Table I.
| Gene symbol | Gene name | Main function with brief description (Refs.) | Figure(s) | Entitya |
|---|---|---|---|---|
| ACE2 | Angiotensin I converting enzyme 2 | Transmembrane protein-entry point of SARS-CoV-2 (22-24,28) | 3 | C |
| ADAM10 | ADAM metallopeptidase domain 10 | Sheddase with strong specificity for peptide hydrolysis reactions (68-70) | 3 | T |
| ADAM17 | ADAM metallopeptidase domain 17 | Sheddase triggering release of cytokines receptors, ligands, etc. (68,69,71) | 3,4 | V, T |
| ADAMTS13 | ADAM metallopeptidase with throm bospondin type 1 motif 13 | Enzyme that cleaves von Willebrand factor (68,69) | 3,4 | V, T |
| ADRA2C | Adrenoceptor alpha 2C | Mediators in catecholamine-induced inhibition of adenylate cyclase through the action of G proteins (72) | 3 | C |
| ADRB1 | Adrenoceptor beta 1 | Renin release/lipolysis/Increases heart rate with chrono/inotropic effect (73) | 3 | C |
| ADRB2 | Adrenoceptor beta 2 | Facilitating respiration (74) | 3 | C |
| AGER | Advanced glycosylation end-product specific receptor | Mediates interactions of advanced glycosylation end products (75) | 3 | C |
| AIM2 | Interferon-inducible protein AIM2 | AIM2 inflammasome plays a crucial role in the defense against viral infection (76) | 3 | C, T |
| ANGPT1 | Angiopoietin 1 | Receptor of advanced glycosylation end products of proteins, mediating amyloid beta peptide effect on neurons and microglia (77) | 3 | C |
| ANGPT2 | Angiopoietin 2 | Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling (78) | 3 | C |
| AURKA | Serine/threonine-protein kinase 6 | Orchestrate an exit from mitosis by contributing to the completion of cytokinesis the process through which the cytoplasm of the parent cell is split into two daughter cells (79) | 4 | V |
| C4B | Complement C4B (Chido blood group) | Mediator of local inflammatory process, inducing the contraction of smooth muscle, increasing vascular permeability and causing histamine release from mast cells and basophilic leukocytes (80) | 3,4 | V, T |
| C5 | Complement C5 | Involved in the complement system (81) | 3,4 | V, T |
| C6 | Complement C6 | Causes cell lysis (82) | 3,4 | V, T |
| C7 | Complement C7 | Creates a hole on pathogen surfaces leading to cell lysis (82) | 3,4 | V, T |
| C9 | Complement C9 | Cell lysis and death contributor (82) | 3,4 | V, T |
| CASP1 | Caspase 1 | Inflammatory response initiator (83) | 3,4 | C, V |
| CASP10 | Caspase 10 | Cell apoptosis (84) | 3 | C |
| CASP9 | Caspase 9 | Innate immunity, mitochondrial apoptosis (85) | 3 | C |
| CCL2 | C-C motif chemokine ligand 2 | Induces a strong chemotactic response and mobilization of intracellular calcium ions (86,87) | 3 | C |
| CCL3 | Chemokine (C-C motif) ligand 3 | Pyrogenic, attracting macrophages, monocytes and neutrophils (88) | 3 | C |
| CCN2 | Cellular communication network factor 2 | Cell adhesion, apoptosis, migration, proliferation, differentiation, apoptosis, survival and senescence (89) | 3 | C |
| CD3D | CD3d molecule | Cell differentiation and adaptive immune response (90) | 3 | C |
| CD3E | CD3e molecule | Cell differentiation and adaptive immune response (90) | 3 | C |
| CD3G | CD3g molecule | Cell differentiation and adaptive immune response (90) | 3 | C |
| CD4 | CD4 molecule | Cell differentiation and adaptive immune response (91) | 3 | C |
| CD40LG | CD40 ligand | Acts as a ligand for integrins which have cell-type dependent effects, such as B-cell activation, NF-κB signaling and anti-apoptotic signaling (92,93) | 3 | T |
| CD8A | CD8a molecule | Multiple functions in responses against both ex/internal offenses (91) | 3 | C, T |
| CD19 | B-lymphocyte antigen CD19 | Decreases B-cell receptor pathways (94,95) | 4 | V |
| CD40LG | Cluster of differentiation 40 | Mediates many immune and inflammatory responses including T-cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation (96) | 3,4 | T, V |
| CD46 | CD46 complement regulatory protein | Activates T-lymphocytes following vaccination (97,98) | 4 | V |
| CDC20 | Cell division cycle 20 | Regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in post-mitotic neurons; Cdc20-apc/ c-induced degradation of neurod2 induces presynaptic differentiation (91) | 3,4 | V, T |
| CDCA3 | Cell division cycle associated 3 | Involves in protein ubiquitination (99) | 3,4 | V, T |
| CRP | C-reactive protein | Mitotic initiator (100) | 3 | C |
| CSF1R | Colony stimulating factor 1 receptor | Controls the production, differentiation, and function macrophages (93,101) | 3,4 | V, T |
| CSF2 | Colony stimulating factor 2 | Cytokine affecting mostly eosinophils and macrophages (102) | 3,4 | V, T |
| CXCL10 | C-X-C motif chemokine ligand 10 | Chemoattraction for T- and NK cells, monocytes (87,93,103,104) | 3 | C |
| CXCL8 | C-X-C motif chemokine ligand 8 | Neutrophil chemotactic factor increasing respiratory burst (87,105) | 3,4 | C, V |
| CYP11B2 | Cytochrome P450 family 11 subfamily B member 2 | Aldosterone synthesis (87,106) | 3 | C |
| CYP2C19 | Cytochrome P450 family 2 subfamily C member 19 | Part of cytochrome P450, involved in drug and lipid metabolism (107) | 3 C | |
| CYP2C9 | Cytochrome P450 family 2 subfamily C member 9 | Part of cytochrome P450, involved in drug and lipid metabolism (107) | 3 C | |
| DDX58 | Retinoic acid-inducible gene I | Activates interferon and cytokines production after viral infection (108) | 3 | C |
| EDN1 | Endothelin 1 | Potent vasoconstrictor (106,109) | 3 | C |
| EPO | Erythropoietin | Stimulation of erythropoiesis, vasoconstriction, angiogenesis (106) | 3,4 | V, T |
| F2 | Coagulation factor II, thrombin | Activates the coagulation cascade inhibition (110) | 3,4 | V, T |
| FCGR1A | Fc fragment of IgG receptor Ia | Complex activation or inhibitory effects on cell functions (111) | 3,4 | V, T |
| FCGR1B | Fc fragment of IgG receptor Ib | Humoral immune response (112) | 3,4 | V, T |
| FCGR2A | Fc fragment of IgG receptor IIa | Humoral immune response to pathogens, phagocytosis of opsonized antigens (113) | 3,4 | V, T |
| FCGR2B | Fc fragment of IgG receptor IIb | Phagocytosis of immune complexes and regulation of antibody production (114) | 3,4 | V, T |
| FCGR3A | Fc fragment of IgG receptor IIIa | Mediates antibody-dependent cellular cytotoxicity and phagocytosis (115) | 3,4 | V, T |
| FCGR3B | Fc fragment of IgG receptor IIIb | Captures immune complexes in the peripheral circulation (116) | 3,4 | V, T |
| FGF7 | Fibroblast growth factor 7 | Cell growth, morphogenesis and tissue repair (117) | 3,4 | C, V |
| FKBP1A | FKBP prolyl isomerase 1A | Immunoregulation and basic cellular processes involving protein folding and trafficking (118) | 3,4 | V, T |
| FN1 | Fibronectin 1 | Cell growth, morphogenesis and tissue repair (70) | 3 | C |
| FOS | Fos proto-oncogene, AP-1 transcription factor subunit | Signal transduction, cell proliferation and differentiation (119) | 3 | C |
| GNB3 | G protein subunit beta 3 | Integrates signals between receptor and effector proteins (120) | 3 | C |
| GZMA | Granzyme A | Common component necessary for lysis of target cells by cytotoxic T-lymphocytes and natural killer cells (24) | 3 | C |
| GZMB | Granzyme B | Recognize specific infected target cells (121) | 3 | C |
| GZMH | Granzyme H | Suppresses viral replication (122) | 3 | C |
| HLA-A | Major histocompatibility complex, class I, A | Sole link between the immune system and what happens inside cells (123) | 3,4 | C, V |
| HLA-B | Major histocompatibility complex, class I, B | Helps the immune system distinguish the endo-from exogenous proteins (123) | 3,4 | C, V |
| HLA-DRB1 | HLA class II histocompatibility antigen, DRB1 beta chain | Triggers response to viral infections (41) | 3,4 | C, V, T |
| ICAM1 | Intercellular adhesion molecule 1 | Signal transduction (92,93) | 3,4 | V, T |
| IFI16 | Interferon gamma inducible protein 16 | Recognizes RNA viral infection, enhancing DDX58 production (124) | 3 | C, T |
| IFNA1 | Interferon alpha 1 | Antiviral and immunomodulator (125) | 3 | C |
| IFNG (IFN-γ) | Interferon gamma | Antiviral antibacterial and immunomodulatory effects (104) | 3,4 | V, T |
| IFNL1 | Interferon lambda 1 | Antiviral antibacterial and immunomodulatory effects (126) | 3 | C |
| IFNL2 | Interferon lambda 2 | Antiviral antibacterial and immunomodulatory effects (126) | 3 | C |
| IFNL3 | Interferon lambda 3 | Antiviral antibacterial and immunomodulatory effects (126) | 3 | C |
| IFNLR1 | Interferon lambda receptor 1 | Antiviral antibacterial and immunomodulatory effects (126) | 3 | C |
| IKBKG | Inhibitor of nuclear factor kappa B kinase regulatory subunit gamma | Antiviral activity through JAK/STAT signaling activation (127) | 3 | C |
| IL10 | Interleukin 10 | Multiple, pleiotropic effects in immunoregulation, limits excessive infected tissue disruption (92) | 3 | C |
| IL10RB | Interleukin 10 receptor subunit beta | JAK1 and STAT2-mediated phosphorylation of STAT3 (128) | 3 | C |
| IL12A | Interleukin 12A | Induces IFNG (92) | 3 | C |
| IL12B | Interleukin 12B | Induces IFNG by resting PBMC (92) | 3 | C |
| IL17A | Interleukin 17A | Mediates protective innate immunity to pathogens or contributes to pathogenesis of inflammatory diseases (87) | 3 | C |
| IL18 | Interleukin 18 | Potent inducer of inflammatory cytokines, especially IFNG (129) | 3 | C |
| IL1A | Interleukin 1 alpha | Promotion of intimal inflammation, fever, sepsis and atherogenesis (41) | 3 | C |
| IL1B | Interleukin 1 beta | Promotion of fever, development of diabetes mellitus, apoptosis of pancreatic β-cells (87,105) | 3,4 | C, V, T |
| IL1RAP | Interleukin 1 receptor accessory protein | Induces synthesis of acute phase and proinflammatory proteins during infection, tissue damage, or stress (130) | 3 | C |
| IL3 | Interleukin 3 | Growth and differentiation of hematopoietic progenitor cells regulator and functional activator of mature neutrophils or macrophages (131) | 3,4 | V, T |
| IL33 | Interleukin 33 | Gene transcription regulator, released after cell necrosis triggering immune response and stress (132) | 3 | C |
| IL36G | Interleukin 36 gamma | Inflammasome dependent, involved in systemic inflammation (133) | 3 | C |
| IL4 | Interleukin 4 | Hematopoiesis, antibody production, inflammation response (117) | 3,4 | V, T |
| IL5 | Interleukin 5 | Eosinophil migration, activation survival (134) | 3,4 | V, T |
| IL6 | Interleukin 6 | Innate and adaptive immune response to infections (135) | 3,4 | C, V, T |
| INS | Insulin | Blood sugar regulator (136) | 3 | C |
| ITGA2B | Integrin subunit alpha 2b | Coagulation (137,138) | 3,4 | V, T |
| JAK1 | Janus kinase 1 | Cell growth survival, development differentiation of various cell types (139) | 3 | C |
| JAK2 | Janus kinase 2 | Cell growth and proliferation (139) | 3 | C, T |
| JUN | Jun proto-oncogene, AP-1 transcription factor subunit | Gene expression regulator (92) | 3 | C |
| KCNE1 | Potassium voltage-gated channel subfamily E regulatory subunit 1 | Potassium channels regulator (140,141) | 3 | C |
| KCNH2 | Potassium voltage-gated channel subfamily H member 2 | Electrical signals transmission (141) | 3 | C |
| KCNJ2 | Potassium inwardly rectifying channel subfamily J member 2 | Muscle movement (heart or skeletal) (142) | 3 | C |
| KCNQ1 | Potassium voltage-gated channel subfamily Q member 1 | Electrical signals generation and transmission (143) | 3 | C |
| LCN2 | Lipocalin 2 | Sequesters iron and preventing its use by bacteria, thus limiting their growth (144) | 3 | C |
| MMP1 | Matrix metallopeptidase 1 | Degrades collagen type I and II (145,146) | 3 | C |
| MMP2 | Matrix metallopeptidase 2 | Extracellular matrix (146) | 3 | C |
| MPL | MPL proto-oncogene, thrombopoietin receptor | Proliferator of cells involved in blood clotting (147) | 3,4 | V, T |
| MS4A1 | Membrane spanning 4-domains A1 | Regulator of cellular calcium influx necessary for the B-lymphocytes activation (148) | 3,4 | C, V |
| MS4A3 | Membrane spanning 4-domains A3 | Marker of immature circulating neutrophils, a cellular population associated to COVID-19 severe disease (148) | 3 | C |
| MUC1 | Mucin 1, cell surface associated | High viscosity of airway mucus and sputum retention in the small airway of COVID-19 patients (149) | 3 | C |
| MYD88 | MYD88 innate immune signal transduction adaptor | Initiates early immune responses (150) | 3 | C |
| NCAM1 | Neural cell adhesion molecule 1 | Molecular mimicry between NCAM-1 and the SARS-CoV-2 envelope protein (151) | 3 | C, T |
| NFAT5 | Nuclear factor of activated T-cells 5 | Protects cells against harmful effects of stress (137) | 3 | C |
| NFATC1 | Nuclear factor of activated T-cells 1 | Transcription factor (137) | 3,4 | C, V |
| NFATC2 | Nuclear factor of activated T-cells 2 | Neuroinflammatory factor (137) | 3 | C |
| NFATC3 | Nuclear factor of activated T-cells 3 | Involved in proliferation of human pulmonary fibroblasts after hypoxic stimulus (137) | 3 | C |
| NFATC4 | Nuclear factor of activated T-cells 4 | Transcriptional regulator in naive T-cells and differentiated effector T-cells, dependent on calcium/PLCγ/calmodulin/calcineurin signaling (137) | 3 | C |
| NFKB1 | Nuclear factor kappa B subunit 1 | Activated by various intra/extra-cellular stimuli as viruses (92) | 3,4 | C, V |
| NLRP3 | NLR family pyrin domain containing 3 | Intracellular sensor that detects a broad range of pathogen motifs (59) | 3,4 | C, V |
| NOD2 | Inflammatory bowel disease protein 1 | Activates NFKB1, negatively regulates TLR2 (152,153) | 3 | C, T |
| NOS1 | Nitric oxide synthase 1 | Chemical messenger (154,155) | 3 | C |
| NOS1AP | Nitric oxide synthase 1 adaptor protein | Inhibitor of Nnos (156) | 3 | C |
| NOS3 | Nitric oxide synthase 3 | Regulating vascular tone, cellular proliferation leucocyte adhesion and platelet aggregation (157,158) | 3 | C |
| NTRK1 | Neurotrophic receptor tyrosine kinase 1 | Development and survival of neurons (159) | 3,4 | V, T |
| NTRK2 | Neurotrophic receptor tyrosine kinase 2 | Development and maturation of the central and the peripheral nervous systems (159) | 3,4 | V, T |
| NTRK3 | Neurotrophic receptor tyrosine kinase 3 | Development of heart and nervous (159) | 3,4 | V, T |
| OLFM4 | Olfactomedin 4 | Facilitates cell adhesion, most probably through interaction with cell surface lectins and cadherin (160) | 3 | C |
| P2RX1 | Purinergic receptor P2X 1 | Ligand-gated ion channel with relatively high calcium permeability (161) | 3 | C |
| P2RX7 | Purinergic receptor P2X 7 | Receptor for ATP that acts as a ligand-gated ion channel (162) | 3,4 | C, V |
| PDGFA | Platelet derived growth factor subunit A | Wound healing (163) | 3 | C |
| PECAM1 | Platelet and endothelial cell adhesion molecule 1 | Cell adhesion (164) | 3 | C |
| PLAUR | Plasminogen activator, urokinase receptor | Localizing and promoting plasmin formation (165) | 3 | C |
| PPP3CB | Protein phosphatase 3 catalytic subunit beta | Transduction of intracellular Ca(2+)-mediated signals (166) | 3 | C |
| PRF1 | Perforin 1 | Defense against virus-infected cells (122) | 3 | C |
| PTGS2 | Prostaglandin-endoperoxide synthase 2 | Role in the inflammatory response (167) | 3 | C |
| PTPN11 | Protein tyrosine phosphatase non-receptor type 11 | Positively regulates MAPK signal transduction pathway (168,169) | 3 | C |
| PYCARD | PYD and CARD domain containing | Key mediator in apoptosis and inflammation (170,171) | 3,4 | C, V |
| REN | Renin | Angiotensin I from angiotensinogen generator in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney (172,173) | 3 | C |
| SCL11A2 | Natural resistance-associated macrophage protein 2 | Important in metal transport and their insertion into mitochondria (174) | 3,4 | V, T |
| SCN5A | Sodium voltage-gated channel alpha subunit 5 | Responsible for the initial upstroke of the action potential in an electrocardiogram (175) | 3 | C |
| SELE | Selectin E | Immunoadhesion (176) | 3,4 | V, T |
| SELP | Selectin P | Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with SELPLG (177) | 3,4 | V, T |
| SERPINE1 | Serpin family E member 1 | Alveolar type 2 cells senescence in the lung (178) | 3 | C, T |
| SERPINE2 | Serpin family E member 2 | Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase (40) | 3 | C |
| SFTPC | Surfactant protein C | Lowering the surface tension at the air-liquid interface in the peripheral air spaces (179) | 3 | C |
| SFTPD | Surfactant protein D | May participate in the extracellular reorganization or turnover of pulmonary surfactant, regulates immune response (180) | 3 | C |
| SHC1 | SHC adaptor protein 1 | Signaling adapter that couples activated growth factor receptors to signaling pathways (181) | 3 | T |
| SIGIRR | Single Ig and TIR domain containing | Inflammation immune, response modulator (182) | 3 | C |
| SLC11A2 | Solute carrier family 11-member 2 | Metal transporter (183) | 3 | T |
| SOCS1 | Suppressor of cytokine signaling 1 | Exerts the viral virulence effect via inhibition of type I and type II interferon (IFN) function (184) | 3,4 | V, T |
| STXBP2 | Syntaxin binding protein 2 | Involved in cytolytic pathway (185) | 3 | T |
| TBK1 | TANK binding kinase 1 | Regulator of inflammatory responses to foreign agents (186) | 3 | C |
| TF | Transferrin | Transports of iron from sites of absorption and heme degradation to those of storage and utilization (187) | 3,4 | V, T |
| TFPI | Tissue factor pathway inhibitor | Anticoagulant protein blocking the initiation of blood coagulation by inhibiting TF-f VIIa and early forms of prothrombinase (188) | 3,4 | V, T |
| TFRC | Transferrin receptor | Erythropoiesis and neurologic development (189) | 3,4 | V, T |
| TGFB1 | Transforming growth factor beta 1 | Gene expression proliferation (70) | 3 | C, T |
| THPO | Thrombopoietin | Regulates platelets and macrophages differentiation (190) | 3,4 | V, T |
| TICAM1 | Toll-like receptor adaptor molecule 1 | Native immunity against invading pathogens (191) | 3 | C |
| TLR2 | Toll-like receptor 2 | Pathogen recognition-potential therapeutic target (192-194) | 3 | C, T |
| TLR4 | Toll-like receptor 4 | Upregulated after SARS-CoV-2 infection (195) | 3 | C |
| TNF | Tumor necrosis factor | Biomarker of COVID-19 severity (104) | 3,4 | C, V, T |
| TNFRSF1A | TNF receptor superfamily member 1A | Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase (93,104) | 3 | C |
| TNFRSF1B | TNF receptor superfamily member 1B | Regulates TNF-α function by antagonizing its biological activity (93,104) | 3 | C |
| TRAF3 | TNF receptor associated factor 3 | Regulates pathways leading to a NFKB and MAP kinases activation, and B-cell survival (196) | 3 | C |
| TYK2 | Tyrosine kinase 2 | Antiviral activity (197) | 3 | C |
| VCAM1 | Vascular cell adhesion molecule 1 | Mediates the adhesion of lymphocytes, monocytes, eosinophils and basophils to vascular endothelium (198) | 3,4 | V, T |
| VEGFA | Vascular endothelial growth factor A | Dominant inducer to blood vessels growth (increases their permeability) (199) | 3 | C |
| VKORC1 | Vitamin K epoxide reductase complex subunit 1 | Reduces inactive vitamin K 2,3-epoxide to active vitamin K (200) | 3 | C |
| VWF | von Willebrand factor | Involved in hemostasis and thrombosis (201) | 3,4 | C, V, T |
a
Entities: C, COVID-19; V, vaccine-induced thrombotic thrombocytopenia; T, thrombocytopenia.