Table 2.
Therapeutic immune biomarkers in COVID-19.
| Biomarkers | Intervention | Mechanistic pathway |
|---|---|---|
| ACE2 | Anti-ACE2 Abs, rhACE2-Fc fusion, srhACE2, and ACE2 inhibitors [14,15] | Blocking virus entry |
| ACE/Ang II | ACE inhibitors and srACE2 [13,14,15] | Decreasing Ang II synthesis, and increasing Ang 1−7 and Ang 1−9 synthesis |
| Ang 1−7/1−9 | srAng 1−7 and srAng 1−9 [14,15] | Increasing Ang 1−7 and Ang 1−9 synthesis |
| AT1R | Ang II receptor blockers [13] | blocking AT1R signaling |
| MUC | SYK inhibitor (Fostamatinib) [23] MUC-4 [24] |
Reducing MUC-1 synthesis Anti-apoptotic and anti-inflammatory properties |
| Surfactants | SP-A and SP-D [26] | Preventing viral attachment to the host cells |
| Type I IFNs | In early phase: IFN-α2 [56], IFN-β [57] and IFN-α2b [58] | Increasing NK cell cytotoxicity, increasing proliferation of macrophages and NK cells, and enhancing the expression of HLA-I and IFN-I |
| In late phase: IFN-α/β receptor blockers and antagonists [61] | Preventing excessive inflammatory responses | |
| C3a/C5a | C3 inhibitors (AMY-101), anti-C5 mAb (eculizumab and ravulizumab), and anti-C5a mAb (IFX-1) [89,90] | Inhibiting complement activation and monocyte/neutrophil migration to the sites of inflammation |
| IL-6 | Tocilizumab (anti-IL-6R mAb), sarilumab (anti-IL-6R mAb) and siltuximab (anti-IL-6 mAb) [39,66,67] | Inhibiting the recruitment and activation of inflammatory cell, suppressing the apoptosis of T cells and increasing perforin and granzyme B production |
| Colchicine [41] | Suppressing the activation of inflammasome and the formation of microtubule | |
| TNF-α | TNF-α blockers [73] and anti-TNF-α [72,74] | Decreasing the expression of inflammatory mediators and adhesion molecules |
| Colchicine [41] | Suppressing the activation of inflammasome and the synthesis of TNF-α | |
| Il-1β | Anakinra (IL-1ra) [79,80,81] | Preventing the recruitment and activation of immune inflammatory cell and decreasing vascular permeability and leakage |
| IL-18 | Tadekinig-α (nIL-18P) [87] and rIL-18BP [88] | Suppressing the activation of T and NK cells and the production of IFN-γ |
| GM-CSF | Namilumab, mavrilimumab and otilimab [31] | Inhibiting the recruitment and activation of neutrophils |
| IL-7 | rIL-7 [83,137] | Promoting the expansion of lymphocytes, inhibiting apoptosis, reversal of T cell exhaustion, and expression of cell adhesion molecules |
| CCR2 | siRNA-mediated silencing of CCR2 [107] | Decreasing macrophage recruitment to the sites of inflammation |
| NK cell | CYNK-001 [120] | Direct killing of infected cells and the induction of immune responses |
| anti-SARS-CoV-2 mAbs | CP [144,145,146], IVIg [147,148,150], anti-RBD nAb [140,151,152], ACE2-Fc and RBD-Fc fusions [155], anti- SARS-CoV-2 scFv [156] | Blocking the fusion, entry, and replication of the coronavirus |
ACE, angiotensin-converting enzyme; Ang, angiotensin; AT1R, Ang II receptor type 1; C3a/C5a, complement proteins, CCR, chemokine (C-C motif) ligand receptor; CP, convalescent plasma; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; IVIg, intravenous immunoglobulin, mAb, monoclonal antibody; MUC, mucin; RBD, receptor-binding domain; rIL-7, recombinant IL-7; rIL-18BP, recombinant IL-18 binding protein; rhACE2-Fc fusion proteins, recombinant human ACE2-Fc fusion proteins; rhIL-1ra, recombinant human IL-1α; scFv, single-chain variable fragment; srhACE2, soluble recombinant human; SP, surfactants; SYK, spleen tyrosine kinase; Th, helper T cell; TNF, tumor necrosis factor.