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Cytokine storm in the pathophysiology of COVID-19: possible functional disturbances of miRNAs
review-article
21 September 2021
SARS-CoV-2,
COVID-19,
miRNAs,
Gene regulators,
Cytokine storm,
miRNAs-based therapy,
2019-nCoV, 2019 novel coronavirus,
3'-UTR, 3'-untranslated region,
AA, Arachidonic acid,
ACE, Angiotensin-converting enzyme,
ADAM17, A disintegrin and metalloproteinase 17,
AGEs, Advanced glycation end products,
AGO, Argonaute,
ALI, Acute lung injury,
Amp, Amplifier,
Ang, Angiotensin,
ANRIL, Antisense noncoding RNA in the INK4 locus,
AP-1, Activator protein 1,
APJ, Apelin receptor,
ARDS, Acute respiratory distress syndrome,
ASOs, Antisense oligonucleotides,
AT1R, Ang II receptor type 1,
BBB, Blood-brain barrier,
CatB/L, Cathepsin B/L,
CCL, C-C motif chemokine ligand,
CD, Cluster of differentiation,
ceRNAs, Competing endogenous RNAs,
CHD, Coronary heart disease,
circRNAs, Circular RNAs,
CNS, Central nervous system,
COVID-19, Coronavirus disease 2019,
COX, Cyclooxygenase,
cPLA2, Cytoplasmic phospholipase A2,
CRISPR, Cas13 family of clustered regularly interspaced short palindromic repeats,
CSF, Colony-stimulating factor,
CXCL, C-X-C motif chemokine ligand,
CYLD, Cylindromatosis,
DAMPs, Damage-associated molecular patterns,
DCs, Dendritic cells,
DIC, Disseminated intravascular coagulation,
DMD, Dense matted deposits,
DMVs, Double membrane vesicles,
E protein, Envelope protein,
EAE, Experimental autoimmune encephalomyelitis,
ER, Endoplasmic reticulum,
ERK, Extracellular signal-regulated kinase,
FOXO3, Forkhead box O3,
G-CSF, Granulocyte CSF,
GM-CSF, Granulocyte-macrophage CSF,
gp130, Glycoprotein 130,
H3, Histone 3,
HMGB1, High mobility group box protein 1,
hsa, Homo sapiens,
HSP, Heat shock protein,
ICU, Intensive care unit,
IFN, Interferon,
IFNs-I, Type I IFNs,
Ig, Immunoglobulin,
IκB-ζ, Inhibitor of nuclear factor kappa B zeta,
IL, Interleukin,
IRF, IFN regulatory factor,
ISGs, IFN-stimulated genes,
JAK, Janus kinase,
K, Lysine,
KCNQ1OT1, KCNQ1 overlapping transcript 1,
lncRNAs, Long non-coding RNAs,
LOXs, Lipoxygenases,
LPLs, Lysophospholipids,
LPS, Lipopolysaccharide,
LTs, Leukotrienes,
M protein, Membrane protein,
MAPK, Mitogen-activated protein kinase,
MCs, Mast cells,
M-CSF, Macrophage CSF,
MDA5, Melanoma differentiation-associated protein 5,
me2, Dimethylation,
me3, Trimethylation,
MEG3, Maternally expressed gene 3,
MERS-CoV, Middle East respiratory syndrome coronavirus,
mIL-6R, Membrane IL-6 receptor,
miRISC, MicroRNA-induced silencing complex,
miRNAs, MicroRNAs,
MMP, Matrix metalloproteinase,
MODS, Multiple organ dysfunction syndrome,
mPGES-1, Microsomal prostaglandin E synthase-1,
mRNA, Messenger RNA,
MyD88, Myeloid differentiation factor 88,
N protein, Nucleocapsid protein,
NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells,
NLRP3, NOD-, LRR- and pyrin domain-containing protein 3,
NOXs, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases,
nsp, Non-structural protein,
ORF, Open reading frame,
OxPLs, Oxidized phospholipids,
PaO2/FiO2, Pressure of arterial oxygen to fractional inspired oxygen concentration,
PBMCs, Peripheral blood mononuclear cells,
PG, Prostaglandin,
PKCα, Protein kinase C alpha,
PPP2CA, Protein phosphatase 2 catalytic subunit alpha,
pre-miRNAs, Precursor miRNAs,
pri-miRNAs, Primary miRNAs,
PRR, Pattern recognition receptor,
RAGE, Receptor for advanced glycation end products,
RAS, Renin-Angiotensin system,
RBCs, Red blood cells,
RGMB-AS1, RGMB antisense RNA 1,
RhoB, Ras homolog gene family member B,
RIG-I, Retinoic acid-inducible gene I,
RNAi, RNA interference,
RNA pol, RNA polymerase,
ROS, Reactive oxygen species,
S100A9, S100 calcium-binding protein A9,
S protein, Spike protein,
SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2,
sIL-6R, Soluble IL-6R,
siRNAs, Small interfering RNAs,
SOCS3, Suppressor of cytokine signaling 3,
SOFA, Sequential organ failure assessment score,
Sry, Sex-determining region Y,
STAT, Signal transducer and activator of transcription,
TAB, Transforming growth factor β-activated kinase-1 (TAK1)-binding protein,
TBK1, TANK-binding kinase 1,
Th cells, T helper cells,
TIMP-I, Tissue inhibitors of matrix metalloproteinases-I,
TLRs, Toll-like receptors,
TMPRSS2, Transmembrane serine protease 2,
TNF-α, Tumor necrosis factor alpha,
TNFR, TNF receptor,
TRIM27, Tripartite motif-containing protein 27,
TXs, Thromboxanes,
v-miRNA, Viral miRNA,
XPO5, Exportin-5
There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
SARS-CoV-2, as the causative agent of COVID-19, is an enveloped positives-sense single-stranded RNA virus that belongs to the Beta-CoVs sub-family. A sophisticated hyper-inflammatory reaction named cytokine storm is occurred in patients with severe/critical COVID-19, following an imbalance in immune-inflammatory processes and inhibition of antiviral responses by SARS-CoV-2, which leads to pulmonary failure, ARDS, and death. The miRNAs are small non-coding RNAs with an average length of 22 nucleotides which play various roles as one of the main modulators of genes expression and maintenance of immune system homeostasis. Recent evidence has shown that Homo sapiens (hsa)-miRNAs have the potential to work in three pivotal areas including targeting the virus genome, regulating the inflammatory signaling pathways, and reinforcing the production/signaling of IFNs-I. However, it seems that several SARS-CoV-2-induced interfering agents such as viral (v)-miRNAs, cytokine content, competing endogenous RNAs (ceRNAs), etc. preclude efficient function of hsa-miRNAs in severe/critical COVID-19. This subsequently leads to increased virus replication, intense inflammatory processes, and secondary complications development. In this review article, we provide an overview of hsa-miRNAs roles in viral genome targeting, inflammatory pathways modulation, and IFNs responses amplification in severe/critical COVID-19 accompanied by probable interventional factors and their function. Identification and monitoring of these interventional elements can help us in designing the miRNAs-based therapy for the reduction of complications/mortality rate in patients with severe/critical forms of the disease.
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Most cited references214
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
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Author and article information
sars-cov-2,covid-19,mirnas,gene regulators,cytokine storm,mirnas-based therapy,2019-ncov, 2019 novel coronavirus,3'-utr, 3'-untranslated region,aa, arachidonic acid,ace, angiotensin-converting enzyme,adam17, a disintegrin and metalloproteinase 17,ages, advanced glycation end products,ago, argonaute,ali, acute lung injury,amp, amplifier,ang, angiotensin,anril, antisense noncoding rna in the ink4 locus,ap-1, activator protein 1,apj, apelin receptor,ards, acute respiratory distress syndrome,asos, antisense oligonucleotides,at1r, ang ii receptor type 1,bbb, blood-brain barrier,catb/l, cathepsin b/l,ccl, c-c motif chemokine ligand,cd, cluster of differentiation,cernas, competing endogenous rnas,chd, coronary heart disease,circrnas, circular rnas,cns, central nervous system,covid-19, coronavirus disease 2019,cox, cyclooxygenase,cpla2, cytoplasmic phospholipase a2,crispr, cas13 family of clustered regularly interspaced short palindromic repeats,csf, colony-stimulating factor,cxcl, c-x-c motif chemokine ligand,cyld, cylindromatosis,damps, damage-associated molecular patterns,dcs, dendritic cells,dic, disseminated intravascular coagulation,dmd, dense matted deposits,dmvs, double membrane vesicles,e protein, envelope protein,eae, experimental autoimmune encephalomyelitis,er, endoplasmic reticulum,erk, extracellular signal-regulated kinase,foxo3, forkhead box o3,g-csf, granulocyte csf,gm-csf, granulocyte-macrophage csf,gp130, glycoprotein 130,h3, histone 3,hmgb1, high mobility group box protein 1,hsa, homo sapiens,hsp, heat shock protein,icu, intensive care unit,ifn, interferon,ifns-i, type i ifns,ig, immunoglobulin,iκb-ζ, inhibitor of nuclear factor kappa b zeta,il, interleukin,irf, ifn regulatory factor,isgs, ifn-stimulated genes,jak, janus kinase,k, lysine,kcnq1ot1, kcnq1 overlapping transcript 1,lncrnas, long non-coding rnas,loxs, lipoxygenases,lpls, lysophospholipids,lps, lipopolysaccharide,lts, leukotrienes,m protein, membrane protein,mapk, mitogen-activated protein kinase,mcs, mast cells,m-csf, macrophage csf,mda5, melanoma differentiation-associated protein 5,me2, dimethylation,me3, trimethylation,meg3, maternally expressed gene 3,mers-cov, middle east respiratory syndrome coronavirus,mil-6r, membrane il-6 receptor,mirisc, microrna-induced silencing complex,mirnas, micrornas,mmp, matrix metalloproteinase,mods, multiple organ dysfunction syndrome,mpges-1, microsomal prostaglandin e synthase-1,mrna, messenger rna,myd88, myeloid differentiation factor 88,n protein, nucleocapsid protein,nf-κb, nuclear factor kappa-light-chain-enhancer of activated b cells,nlrp3, nod-, lrr- and pyrin domain-containing protein 3,noxs, nicotinamide adenine dinucleotide phosphate (nadph) oxidases,nsp, non-structural protein,orf, open reading frame,oxpls, oxidized phospholipids,pao2/fio2, pressure of arterial oxygen to fractional inspired oxygen concentration,pbmcs, peripheral blood mononuclear cells,pg, prostaglandin,pkcα, protein kinase c alpha,ppp2ca, protein phosphatase 2 catalytic subunit alpha,pre-mirnas, precursor mirnas,pri-mirnas, primary mirnas,prr, pattern recognition receptor,rage, receptor for advanced glycation end products,ras, renin-angiotensin system,rbcs, red blood cells,rgmb-as1, rgmb antisense rna 1,rhob, ras homolog gene family member b,rig-i, retinoic acid-inducible gene i,rnai, rna interference,rna pol, rna polymerase,ros, reactive oxygen species,s100a9, s100 calcium-binding protein a9,s protein, spike protein,sars-cov-2, severe acute respiratory syndrome coronavirus 2,sil-6r, soluble il-6r,sirnas, small interfering rnas,socs3, suppressor of cytokine signaling 3,sofa, sequential organ failure assessment score,sry, sex-determining region y,stat, signal transducer and activator of transcription,tab, transforming growth factor β-activated kinase-1 (tak1)-binding protein,tbk1, tank-binding kinase 1,th cells, t helper cells,timp-i, tissue inhibitors of matrix metalloproteinases-i,tlrs, toll-like receptors,tmprss2, transmembrane serine protease 2,tnf-α, tumor necrosis factor alpha,tnfr, tnf receptor,trim27, tripartite motif-containing protein 27,txs, thromboxanes,v-mirna, viral mirna,xpo5, exportin-5
sars-cov-2, covid-19, mirnas, gene regulators, cytokine storm, mirnas-based therapy, 2019-ncov, 2019 novel coronavirus, 3'-utr, 3'-untranslated region, aa, arachidonic acid, ace, angiotensin-converting enzyme, adam17, a disintegrin and metalloproteinase 17, ages, advanced glycation end products, ago, argonaute, ali, acute lung injury, amp, amplifier, ang, angiotensin, anril, antisense noncoding rna in the ink4 locus, ap-1, activator protein 1, apj, apelin receptor, ards, acute respiratory distress syndrome, asos, antisense oligonucleotides, at1r, ang ii receptor type 1, bbb, blood-brain barrier, catb/l, cathepsin b/l, ccl, c-c motif chemokine ligand, cd, cluster of differentiation, cernas, competing endogenous rnas, chd, coronary heart disease, circrnas, circular rnas, cns, central nervous system, covid-19, coronavirus disease 2019, cox, cyclooxygenase, cpla2, cytoplasmic phospholipase a2, crispr, cas13 family of clustered regularly interspaced short palindromic repeats, csf, colony-stimulating factor, cxcl, c-x-c motif chemokine ligand, cyld, cylindromatosis, damps, damage-associated molecular patterns, dcs, dendritic cells, dic, disseminated intravascular coagulation, dmd, dense matted deposits, dmvs, double membrane vesicles, e protein, envelope protein, eae, experimental autoimmune encephalomyelitis, er, endoplasmic reticulum, erk, extracellular signal-regulated kinase, foxo3, forkhead box o3, g-csf, granulocyte csf, gm-csf, granulocyte-macrophage csf, gp130, glycoprotein 130, h3, histone 3, hmgb1, high mobility group box protein 1, hsa, homo sapiens, hsp, heat shock protein, icu, intensive care unit, ifn, interferon, ifns-i, type i ifns, ig, immunoglobulin, iκb-ζ, inhibitor of nuclear factor kappa b zeta, il, interleukin, irf, ifn regulatory factor, isgs, ifn-stimulated genes, jak, janus kinase, k, lysine, kcnq1ot1, kcnq1 overlapping transcript 1, lncrnas, long non-coding rnas, loxs, lipoxygenases, lpls, lysophospholipids, lps, lipopolysaccharide, lts, leukotrienes, m protein, membrane protein, mapk, mitogen-activated protein kinase, mcs, mast cells, m-csf, macrophage csf, mda5, melanoma differentiation-associated protein 5, me2, dimethylation, me3, trimethylation, meg3, maternally expressed gene 3, mers-cov, middle east respiratory syndrome coronavirus, mil-6r, membrane il-6 receptor, mirisc, microrna-induced silencing complex, mirnas, micrornas, mmp, matrix metalloproteinase, mods, multiple organ dysfunction syndrome, mpges-1, microsomal prostaglandin e synthase-1, mrna, messenger rna, myd88, myeloid differentiation factor 88, n protein, nucleocapsid protein, nf-κb, nuclear factor kappa-light-chain-enhancer of activated b cells, nlrp3, nod-, lrr- and pyrin domain-containing protein 3, noxs, nicotinamide adenine dinucleotide phosphate (nadph) oxidases, nsp, non-structural protein, orf, open reading frame, oxpls, oxidized phospholipids, pao2/fio2, pressure of arterial oxygen to fractional inspired oxygen concentration, pbmcs, peripheral blood mononuclear cells, pg, prostaglandin, pkcα, protein kinase c alpha, ppp2ca, protein phosphatase 2 catalytic subunit alpha, pre-mirnas, precursor mirnas, pri-mirnas, primary mirnas, prr, pattern recognition receptor, rage, receptor for advanced glycation end products, ras, renin-angiotensin system, rbcs, red blood cells, rgmb-as1, rgmb antisense rna 1, rhob, ras homolog gene family member b, rig-i, retinoic acid-inducible gene i, rnai, rna interference, rna pol, rna polymerase, ros, reactive oxygen species, s100a9, s100 calcium-binding protein a9, s protein, spike protein, sars-cov-2, severe acute respiratory syndrome coronavirus 2, sil-6r, soluble il-6r, sirnas, small interfering rnas, socs3, suppressor of cytokine signaling 3, sofa, sequential organ failure assessment score, sry, sex-determining region y, stat, signal transducer and activator of transcription, tab, transforming growth factor β-activated kinase-1 (tak1)-binding protein, tbk1, tank-binding kinase 1, th cells, t helper cells, timp-i, tissue inhibitors of matrix metalloproteinases-i, tlrs, toll-like receptors, tmprss2, transmembrane serine protease 2, tnf-α, tumor necrosis factor alpha, tnfr, tnf receptor, trim27, tripartite motif-containing protein 27, txs, thromboxanes, v-mirna, viral mirna, xpo5, exportin-5