Abstract
It has been almost 18 months since the first outbreak of COVID-19 disease was reported in Wuhan, China. This unexpected devastating phenomenon, raised a great deal of concerns and anxiety among people around the world and imposed a huge economic burden on the nations’ health care systems. Accordingly, clinical scientists, pharmacologists and physicians worldwide felt an urgent demand for a safe, effective therapeutic agent, treatment strategy or vaccine in order to prevent or cure the recently-emerged disease. Initially, due to the lack of specific pharmacological agents and approved vaccines to combat the COVID-19, the disease control in the confirmed cases was limited to supportive care. Accordingly, repositioning or repurposing current drugs and examining their possible therapeutic efficacy received a great deal of attention. Despite revealing promising results in some clinical trials, the overall results are conflicting. For this reason, there is an urgent need to seek and investigate other potential therapeutics. Mesenchymal stem cells (MSC), representing immunomodulatory and regenerative capacity to treat both curable and intractable diseases, have been investigated in COVID-19 clinical trials carried out in different parts of the world. Nevertheless, up to now, none of the MSC-based approaches has been approved in controlling COVID-19 infection. Thanks to the fact that the final solution for defeating the pandemic is developing a safe, effective vaccine, enormous efforts and clinical research have been carried out.
In this review, we will concisely discuss the safety and efficacy of the most relevant pharmacological agents, MSC-based approaches and candidate vaccines for treating and preventing COVID-19 infection.
Keywords: Mesenchymal stem cell, cell therapy, drug, drug repositioning, vaccine, COVID-19, SARS-CoV-2.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jclinepi.2020.06.008] [PMID: 32540385]
[http://dx.doi.org/10.1097/JCMA.0000000000000270] [PMID: 32134861]
[http://dx.doi.org/10.1016/j.bj.2020.04.007] [PMID: 32387617]
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[http://dx.doi.org/10.1002/jmv.25750] [PMID: 32141624]
[http://dx.doi.org/10.1002/jmv.25807] [PMID: 32232980]
[http://dx.doi.org/10.1016/j.isci.2020.101303] [PMID: 32622261]
[http://dx.doi.org/10.1016/j.phrs.2020.104859] [PMID: 32360480]
[http://dx.doi.org/10.1016/j.fct.2020.111639] [PMID: 32707160]
[http://dx.doi.org/10.1016/j.ejphar.2020.173643] [PMID: 33065092]
[http://dx.doi.org/10.3390/biom11040607] [PMID: 33921886]
[PMID: 32839921]
[http://dx.doi.org/10.1002/cbin.11440] [PMID: 32767687]
[http://dx.doi.org/10.1007/s12015-020-10037-2] [PMID: 32920752]
[http://dx.doi.org/10.1016/j.lfs.2020.118588] [PMID: 33049279]
[PMID: 32950067]
[http://dx.doi.org/10.1007/s11010-020-03924-2] [PMID: 33029696]
[http://dx.doi.org/10.14740/jocmr4490] [PMID: 34007358]
[http://dx.doi.org/10.1080/14760584.2021.1875824] [PMID: 33435774]
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[http://dx.doi.org/10.1007/s40121-020-00295-5] [PMID: 32292686]
[http://dx.doi.org/10.1002/jmv.25681] [PMID: 31967327]
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[http://dx.doi.org/10.3390/v13020202] [PMID: 33572857]
[http://dx.doi.org/10.2147/CPAA.S284809] [PMID: 33363416]
[http://dx.doi.org/10.1016/j.cca.2020.05.044] [PMID: 32474009]
[http://dx.doi.org/10.1007/s12015-020-09973-w] [PMID: 32281052]
[http://dx.doi.org/10.15585/mmwr.mm6928a2] [PMID: 32673296]
[http://dx.doi.org/10.4103/ijo.IJO_639_20] [PMID: 32317431]
[http://dx.doi.org/10.1007/s00228-020-02963-4] [PMID: 32696234]
[http://dx.doi.org/10.7573/dic.2020-4-6] [PMID: 32499832]
[http://dx.doi.org/10.1111/joim.13144] [PMID: 32696489]
[http://dx.doi.org/10.3389/fimmu.2020.01708] [PMID: 32754163]
[http://dx.doi.org/10.1016/j.lfs.2020.118054] [PMID: 32663575]
[http://dx.doi.org/10.1007/s40121-021-00399-6] [PMID: 33495967]
[http://dx.doi.org/10.5694/mja2.50698] [PMID: 32677734]
[http://dx.doi.org/10.1021/acscentsci.0c00272]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.305227] [PMID: 26941423]
[http://dx.doi.org/10.1002/jcb.26169] [PMID: 28543595]
[http://dx.doi.org/10.1007/s12015-020-10110-w] [PMID: 33511518]
[http://dx.doi.org/10.1038/s41409-019-0616-z] [PMID: 31431712]
[http://dx.doi.org/10.1155/2018/6726185]
[http://dx.doi.org/10.1155/2016/5646384] [PMID: 26770208]
[http://dx.doi.org/10.1177/0963689719837897] [PMID: 31018669]
[http://dx.doi.org/10.1016/j.pharmthera.2015.02.003] [PMID: 25709098]
[http://dx.doi.org/10.3389/fimmu.2020.01563] [PMID: 32719683]
[http://dx.doi.org/10.1002/jgh3.12141] [PMID: 31276044]
[http://dx.doi.org/10.3389/fbioe.2020.00148] [PMID: 32185170]
[http://dx.doi.org/10.2174/1574888X14666190823144928] [PMID: 31441734]
[PMID: 33150562]
[http://dx.doi.org/10.1089/wound.2015.0627] [PMID: 27076993]
[http://dx.doi.org/10.3389/fimmu.2020.01446] [PMID: 32612617]
[http://dx.doi.org/10.1097/AIA.0000000000000177] [PMID: 29227309]
[http://dx.doi.org/10.3389/fmolb.2020.624093] [PMID: 33537342]
[http://dx.doi.org/10.1186/s12967-021-02862-x] [PMID: 33971907]
[http://dx.doi.org/10.1038/s41572-019-0069-0] [PMID: 30872586]
[http://dx.doi.org/10.1007/s00134-020-05942-6] [PMID: 32016537]
[http://dx.doi.org/10.1016/j.jocit.2014.12.001]
[http://dx.doi.org/10.1152/physrev.00019.2015] [PMID: 27335447]
[http://dx.doi.org/10.5966/sctm.2015-0021] [PMID: 26285659]
[http://dx.doi.org/10.1002/stem.2779] [PMID: 29341339]
[http://dx.doi.org/10.14336/AD.2020.0228] [PMID: 32257537]
[http://dx.doi.org/10.1089/scd.2008.0253] [PMID: 19099374]
[http://dx.doi.org/10.1002/sctm.20-0146] [PMID: 32472653]
[http://dx.doi.org/10.1038/s41392-020-00286-5] [PMID: 32855385]
[http://dx.doi.org/10.1186/s13287-021-02165-4] [PMID: 33514427]
[http://dx.doi.org/10.1186/s13287-020-01875-5] [PMID: 32811531]
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 33731711]
[http://dx.doi.org/10.1186/s13287-020-02006-w] [PMID: 33397467]
[http://dx.doi.org/10.1186/s13287-020-01804-6] [PMID: 32698898]
[http://dx.doi.org/10.1038/s41584-020-0372-x] [PMID: 32034323]
[http://dx.doi.org/10.1007/s40261-018-0656-y] [PMID: 29737455]
[PMID: 31768005]
[http://dx.doi.org/10.4049/jimmunol.1000702] [PMID: 21398612]
[http://dx.doi.org/10.1146/annurev-med-043015-123453] [PMID: 27813878]
[http://dx.doi.org/10.1016/j.molcel.2013.05.022] [PMID: 23747010]
[http://dx.doi.org/10.3899/jrheum.161063] [PMID: 28250164]
[http://dx.doi.org/10.1136/postgradmedj-2017-135236] [PMID: 29353247]
[http://dx.doi.org/10.3899/jrheum.161351] [PMID: 28507183]
[http://dx.doi.org/10.1016/j.cmi.2020.05.006] [PMID: 32422406]
[http://dx.doi.org/10.1016/j.drudis.2020.04.021] [PMID: 32371138]
[http://dx.doi.org/10.1016/j.dsx.2020.03.011] [PMID: 32247211]
[http://dx.doi.org/10.1074/jbc.M116.716100] [PMID: 26953343]
[http://dx.doi.org/10.1371/journal.ppat.1009212] [PMID: 33465165]
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID: 32074550]
[http://dx.doi.org/10.1101/2020.03.22.20040758]
[http://dx.doi.org/10.1056/NEJMoa2012410] [PMID: 32379955]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[http://dx.doi.org/10.1016/j.micpath.2020.104228] [PMID: 32344177]
[http://dx.doi.org/10.1016/j.tmaid.2020.101663] [PMID: 32289548]
[http://dx.doi.org/10.1016/j.medmal.2020.03.006] [PMID: 32240719]
[http://dx.doi.org/10.1016/j.retram.2020.04.002] [PMID: 32340837]
[http://dx.doi.org/10.1016/j.acvd.2020.04.001] [PMID: 32331979]
[http://dx.doi.org/10.1074/jbc.AC120.013056] [PMID: 32094225]
[http://dx.doi.org/10.1016/j.tmaid.2020.101647] [PMID: 32247927]
[http://dx.doi.org/10.1007/s15010-020-01557-7] [PMID: 33389708]
[http://dx.doi.org/10.1056/NEJMoa2001191] [PMID: 32004427]
[http://dx.doi.org/10.1056/NEJMoa2007016] [PMID: 32275812]
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9] [PMID: 32423584]
[http://dx.doi.org/10.29121/granthaalayah.v8.i4.2020.2]
[PMID: 33619447]
[http://dx.doi.org/10.1016/j.antiviral.2018.03.003] [PMID: 29524445]
[http://dx.doi.org/10.1016/j.eng.2020.03.007] [PMID: 32346491]
[http://dx.doi.org/10.1101/2020.03.17.20037432]
[http://dx.doi.org/10.1016/j.cmi.2020.04.026] [PMID: 32344167]
[http://dx.doi.org/10.1016/j.jgg.2020.02.001] [PMID: 32173287]
[PMID: 19209283]
[http://dx.doi.org/10.1002/prp2.705] [PMID: 33421347]
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[http://dx.doi.org/10.3346/jkms.2020.35.e89] [PMID: 32080993]
[http://dx.doi.org/10.1016/j.ejmech.2020.112862] [PMID: 33070079]
[http://dx.doi.org/10.1016/j.virol.2015.03.032] [PMID: 25864107]
[http://dx.doi.org/10.1016/j.autrev.2018.04.006] [PMID: 30103044]
[http://dx.doi.org/10.1111/cei.13517] [PMID: 32935331]
[http://dx.doi.org/10.1371/journal.pntd.0004572] [PMID: 27537413]
[http://dx.doi.org/10.1038/nrmicro3143] [PMID: 24217413]
[http://dx.doi.org/10.2174/157489106778777673] [PMID: 18221154]
[http://dx.doi.org/10.1007/978-3-662-45024-6_2]
[http://dx.doi.org/10.1016/j.vacun.2020.05.002]
[http://dx.doi.org/10.3934/publichealth.2021011] [PMID: 33575413]
[http://dx.doi.org/10.3390/v11010074] [PMID: 30658390]
[http://dx.doi.org/10.1038/nbt1105-1359] [PMID: 16273061]
[http://dx.doi.org/10.1080/21645515.2016.1210729] [PMID: 27455345]
[http://dx.doi.org/10.3390/vaccines8040680] [PMID: 33202961]
[http://dx.doi.org/10.3389/fmicb.2019.01781] [PMID: 31428074]
[http://dx.doi.org/10.1016/S0140-6736(20)31604-4] [PMID: 32702298]
[http://dx.doi.org/10.1016/S0140-6736(20)32661-1] [PMID: 33306989]
[http://dx.doi.org/10.3390/ijms19113605] [PMID: 30445702]
[http://dx.doi.org/10.1111/j.1600-065X.2010.00980.x] [PMID: 21198665]
[http://dx.doi.org/10.2174/1574891X113089990037] [PMID: 23444943]
[http://dx.doi.org/10.1038/s41392-020-00352-y] [PMID: 33051445]
[http://dx.doi.org/10.1016/j.dsx.2020.07.022] [PMID: 32755836]
[http://dx.doi.org/10.1038/s41467-020-16505-0] [PMID: 32433465]
[http://dx.doi.org/10.1016/j.eclinm.2020.100689] [PMID: 33392485]
[http://dx.doi.org/10.1038/nrd.2017.243] [PMID: 29326426]
[http://dx.doi.org/10.3389/fimmu.2020.608460] [PMID: 33414790]
[http://dx.doi.org/10.4161/rna.22269] [PMID: 23064118]
[http://dx.doi.org/10.1016/j.heliyon.2020.e05007] [PMID: 32984620]
[http://dx.doi.org/10.1073/pnas.111145698] [PMID: 11416182]
[http://dx.doi.org/10.1056/NEJMoa2022483]
[http://dx.doi.org/10.3390/cells10020206] [PMID: 33494237]
[http://dx.doi.org/10.1056/NEJMoa2035389] [PMID: 33378609]
[PMID: 32366816]
[http://dx.doi.org/10.1056/NEJMoa2024671] [PMID: 32722908]
[http://dx.doi.org/10.3390/vaccines9010030] [PMID: 33429880]
[http://dx.doi.org/10.1016/j.clim.2020.108634] [PMID: 33217545]
[http://dx.doi.org/10.1056/NEJMoa2034577] [PMID: 33301246]
[http://dx.doi.org/10.1038/s41565-020-0739-9] [PMID: 32807876]
[http://dx.doi.org/10.1002/adbi.201800219] [PMID: 31728404]
[http://dx.doi.org/10.1021/acsnano.0c04006] [PMID: 32571007]
[http://dx.doi.org/10.1186/1471-2172-11-65] [PMID: 21194475]
[http://dx.doi.org/10.1021/mp200553x] [PMID: 22356166]