The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), appears with a wide spectrum of mild-to-critical clinical complications. Many clinical and experimental findings suggest the role of inflammatory mechanisms in the immunopathology of COVID-19. Hence, cellular and molecular mediators of the immune system can be potential targets for predicting, monitoring, and treating the progressive complications of COVID-19. In this review, we assess the latest cellular and molecular data on the immunopathology of COVID-19 according to the pathological evidence (e.g., mucus and surfactants), dysregulations of pro- and anti-inflammatory mediators (e.g., cytokines and chemokines), and impairments of innate and acquired immune system functions (e.g., mononuclear cells, neutrophils and antibodies). Furthermore, we determine the significance of immune biomarkers for predicting, monitoring, and treating the progressive complications of COVID-19. We also discuss the clinical importance of recent immune biomarkers in COVID-19, and at the end of each section, recent clinical trials in immune biomarkers for COVID-19 are mentioned.
【저자키워드】 COVID-19, Cytokine storm, Biomarker, lung, immunopathology, RBD, receptor-binding domain, complications, BEC, Bronchial epithelial cell, TMPRSS2, Transmembrane serine protease 2, SARS-CoV, severe acute respiratory syndrome coronavirus, N, nucleocapsid, IFN, interferon, JAK, Janus kinase, ARDS, acute respiratory distress syndrome, GM-CSF, granulocyte-macrophage colony-stimulating factor, IL, interleukin, MCP, monocyte chemoattractant protein, MERS, Middle East respiratory syndrome, CRP, C-reactive protein, WBC, White blood cell, COVID-19, coronavirus disease-2019, IVIG, intravenous immunoglobulin, DIC, disseminated intravascular coagulation, CP, convalescent plasma, NK, natural killer, TGF, Transforming growth factor, CRS, Cytokine release syndrome, CQ, Chloroquine, HCQ, hydroxychloroquine, LDH, lactate dehydrogenase, ESR, Erythrocyte sedimentation rate, HLH, Hemophagocytic lymphohistiocytosis, LAG-3, Lymphocyte-activation gene 3, RA, Rheumatoid arthritis, VEGF, Vascular endothelial growth factor, NSP, Non-structural Proteins, NTD, N Terminal Domain, nAb, Neutralizing Antibody, TLR, Toll like Receptor, PRR, Pattern Recognition Receptors, APC, Antigen-Presenting Cell, HLA, human leukocyte antigen, mAb, monoclonal antibody, ACE, angiotensin-converting enzyme, CCL, chemokine (C-C motif) ligand, aPTT, activated partial thromboplastin time, Ang, angiotensin, CT, Computerized Tomography, BALF, bronchoalveolar lavage fluid, siRNA, small interfering RNA, IFITM, Interferon-induced transmembrane protein, NLR, neutrophil-to-lymphocyte ratio, CXCL, Chemokine (C-X-C motif) ligand, ssRNA, single-stranded RNA, Th, helper T cell, ChiCTR, Chinese Clinical Trial Registry, MOF, Multiple organ failure, CTL, cytotoxic T lymphocyte, PD1, programmed cell death protein 1, dsRNA, double-stranded RNA, ACEI, ACE inhibitor, AAK-1, activated protein (AP) 2 associated kinase 1, Ab, antibody, AEC, alveolar epithelial cells, AICD, activation-induced cell death, ARB, Ang II receptor blocker, AT1R, Ang II receptor type 1, BTK, Bruton tyrosine kinase, C3 and C5, complement proteins, CCR, chemokine (C-C motif) ligand receptor, C-GAS-STING, cGAMP binds to stimulator of interferon genes, CXCR, chemokine (C-X-C motif) ligand receptor, FcγR, Fc gamma receptor, Fio2, fraction of inspired oxygen, GAK, G-associated kinase, GzmB, granzyme B, HR-2, heptad repeat region-2, ICU, admissions to intensive care units, IP-10, interferon (IFN)-γ inducible protein-10, IRF-1, IFN regulatory factor 1, ISG, induction of IFN-stimulated gene, JUN, c-Jun N-terminal kinases, KL-6, Krebs von den Lungen-6, LWR, lymphocyte-to-WBCs ratio, LY6E, lymphocyte antigen 6 family member E, MDA-5, melanoma differentiation-associated protein-5, MIP, macrophage inflammatory proteins, MUC, mucin, NCT, clinicaltrials.gov identifier, NFkB, nuclear factor kappa-light-chain-enhancer of activated B cells, NKRF, NFkB repressing factor, NLRP3, nod-like receptor protein 3, ORF-1ab, open reading frame 1ab, Pao2, partial pressure of oxygen, PCT, procalcitonin, PKR, protein kinase R, PLR, platelet-to-lymphocyte ratios, PT, prothrombin time, RAS, regulator of the renin-angiotensin system, rBP-C33Leu, recombinant surfactant protein C analogue, rhACE2-Fc fusion proteins, recombinant human ACE2-Fc fusion proteins, rhIL-1ra, recombinant human IL-1 receptor, RIG, retinoic acid-inducible gene-I, rIL7, recombinant IL-7, RLR, RIG-I-like receptors, RT-qPCR, real time-quantitative PCR, S1PR, sphingosine-1-phosphate receptors, SAA, serum amyloid A, SARS, severe acute respiratory, scFv, single-chain variable fragment, SP, surfactant, SPo2, arterial oxygen saturation, S-protein, spike-protein, srhACE2, soluble recombinant human (srh)ACE2, TIM-3, T-cell immunoglobulin mucin 3, TNF-α, tumor necrosis factor, Treg, regulatory T cells,