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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Meta-Analysis

Efficacy and Safety of Mesenchymal Stromal Cells Therapy for COVID-19 Infection: A Systematic Review and Meta-analysis

Author(s): Yaxin Li, Ziyang Wei, Xinyu Ma, Jing Xu, Xia Zhao, Qilong Cao and Guohu Di*

Volume 18, Issue 1, 2023

Published on: 28 December, 2021

Page: [143 - 152] Pages: 10

DOI: 10.2174/1574888X16666211206145839

Price: $65

Abstract

Background: Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease prevalent worldwide with a high mortality rate, and there is currently no specific medicine to treat patients.

Objective: We aimed to assess the safety and efficacy of stem cell therapy for COVID-19 by providing references for subsequent clinical treatments and trials.

Method: We systematically searched PubMed, Embase, Cochrane, and Web of Science, using the following keywords: “stem cell” or “stromal cell” and “COVID-19.” Controlled clinical trials published in English until 24th August 2021 were included. We followed the PRISMA guidelines and used Cochrane Collaboration’s tool for assessing the risk of bias. We analysed the data using a fixed-effect model.

Results: We identified 1779 studies, out of which eight were eligible and included in this study. Eight relevant studies consisted of 156 patients treated with stem cells and 144 controls (300 individuals in total). There were no SAEs associated with stem cell therapy in all six studies, and no significant differences in AEs (p = 0.09, I2 = 40%, OR = 0.53, 95% CI: 0.26 to 1.09) between the experimental group and control group were observed. Moreover, the meta-analysis found that stem cell therapy effectively reduced the high mortality rate of COVID-19 (14/156 vs. 43/144; p<0.0001, I2 = 0%, OR=0.18, 95% CI: 0.08 to 0.41).

Conclusion: This study suggests that MSCs therapy for COVID-19 has shown some promising results in safety and efficacy. It effectively reduces the high mortality rate of COVID-19 and does not increase the incidence of adverse events.

Keywords: Mesenchymal stromal cells, COVID-19, safety, efficacy, adverse effect, meta-analysis.

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[1]
World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Available from: https://covid19.who.int/
[2]
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol 2021; 93(1): 250-6.
[http://dx.doi.org/10.1002/jmv.26232] [PMID: 32592501]
[3]
Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020; 323(16): 1574-81.
[http://dx.doi.org/10.1001/jama.2020.5394] [PMID: 32250385]
[4]
Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383(27): 2603-15.
[http://dx.doi.org/10.1056/NEJMoa2034577] [PMID: 33301246]
[5]
Zhu FC, Guan XH, Li YH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2020; 396(10249): 479-88.
[http://dx.doi.org/10.1016/S0140-6736(20)31605-6] [PMID: 32702299]
[6]
Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020; 396(10249): 467-78.
[http://dx.doi.org/10.1016/S0140-6736(20)31604-4] [PMID: 32702298]
[7]
Wouters OJ, Shadlen KC, Salcher-Konrad M, et al. Challenges in ensuring global access to COVID-19 vaccines: Production, affordability, allocation, and deployment. Lancet 2021; 397(10278): 1023-34.
[http://dx.doi.org/10.1016/S0140-6736(21)00306-8] [PMID: 33587887]
[8]
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-74.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[9]
Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 Pneumonia. Aging Dis 2020; 11(2): 216-28.
[http://dx.doi.org/10.14336/AD.2020.0228] [PMID: 32257537]
[10]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[11]
Kox M, Waalders NJB, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine levels in critically Ill patients with COVID-19 and other conditions. JAMA 2020; 324: 1565-7.
[http://dx.doi.org/10.1001/jama.2020.17052] [PMID: 32880615]
[12]
McElvaney OJ, McEvoy NL, McElvaney OF, et al. Characterization of the inflammatory response to severe COVID-19 illness. Am J Respir Crit Care Med 2020; 202(6): 812-21.
[http://dx.doi.org/10.1164/rccm.202005-1583OC] [PMID: 32584597]
[13]
Fu L, Wang B, Yuan T, et al. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. J Infect 2020; 80(6): 656-65.
[http://dx.doi.org/10.1016/j.jinf.2020.03.041] [PMID: 32283155]
[14]
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473-4.
[http://dx.doi.org/10.1126/science.abb8925] [PMID: 32303591]
[15]
Gorman E, Millar J, McAuley D, O’Kane C. Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: Optimizing the therapeutic potential. Expert Rev Respir Med 2021; 15(3): 301-24.
[http://dx.doi.org/10.1080/17476348.2021.1848555] [PMID: 33172313]
[16]
Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 2018; 22(6): 824-33.
[http://dx.doi.org/10.1016/j.stem.2018.05.004] [PMID: 29859173]
[17]
Yen BL, Yen ML, Wang LT, Liu KJ, Sytwu HK. Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID-19. Stem Cells Transl Med 2020; 9(10): 1163-73.
[http://dx.doi.org/10.1002/sctm.20-0186] [PMID: 32526079]
[18]
Childs PG, Reid S, Salmeron-Sanchez M, Dalby MJ. Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products. Biochem J 2020; 477(17): 3349-66.
[http://dx.doi.org/10.1042/BCJ20190382] [PMID: 32941644]
[19]
Ball LM, Bernardo ME, Roelofs H, et al. Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease. Br J Haematol 2013; 163(4): 501-9.
[http://dx.doi.org/10.1111/bjh.12545] [PMID: 23992039]
[20]
Matthay MA, Calfee CS, Zhuo H, et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med 2019; 7(2): 154-62.
[http://dx.doi.org/10.1016/S2213-2600(18)30418-1] [PMID: 30455077]
[21]
Dilogo IH, Aditianingsih D, Sugiarto A, et al. Umbilical cord mesenchymal stromal cells as critical COVID-19 adjuvant therapy: A randomized controlled trial. Stem Cells Transl Med 2021; 10(9): 1279-87.
[http://dx.doi.org/10.1002/sctm.21-0046] [PMID: 34102020]
[22]
Häberle H, Magunia H, Lang P, et al. Mesenchymal stem cell therapy for severe COVID-19 ARDS. J Intensive Care Med 2021; 36(6): 681-8.
[http://dx.doi.org/10.1177/0885066621997365] [PMID: 33663244]
[23]
Meng F, Xu R, Wang S, et al. Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: A phase 1 clinical trial. Signal Transduct Target Ther 2020; 5(1): 172.
[http://dx.doi.org/10.1038/s41392-020-00286-5] [PMID: 32855385]
[24]
Xu X, Jiang W, Chen L, et al. Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial. Clin Transl Med 2021; 11(2): e297.
[http://dx.doi.org/10.1002/ctm2.297] [PMID: 33634996]
[25]
Lanzoni G, Linetsky E, Correa D, et al. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial. Stem Cells Transl Med 2021; 10(5): 660-73.
[http://dx.doi.org/10.1002/sctm.20-0472] [PMID: 33400390]
[26]
Shu L, Niu C, Li R, et al. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther 2020; 11(1): 361.
[http://dx.doi.org/10.1186/s13287-020-01875-5] [PMID: 32811531]
[27]
Shi L, Huang H, Lu X, et al. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: A randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther 2021; 6(1): 58.
[http://dx.doi.org/10.1038/s41392-021-00488-5] [PMID: 33568628]
[28]
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A review. JAMA 2020; 323(18): 1824-36.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[29]
Yadav P, Vats R, Bano A, Bhardwaj R. Mesenchymal stem cell immunomodulation and regeneration therapeutics as an ameliorative approach for COVID-19 pandemics. Life Sci 2020; 263: 118588.
[http://dx.doi.org/10.1016/j.lfs.2020.118588] [PMID: 33049279]
[30]
Loy H, Kuok DIT, Hui KPY, et al. Therapeutic implications of human umbilical cord mesenchymal stromal cells in attenuating influenza A(H5N1) Virus-Associated Acute Lung Injury. J Infect Dis 2019; 219(2): 186-96.
[http://dx.doi.org/10.1093/infdis/jiy478] [PMID: 30085072]
[31]
Choudhery MS, Harris DT. Stem cell therapy for COVID-19: Possibilities and challenges. Cell Biol Int 2020; 44(11): 2182-91.
[http://dx.doi.org/10.1002/cbin.11440] [PMID: 32767687]
[32]
Kot M, Baj-Krzyworzeka M, Szatanek R, Musiał-Wysocka A, Suda-Szczurek M, Majka M. The importance of HLA assessment in “Off-the-Shelf” allogeneic mesenchymal stem cells based-therapies. Int J Mol Sci 2019; 20(22): 20.
[http://dx.doi.org/10.3390/ijms20225680] [PMID: 31766164]
[33]
Hasan SS, Capstick T, Ahmed R, et al. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: A systematic review and meta-analysis. Expert Rev Respir Med 2020; 14(11): 1149-63.
[http://dx.doi.org/10.1080/17476348.2020.1804365] [PMID: 32734777]
[34]
Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021; 384(8): 693-704.
[http://dx.doi.org/10.1056/NEJMoa2021436] [PMID: 32678530]
[35]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[36]
Mahase E. Covid-19: Low dose steroid cuts death in ventilated patients by one third, trial finds. BMJ 2020; 369: m2422.
[http://dx.doi.org/10.1136/bmj.m2422] [PMID: 32546467]
[37]
Noreen S, Maqbool I, Madni A. Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur J Pharmacol 2021; 894: 173854.
[http://dx.doi.org/10.1016/j.ejphar.2021.173854] [PMID: 33428898]
[38]
Wu J, Hu Z, Wang L, et al. First case of COVID-19 infused with hESC derived immunity- and matrix-regulatory cells. Cell Prolif 2020; 53(12): e12943.
[http://dx.doi.org/10.1111/cpr.12943] [PMID: 33107123]
[39]
Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021; 384(16): 1503-16.
[http://dx.doi.org/10.1056/NEJMoa2028700] [PMID: 33631066]
[40]
Salvarani C, Dolci G, Massari M, et al. Effect of Tocilizumab vs. standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: A randomized clinical trial. JAMA Intern Med 2021; 181(1): 24-31.
[http://dx.doi.org/10.1001/jamainternmed.2020.6615] [PMID: 33080005]
[41]
Soin AS, Kumar K, Choudhary NS, et al. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): An open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med 2021; 9(5): 511-21.
[http://dx.doi.org/10.1016/S2213-2600(21)00081-3] [PMID: 33676589]
[42]
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of Tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020; 383(24): 2333-44.
[http://dx.doi.org/10.1056/NEJMoa2028836] [PMID: 33085857]
[43]
Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ 2021; 372: n84.
[http://dx.doi.org/10.1136/bmj.n84] [PMID: 33472855]
[44]
Alsharidah S, Ayed M, Ameen RM, et al. COVID-19 convalescent plasma treatment of moderate and severe cases of SARS- CoV-2 infection: A multicenter interventional study. Int J Infect Dis 2021; 103: 439-46.
[45]
Altuntas F, Yigenoglu TN, Bascı S, et al. Convalescent plasma therapy in patients with COVID-19. Transfus Apheresis Sci 2021; 60: 103017.
[46]
Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA 2020; 117(17): 9490-6.
[http://dx.doi.org/10.1073/pnas.2004168117] [PMID: 32253318]
[47]
Simonovich VA, Burgos Pratx LD, Scibona P, et al. A Randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med 2021; 384(7): 619-29.
[http://dx.doi.org/10.1056/NEJMoa2031304] [PMID: 33232588]
[48]
Zhang B, Liu S, Tan T, et al. Treatment with convalescent plasma for critically Ill Patients with severe acute respiratory syndrome Coronavirus 2 infection. Chest 2020; 158(1): e9-e13.
[http://dx.doi.org/10.1016/j.chest.2020.03.039] [PMID: 32243945]
[49]
Sánchez-Guijo F, García-Arranz M, López-Parra M, et al. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study. EClinicalMedicine 2020; 25: 100454.
[http://dx.doi.org/10.1016/j.eclinm.2020.100454] [PMID: 32838232]
[50]
Qu W, Wang Z, Hare JM, et al. Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome. Stem Cells Transl Med 2020; 9(9): 1007-22.
[http://dx.doi.org/10.1002/sctm.20-0146] [PMID: 32472653]
[51]
Lotfi M, Hamblin MR, Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020; 508: 254-66.
[52]
Abreu SC, Lopes-Pacheco M, Weiss DJ, Rocco PRM. Mesenchymal stromal cell-derived extracellular vesicles in lung diseases: Current status and perspectives. Front Cell Dev Biol 2021; 9: 600711.
[http://dx.doi.org/10.3389/fcell.2021.600711] [PMID: 33659247]
[53]
Mateo-Urdiales A, Spila Alegiani S, Fabiani M, et al. Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021. Euro Surveill 2021; 26(25): 2100507.
[54]
Lai CC, Wang CY, Wang YH, Hsueh SC, Ko WC, Hsueh PR. Global epidemiology of coronavirus disease 2019 (COVID-19): Disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status. Int J Antimicrob Agents 2020; 55(4): 105946.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105946] [PMID: 32199877]
[55]
Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet 2020; 395(10229): 1014-5.
[http://dx.doi.org/10.1016/S0140-6736(20)30633-4] [PMID: 32197108]
[56]
Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome Coronavirus infection. J Immunol 2017; 198: 4046-53.
[http://dx.doi.org/10.4049/jimmunol.1601896]
[57]
Jaillon S, Berthenet K, Garlanda C. Sexual dimorphism in innate immunity. Clin Rev Allergy Immunol 2019; 56(3): 308-21.
[http://dx.doi.org/10.1007/s12016-017-8648-x] [PMID: 28963611]
[58]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395(10223): 507-13.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]

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