Table 4.
Cytokine and chemokine profiles associated with COVID-19 severity
| Author | Technique | Patients N | Control N | Cytokines | RoB | |
| COVID-19 (mild, moderate and/or severe) vs control | Chi et al42 | Multiplex (48 cytokines) | 70 (22 mild 36 moderate, 8 severe, 4 convalescent) |
4 HC | ↑ IL-1β, IL-1Ra, IL-2, IL-2Ra, IL-6, IL-7, IL-8, IL-9, IL-10, IL-1, IL-15, IL-17, IL-18 ↑ TNF-α, IFN-α2, IFN-γ, G-CSF, M-CSF, TRAIL, FGF, PGDF, Eotaxin, CXCL1/GRO-α ↑ MCP3, MIP-1α, MIG, MCP-1 |
High |
| Xu et al43 | Multiplex (48 cytokines) | (7 mild, 6 severe, 10 fatal) | 4 HD | ↑ 20 cytokines, chemokines and growth factors, including IL-1α, IL-1β, IL-4, IL-5, IL-7, IL-12 p40, IL-13, IL-16, TNF-α, TRAIL, IFN-α2, CXCL1/GRO-α, CXCL12/SDF-1α, CCL11/Eotaxin, CCL27/CTACK, G-CSF, LIF, MIF, SCGF and VEGF | High | |
| Fraser et al41 | Multiplex (57 cytokines) | 10 severe | 10 HD | ↑ elastase 2, HSP-70, IL-1RA, IL-6, IL-8, ↑ MCP-1 monokine induced by γ-IFN, MMP8. ↑ resistin, TNF, IL-10, IL-18, M-CSF, granzyme B, thrombospondin-1, MIP-1β, MMP-2 ↑ neutrophil gelatinase-associated lipocaline, IL-15, IFN-γ |
Low | |
| Arunalacham et al27 | Multiplex (17 cytokines) | 36 (HK, 27 mild, 5 moderate, 4 severe) 40 (ATL) 24 influenza (ATL) |
45 HD (HK) 24 HD (ATL) |
↑ IL-6, MCP-3, TNFα, EN-RAGE, TNFSF14 and Oncostatin M | High | |
| Lucas et al26 | Multiparametric flow cytometry | 113 (moderate 80, severe 33) | 108 HD | ↑ IL-1α, IL-1β, IL-17A, IL-12 p70 and IFN-α | Low | |
| COVID-19 vs other diseases | Wilson et al45 | Luminex (76 cytokines) |
15 (9 critical) vs 16 critical sepsis and 12 critical ARDS | None | ↑ thymic stromal lymphopoietin lower in moderate and severe COVID-19 compared with ARDS and sepsis IL-16 lower in moderate COVID-19 compared with ARDS and sepsis |
High |
| Arunalacham et al27 | Multiplex (17 cytokines) | 36 (HK, 27 mild, 5 moderate, 4 severe) 40 (ATL) 24 influenza (ATL) |
45 HD (HK) 24 HD (ATL) |
↑ TNFSF14 in COVID-19 patients vs other pulmonary diseases | High | |
| Severe COVID-19 vs control | Sims et al44 | Multiplex (184 cytokines)+ IL-19 assay | 25 (6 mild, 4 moderate,8 severe, 7 critical) | 20 HD | ↑ 21-fold IFN-γ, 18-fold IL-6, IL-10, MCP-1, MCP-2, 12-fold MCP-3, 10-fold CXCL10, 2-fold MCP-3 IL-19 (p<0.001) | High |
| Lucas et al26 | Multiparametric flow cytometry | 113 (moderate 80, severe 33) | 108 HD | IL-1α, IL-1β, IL-6, IL-10, IL-18 and TNF-α are correlated with severity | Low | |
| Del Vallee et al47 | ELISA | 1484 | HD CAR T-cell treated patients with or without cytokine release syndrome |
↑ IL-6 (mean 332 pg/mL) (p < 0.0001), IL-8 ((mean 110 pg/mL) (p<0.0001) and TNF-α (mean 28 pg/mL) (p<0.0001) Strong predictors of disease severity |
High | |
| Mild COVID-19 vs severe | Chi et al42 | Multiplex (48 cytokines) | 70 (22 mild, 36 moderate 8 severe, 4 convalescent) |
4 HD | ↑ IL-6, IL-7, IL-10, G-CSF, M-CSF IP-10, MCP-3, MIP-1α, MIG, MCP-1 |
High |
| Sims et al44 | Multiplex (184 cytokines)+ IL-19 assay | 25 (6 mild, 4 moderate,8 severe, 7 critical) | 20 HD | ↑ IFN-γ, IL-1RA, IL-6, IL-10, IL-19, MC-1, MCP-2, MCP-3, CXCL9, CXCL10, CXCL5, EN-RAGE, and poly(ADP-ribose) polymerase 1 (p<0.001) | High | |
| Xu et al43 | Multiplex (48 cytokines) | (7 mild, 6 severe, 10 fatal) | 4 HD | ↑ 16 cytokines, chemokines and growth factors, including HGF, CXCL8/IL-8, CCL7/MCP-3, CCL2/MCP-1, CXCL9/MIG, CXCL10/IP-10, IL-6, IL-18, IL-2, MCSF, IL-1Rα, IL-2Rα/CD25, IFN-γ, CCL3/MIP-1α, basic FGF and SCF were significantly higher in fatal than severe and/or mild COVID-19 patients | High | |
| Arunalacham et al27 | Multiplex (17 cytokines) | 36 (HK, 27 mild, 5 moderate, 4 severe) 40 (ATL) 24 Influenza (ATL) |
45 HD (HK) 24 HD (ATL) |
↑ IL-6, MCP-3, EN-RAGE, TNFSF-14, and oncostatin M | High | |
| Lucas et al26 | Multiparametric flow cytometry | 113 (moderate 80, severe 33) | 108 HD | ↑ thrombopoietin, IL-33, IL-16, IL-21, IL-23, IFN-λ, Eotaxin and Eotaxin 3 | Low | |
| Mild COVID-19 vs moderate | Chi et al42 | Multiplex (48 cytokines) | 70 (22 mild, 36 moderate, eight severe, 4 convalescent) |
4 HD | ↑ IL-18, M-CSF, IP-10 | High |
| Arunalacham et al27 | Multiplex (17 cytokines) | 36 (HK, 27 mild, 5 moderate, 4 severe) 40 (ATL) 24 influenza (ATL) |
45 HD (HK) 24 HD (ATL) |
↑ EN-RAGE, TNFSF14 and Oncostatin M | High | |
| Moderate COVID-19 vs severe | Chi et al42 | Luminex | 70 (22 mild, 36 moderate eight severe, 4 convalescent) |
4 HD | ↑ MCP-3, MIG and MIP-1α | High |
| Wilson et al45 | Luminex (76 cytokines) |
15 (9 critical) vs 16 critical sepsis and 12 critical ARDS | None | ↑ PDGF-BB | High | |
| Wilson et al45 | Luminex (76 cytokines) |
15 (9 critical) vs 16 critical SEPSIS and 12 critical ARDS | None | No difference between four groups in IL-1β, IL-1RA, IL-6, IL-8, IL-18 and TNF-α and another 64 cytokines | High | |
| Arunalacham et al27 | Multiplex (17 cytokines) | 36 (HK, 27 mild, 5 moderate, 4 severe) 40 (ATL) 24 influenza (ATL) |
45 HD (HK) 24 HD (ATL) |
↑ IL-6, oncostatin M | High | |
| Lucas et al26 | Multiparametric flow cytometry | 113 (moderate 80, severe 33) | 108 HD | After day 10, the following markers declined: IL-1α, IL-1β, IL-17A, IL-12 p70 and IFN-α in patients with moderate disease, while patients with severe COVID-19 maintained elevated levels Following day 10, IFNα, IFNλ, IL-1β, IL-1Ra, IL-18, IL-33, Eotaxin-2 remained high in severe while decreased in moderate |
Low | |
| Mild/severe vs critical | Xu et al43 | Multiplex (48 cytokines) | (7 mild, 6 severe, 10 fatal) | 4 HD | ↑ 16 cytokines, chemokines and growth factors, including HGF, CXCL8/IL-8, CCL7/MCP-3, CCL2/MCP-1, CXCL9/MIG, CXCL10/IP-10, IL-6, IL-18, IL-2, MCSF, IL-1Rα, IL-2Rα/CD25, IFN-γ, CCL3/MIP-1α, basic FGF and SCF Among these IFN-γ, IL-1Rα, IL-2, IL-2Rα, IL-6, CXCL8, IL18, CCL2, CCL3, SCF, HGF and basic FGF were upregulated to similar levels at the early stages and then upregulated significantly in fatal patients at day 14 |
High |
ARDS, acute respiratory distress syndrome; CCL, C-C motif chemokine ligand; CEACAM-8, CEA cell adhesion molecule; CXCL, chemokine (C-X-C motif) ligand; FGF, fibroblast growth factor; G-CSF, granulocyte colony-stimulating factor; HGF, Hepatocyte Growth Factor; HSP, heat shock protein; IFN, interferon; IL, interleukine; IP-10, interferon gamma-induced protein 10; LIF, leukaemia inhibitory factor; MCP, monocyte chemotactic protein; M-CSF, macrophage colony stimulating factor; MIF, macrophage migration inhibitory factor; MIG, monokine induced by gamma-interferon; MIP, monocyte chemotactic protein; MMP-2, matrix metalloproteinase; PDGF-BB, platelet-derived growth factor; SCF, stem cell factor; SCGFB, stem cell growth factor beta; SDF-1α, stromal cell-derived factor 1; CAR T-cell, chimeric antigen receptor T cells; TNF, tumour necrosis factor; TNFSF14, tumour necrosis factor ligand superfamily member 14; TRAIL, tumour necrosis factor–related apoptosis–inducing ligand; VEGF, vascular endothelial growth factor.