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Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization

Received: 11 November 2021    Accepted: 2 December 2021    Published: 24 December 2021
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Abstract

Introduction: The COVID-19 pandemic presented an unprecedented challenge to identify effective drugs and means for their prevention and management. It is more difficult in severe cases due to complications in various vital organs such as the kidneys. Methods: An analytical study was carried out within the framework of the clinical trial “SENTAD-COVID Study” (ClinicalTrial.org, NCT04473170), whose objective was to describe acute kidney injury (AKI) in severe patients with COVID-19 and its relationship with clinical outcomes. A novel stem cells treatment for COVID-19 patients using an autologous peripheral blood nonhematopoietic-enriched stem cells cocktail was developed by the research team of the Abu Dhabi Stem Cells Center and applied at four Abu Dhabi Health Service Company hospitals. The sample consisted of the severe COVID-19 recruited patients: 20 in the experimental arm (Group A) and 24 controls (Group B). Both groups received COVID-19 standard treatment. Results: 29.5% of the patients studied suffered AKI. Mortality was lower in group A compared to the control group (20% vs. 30%, respectively), group A showed 25% AKI while group B 35%, sepsis was significantly lower in the treated group A compared to controls (25% vs. 35%; p=0.0095) Hazard Ratio=0.38, (95% CI: 0.16–0.86), given a Number Needed to Treat=2.5 patients. Group A had a significant reduction in inflammation markers at 25 days compared to the day of recruitment: C-Reactive Protein (median: 207.05 mg/L vs. 27.30 mg/L), IL-6 (median: 355.80 pg/L vs. 35.87 pg/L), and group A was the only one that presented a better proportion of patient with the recovery to normal values of the Neutrophil/Lymphocyte Ratio at 25 days, from 100% to 71.42% p=0.0108. Conclusions: One-third of the patients studied suffered AKI, group A patients showed a clear tendency to improve compared to controls, suggesting that the proposed therapy promotes healing and early recovery in severe COVID-19, which might be related to the anti-inflammatory effect of cellular therapy.

Published in Clinical Medicine Research (Volume 10, Issue 6)
DOI 10.11648/j.cmr.20211006.19
Page(s) 231-237
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

COVID-19, SARS-CoV-2, Acute Kidney Injury, Hemodialysis, Sepsis, Stem Cell Therapies

References
[1] World Health Organization. Novel Coronavirus (COVID-19) Situation. WHO. (June 11th). (2020). Available from: http://covid19.who.int/ (accessed July 27th, 2021).
[2] UAE Ministry of Health and Prevention (MOHAP). National Guidelines for Clinical Management and Treatment of COVID-19 June 1st, 2020. (2020). Available from: https://www.dha.gov.ae/en/HealthRegulation/Documents/National_Guidelines_of_COVID_19_1st_June_2020.pdf (accessed Apr. 2020).
[3] Survey: Physician Practice Patterns Changing As A Result Of COVID-19 [Internet]. (2020). Available from: https://www.prnewswire.com/news-releases/survey-physician-practice-patterns-changing-as-a-result-of-covid-19-301045007.html (Accessed November 16th, 2020).
[4] Study Evaluating the Safety and Efficacy of Autologous Non-Hematopoietic Peripheral Blood Stem Cells in COVID-19 - Full-Text View - ClinicalTrials.gov [Internet]. (2020). Available from: https://clinicaltrials.gov/ct2/show/study/NCT04473170?term=stem+cell&cond=covid&cntry=AE&draw=2&rank=1 (Assessed October 18th, 2020).
[5] Ventura-Carmenate, Y., Alkaabi, F. M., Castillo-Aleman, Y. M, Villegas-Valverde, C. A., Ahmed, Y. M., Almarzooqi, A. A., Torres-Zambrano, G. M., Wade-Mateo, M., Quesada-Saliba, D., Hadi, L. A., Bencomo-Hernandez, A. A., & Rivero-Jimenez, R. A. (2021). Safety and Efficacy of Autologous Non-Hematopoietic Enriched Stem Cell Nebulization in COVID-19 Patients: A Randomized Clinical Trial, Abu Dhabi 2020. Transl Med Commun. (In Press).
[6] Zou X, Chen K, Zou J, Han P, Hao J, Han Z. (2020). Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 14 (2): 185–92.
[7] Puliatti S, Eissa A, Eissa R, Amato M, Mazzone E, Dell'Oglio P, Sighinolfi MC, Zoeir A, Micali S, Bianchi G, Patel V, Wiklund P, Coelho RF, Bernhard JC, Dasgupta P, Mottrie A, Rocco B. (2020). COVID-19 and urology: a comprehensive review of the literature. BJU Int. 125 (6): E7-E14.
[8] Lin L, Lu L, Cao W, Li T. (2020). Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 9 (1): 727–32.
[9] Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. (2020). The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int [Internet]. 97 (5): 824–8. Available from: https://doi.org/10.1016/j.kint.2020.03.001. (Assessed October 18th, 2020).
[10] Majolo F, da Silva GL, Vieira L, Timmers LFSM, Laufer S, Goettert MI. (2021). Review of Trials Currently Testing Stem Cells for Treatment of Respiratory Diseases: Facts Known to Date and Possible Applications to COVID-19. Stem Cell Rev Rep. 17 (1): 44-55.
[11] Ljungberg B, Albiges L, Abu-Ghanem Y, Bensalah K, Dabestani S, Fernández-Pello S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Kuusk T, Lam TB, Marconi L, Merseburger AS, Powles T, Staehler M, Tahbaz R, Volpe A, Bex A. (2019). European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur Urol. 75 (5): 799-810.
[12] Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, Hernández V, Linares Espinós E, Lorch A, Neuzillet Y, Rouanne M, Thalmann GN, Veskimäe E, Ribal MJ, van der Heijden AG. (2021). European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol. 79 (1): 82-104.
[13] Akilli NB, Yortanlı M, Mutlu H, Günaydın YK, Koylu R, Akca HS, Akinci E, Dundar ZD, Cander B. (2014). Prognostic importance of neutrophil-lymphocyte ratio in critically ill patients: short- and long-term outcomes. Am J Emerg Med. 32 (12): 1476-80.
[14] Basbus L, Lapidus MI, Martingano I, Puga MC, Pollán J. (2020). Neutrophil to lymphocyte ratio as a prognostic marker in COVID-19. Medicina. 80 Suppl 3: 31-36.
[15] Fan BE, Chong VCL, Chan SSW, Lim GH, Lim KGE, Tan GB, Mucheli SS, Kuperan P, Ong KH. (2020). Hematologic parameters in patients with COVID-19 infection. Am J Hematol. 95 (6): E131-E134. Erratum in: Am J Hematol. 95 (11): 1442.
[16] Frater JL, Zini G, d'Onofrio G, Rogers HJ. (2020). COVID-19 and the clinical hematology laboratory. Int J Lab Hematol. 42 Suppl 1: 11-18.
[17] Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. (2020). Clin Chem Lab Med. 58 (7): 1131-1134.
[18] World Health Organization. (2020) WHO R&D Blueprint Novel Coronavirus COVID-19 Therapeutic Trial Synopsis. February 18th, 2020. Available at: https://www.who.int/blueprint/priority-diseases/key-action/COVID-19 Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf (Accessed 2021 May 17th).
[19] World Medical Association. (2013). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 310 (20): 2191-4.
[20] Ventura-Carmenate, Y, Bencomo-Hernandez, AA, Alkaabi F, (Inventors). Abu Dhabi Stem Cells Center (Assignee). (2020). Simplified Method For Harvesting Nonhematopoietic Enriched Stem Cells Cocktail (PB-NHESC-C) From Adult Peripheral Blood. In United Emirates Patent No. 3263. UAE Patent. Ministry of Economy.
[21] US Department of Health and Human Services. (2013). Managing Overweight and Obesity in Adults: Systematic Evidence Review from the Obesity Expert Panel. Natl Hear Lung, Blood Inst [Internet]. 501. Available from: https://www.nhlbi.nih.gov/sites/default/files/media/docs/obesity-evidence-review.pdf (Accessed 2021, May 17th).
[22] MedCalc Statistical Software version 20. MedCalc Software Ltd, O. B. (Accessed 2021, May 17th). https://www.medcalc.org.
[23] GraphPad Software. Analise Categorical Data. (Accessed 2021, May 17th). https://www.graphpad.com/quickcalcs/catMenu.
[24] Peckham H, de Gruijter NM, Raine Ch, Radziszewska A, Ciurtin C, Wedderburn LR, Rosser EC, Webb K, Deakin CT. (2020). Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. NATURE COMMUNICATIONS. 11: 6317. https://doi.org/10.1038/s41467-020-19741-6.
[25] Martinez-Rojas MA, Vega-Vega O, Bobadilla NA. Is the kidney a target of SARS-CoV-2? Am J Physiol Renal Physiol. 318 (6): F1454-F1462.
[26] Matthay MA, Aldrich JM, Gotts JE. (2020). Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med. 8 (5): 433-434.
[27] Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. (2020). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 8 (5): 475-481. Erratum in: Lancet Respir Med. 8 (4): e26.
[28] Jeon CY, Neidell M, Jia H, Sinisi M, Larson E. (2012). On the role of length of stay in healthcare-associated bloodstream infection. Infect Control Hosp Epidemiol. 33 (12): 1213-8.
[29] Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA. (2010). Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 28 (12): 2229-38.
[30] Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ. (2010). Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 182 (8): 1047-57.
[31] Tanaka T, Narazaki M, Kishimoto T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 6 (10): a016295.
[32] Chen LYC, Hoiland RL, Stukas S, Wellington CL, Sekhon MS. (2020). Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome. Eur Respir J. 1; 56 (4): 2003006.
[33] Rivero-Jimenez RA, Villegas-Valverde CA, Torres-Zambrano GM, Abdelrazik A, Hader MT, Castillo-Aleman, YM, Ventura-Carmenate Y, Hadi-Abdel L, Bencomo-Hernandez AA. (2021). Severity-related Changes in Laboratory Results During Early Follow-up in COVID-19 Patients Treated with a Novel Cocktail of Stem Cells. Clinical Medicine Research. 10 (4): 133-141.
[34] Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S. (2004). Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 203 (2): 622-30.
[35] Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. (2012). Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 76 (1): 16-32.
Cite This Article
  • APA Style

    Gina Marcela Torres-Zambrano, Carlos Agustin Villegas-Valverde, Antonio Alfonso Bencomo-Hernandez, Loubna Abdel Hadi, Dhanya Adukkadukkam, et al. (2021). Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization. Clinical Medicine Research, 10(6), 231-237. https://doi.org/10.11648/j.cmr.20211006.19

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    ACS Style

    Gina Marcela Torres-Zambrano; Carlos Agustin Villegas-Valverde; Antonio Alfonso Bencomo-Hernandez; Loubna Abdel Hadi; Dhanya Adukkadukkam, et al. Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization. Clin. Med. Res. 2021, 10(6), 231-237. doi: 10.11648/j.cmr.20211006.19

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    AMA Style

    Gina Marcela Torres-Zambrano, Carlos Agustin Villegas-Valverde, Antonio Alfonso Bencomo-Hernandez, Loubna Abdel Hadi, Dhanya Adukkadukkam, et al. Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization. Clin Med Res. 2021;10(6):231-237. doi: 10.11648/j.cmr.20211006.19

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  • @article{10.11648/j.cmr.20211006.19,
      author = {Gina Marcela Torres-Zambrano and Carlos Agustin Villegas-Valverde and Antonio Alfonso Bencomo-Hernandez and Loubna Abdel Hadi and Dhanya Adukkadukkam and Rene Antonio Rivero-Jimenez and Yasmine Maher Ahmed and Yandy Marx Castillo-Aleman and Yendry Ventura-Carmenate},
      title = {Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization},
      journal = {Clinical Medicine Research},
      volume = {10},
      number = {6},
      pages = {231-237},
      doi = {10.11648/j.cmr.20211006.19},
      url = {https://doi.org/10.11648/j.cmr.20211006.19},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cmr.20211006.19},
      abstract = {Introduction: The COVID-19 pandemic presented an unprecedented challenge to identify effective drugs and means for their prevention and management. It is more difficult in severe cases due to complications in various vital organs such as the kidneys. Methods: An analytical study was carried out within the framework of the clinical trial “SENTAD-COVID Study” (ClinicalTrial.org, NCT04473170), whose objective was to describe acute kidney injury (AKI) in severe patients with COVID-19 and its relationship with clinical outcomes. A novel stem cells treatment for COVID-19 patients using an autologous peripheral blood nonhematopoietic-enriched stem cells cocktail was developed by the research team of the Abu Dhabi Stem Cells Center and applied at four Abu Dhabi Health Service Company hospitals. The sample consisted of the severe COVID-19 recruited patients: 20 in the experimental arm (Group A) and 24 controls (Group B). Both groups received COVID-19 standard treatment. Results: 29.5% of the patients studied suffered AKI. Mortality was lower in group A compared to the control group (20% vs. 30%, respectively), group A showed 25% AKI while group B 35%, sepsis was significantly lower in the treated group A compared to controls (25% vs. 35%; p=0.0095) Hazard Ratio=0.38, (95% CI: 0.16–0.86), given a Number Needed to Treat=2.5 patients. Group A had a significant reduction in inflammation markers at 25 days compared to the day of recruitment: C-Reactive Protein (median: 207.05 mg/L vs. 27.30 mg/L), IL-6 (median: 355.80 pg/L vs. 35.87 pg/L), and group A was the only one that presented a better proportion of patient with the recovery to normal values of the Neutrophil/Lymphocyte Ratio at 25 days, from 100% to 71.42% p=0.0108. Conclusions: One-third of the patients studied suffered AKI, group A patients showed a clear tendency to improve compared to controls, suggesting that the proposed therapy promotes healing and early recovery in severe COVID-19, which might be related to the anti-inflammatory effect of cellular therapy.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization
    AU  - Gina Marcela Torres-Zambrano
    AU  - Carlos Agustin Villegas-Valverde
    AU  - Antonio Alfonso Bencomo-Hernandez
    AU  - Loubna Abdel Hadi
    AU  - Dhanya Adukkadukkam
    AU  - Rene Antonio Rivero-Jimenez
    AU  - Yasmine Maher Ahmed
    AU  - Yandy Marx Castillo-Aleman
    AU  - Yendry Ventura-Carmenate
    Y1  - 2021/12/24
    PY  - 2021
    N1  - https://doi.org/10.11648/j.cmr.20211006.19
    DO  - 10.11648/j.cmr.20211006.19
    T2  - Clinical Medicine Research
    JF  - Clinical Medicine Research
    JO  - Clinical Medicine Research
    SP  - 231
    EP  - 237
    PB  - Science Publishing Group
    SN  - 2326-9057
    UR  - https://doi.org/10.11648/j.cmr.20211006.19
    AB  - Introduction: The COVID-19 pandemic presented an unprecedented challenge to identify effective drugs and means for their prevention and management. It is more difficult in severe cases due to complications in various vital organs such as the kidneys. Methods: An analytical study was carried out within the framework of the clinical trial “SENTAD-COVID Study” (ClinicalTrial.org, NCT04473170), whose objective was to describe acute kidney injury (AKI) in severe patients with COVID-19 and its relationship with clinical outcomes. A novel stem cells treatment for COVID-19 patients using an autologous peripheral blood nonhematopoietic-enriched stem cells cocktail was developed by the research team of the Abu Dhabi Stem Cells Center and applied at four Abu Dhabi Health Service Company hospitals. The sample consisted of the severe COVID-19 recruited patients: 20 in the experimental arm (Group A) and 24 controls (Group B). Both groups received COVID-19 standard treatment. Results: 29.5% of the patients studied suffered AKI. Mortality was lower in group A compared to the control group (20% vs. 30%, respectively), group A showed 25% AKI while group B 35%, sepsis was significantly lower in the treated group A compared to controls (25% vs. 35%; p=0.0095) Hazard Ratio=0.38, (95% CI: 0.16–0.86), given a Number Needed to Treat=2.5 patients. Group A had a significant reduction in inflammation markers at 25 days compared to the day of recruitment: C-Reactive Protein (median: 207.05 mg/L vs. 27.30 mg/L), IL-6 (median: 355.80 pg/L vs. 35.87 pg/L), and group A was the only one that presented a better proportion of patient with the recovery to normal values of the Neutrophil/Lymphocyte Ratio at 25 days, from 100% to 71.42% p=0.0108. Conclusions: One-third of the patients studied suffered AKI, group A patients showed a clear tendency to improve compared to controls, suggesting that the proposed therapy promotes healing and early recovery in severe COVID-19, which might be related to the anti-inflammatory effect of cellular therapy.
    VL  - 10
    IS  - 6
    ER  - 

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Author Information
  • Clinical Department, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Stem Cells Processing Laboratory, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Immunology Department, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

  • Clinical Department, Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates

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