inflammatory cytokines (IL and Non-IL)	IL-10 is increased in both ICU and non-ICU patients with COVID-19, and ICU patients have higher concentrations of IL-10 than non-ICU patients24,26	● IL-4, and IL-10 are upregulated in acute stage KD 40 ● IL-10 is significantly increased in KD, and it decreases post-IVIG 41 ● Patients with IL-10 >20.85 pg/ml are at a higher risk for KD shock syndrome (KDSS) 44 ● TGF-β (Treg cytokine) is low in patients with KD 33
Superantigens	The Spike (S) glycoprotein of SARS-CoV-2 has a high affinity TCR Vβ-binding epitope (P681RRA684) that is similar in sequence and structure to bacterial SAGs, such as Staphylococcal enterotoxin B (SEB), and there is greater stabilization and binding of S with TCR Vβ in a European strain (D839Y/N/E) 37	● KD-specific serum molecules are similar to molecule associated molecular patterns (MAMPs) from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis, and Staphylococcus aureus 45 ● TSST-1 producing strains of S. aureus have been isolated in patients with KD 45 ● Hemolytic Streptococci SAGs have been implicated in KD 46 ● Murine models of KD have demonstrated the induction of coronary arteritis using a SAG found within Lactobacillus cillus casei cell wall extract (LCWE) 47

Abbreviations: G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; ICU, intensive care unit; IFN, interferon; IP-10, interferon-γ-inducible protein 10; MCP-1, monocyte chemoattractant protein-1; MIP, macrophage inflammatory protein; PDGF, platelet derived growth factor; TGF, transforming growth factor; TNF, tumor necrosis factor; TSST-1, toxic shock syndrome toxin 1.