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USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT

BACKGROUND: Currently, there is no specific treatment for coronavirus disease, and some drugs and cell-based therapy have been tested as alternatives. This work aims to evaluate the effects of the combined use of humanized recombinant monoclonal antibody capable of binding the IL-6 receptor (Tociliz...

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Autores principales: Senegaglia, AC, Rebelatto, CLK, Franck, CL, Lima, JS, Daga, DR, Shigunov, P, Azambuja, AP, Bana, EG, Marsaro, DB, Schaidt, B, Micosky, A, Jamur, VR, Vaz, IM, Schluga, Y, Leite, LMB, Ribeiro, LL, Correa, A, Brofman, PRS
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier Inc. 2021
Materias:
104
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079859/
http://dx.doi.org/10.1016/j.jcyt.2021.02.111
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author Senegaglia, AC
Rebelatto, CLK
Franck, CL
Lima, JS
Daga, DR
Shigunov, P
Azambuja, AP
Bana, EG
Marsaro, DB
Schaidt, B
Micosky, A
Jamur, VR
Vaz, IM
Schluga, Y
Leite, LMB
Ribeiro, LL
Correa, A
Brofman, PRS
author_facet Senegaglia, AC
Rebelatto, CLK
Franck, CL
Lima, JS
Daga, DR
Shigunov, P
Azambuja, AP
Bana, EG
Marsaro, DB
Schaidt, B
Micosky, A
Jamur, VR
Vaz, IM
Schluga, Y
Leite, LMB
Ribeiro, LL
Correa, A
Brofman, PRS
author_sort Senegaglia, AC
collection PubMed
description BACKGROUND: Currently, there is no specific treatment for coronavirus disease, and some drugs and cell-based therapy have been tested as alternatives. This work aims to evaluate the effects of the combined use of humanized recombinant monoclonal antibody capable of binding the IL-6 receptor (Tocilizumab), and umbilical cord tissue-derived mesenchymal stromal cells (UCT-MSC) in the treatment of a patient with severe COVID-19 admitted to the intensive care unit (IUC) and submitted to mechanical ventilation. METHODS: This study is part of a project approved by the National Research Ethics Commission (CONEP); CAAE: 30833820.8.0000.0020. The patient had a diagnostic criterion for the severe acute respiratory syndrome resulting from infection with SARS-CoV-2 and received two 400 mg doses of tocilizumab, three infusions of 500,000 CTM / kg plus full anticoagulation. TCU-MSC were obtained from healthy donors. The following parameters were evaluated in the pre-infusion of cells (D1), on the day following each infusion (D2, D4, and D6), on the 14th and 60th day after the first infusion (D14 and D60): viral load, immune response (Regulatory T lymphocytes), C-reactive protein level in plasma, oxygen saturation, respiratory rate, total lymphocyte count and subpopulations (platelets, inflammatory cells, and reticulocytes), TGO / TGP, increased prothrombin time, D-dimer, creatinine, troponin. RESULTS: The relative viral quantification decreased gradually from 1 (D1) to 0.06 (D6) RdRP / RNApol, undetectable in D14. An increase in the absolute number of total lymphocytes / µL has also been seen to have progressively increased from 281 (D1) to 954.9 (D6) and since then decreased to 641.6 in D60 in the same way as T lymphocytes 148.6 (D1) 642.6 (D6) 607.4 (D14) 485.7 (D60), CD4 T lymphocytes, 102 (D1) 481.2 (D6) 459.5 (D14) 358 (D60) and Treg lymphocytes 10.8 (D1) 34 (D6) 29.8 (D14), 25.9 (D60). Plasmablasts, in contrast, decreased from 52 (D1) to 4.5 (D6) to almost undetectable in D60 (0.2). Laboratory tests outside the reference values decreased during the follow-up from D1 to D14 were within the normal parameters at D60. The patient was extubated uneventfully on D6, discharged from the ICU on D10, and the hospital on D14. CONCLUSION: the combined use of tocilizumab and MSC is safe, without adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.
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spelling pubmed-80798592021-04-28 USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT Senegaglia, AC Rebelatto, CLK Franck, CL Lima, JS Daga, DR Shigunov, P Azambuja, AP Bana, EG Marsaro, DB Schaidt, B Micosky, A Jamur, VR Vaz, IM Schluga, Y Leite, LMB Ribeiro, LL Correa, A Brofman, PRS Cytotherapy 104 BACKGROUND: Currently, there is no specific treatment for coronavirus disease, and some drugs and cell-based therapy have been tested as alternatives. This work aims to evaluate the effects of the combined use of humanized recombinant monoclonal antibody capable of binding the IL-6 receptor (Tocilizumab), and umbilical cord tissue-derived mesenchymal stromal cells (UCT-MSC) in the treatment of a patient with severe COVID-19 admitted to the intensive care unit (IUC) and submitted to mechanical ventilation. METHODS: This study is part of a project approved by the National Research Ethics Commission (CONEP); CAAE: 30833820.8.0000.0020. The patient had a diagnostic criterion for the severe acute respiratory syndrome resulting from infection with SARS-CoV-2 and received two 400 mg doses of tocilizumab, three infusions of 500,000 CTM / kg plus full anticoagulation. TCU-MSC were obtained from healthy donors. The following parameters were evaluated in the pre-infusion of cells (D1), on the day following each infusion (D2, D4, and D6), on the 14th and 60th day after the first infusion (D14 and D60): viral load, immune response (Regulatory T lymphocytes), C-reactive protein level in plasma, oxygen saturation, respiratory rate, total lymphocyte count and subpopulations (platelets, inflammatory cells, and reticulocytes), TGO / TGP, increased prothrombin time, D-dimer, creatinine, troponin. RESULTS: The relative viral quantification decreased gradually from 1 (D1) to 0.06 (D6) RdRP / RNApol, undetectable in D14. An increase in the absolute number of total lymphocytes / µL has also been seen to have progressively increased from 281 (D1) to 954.9 (D6) and since then decreased to 641.6 in D60 in the same way as T lymphocytes 148.6 (D1) 642.6 (D6) 607.4 (D14) 485.7 (D60), CD4 T lymphocytes, 102 (D1) 481.2 (D6) 459.5 (D14) 358 (D60) and Treg lymphocytes 10.8 (D1) 34 (D6) 29.8 (D14), 25.9 (D60). Plasmablasts, in contrast, decreased from 52 (D1) to 4.5 (D6) to almost undetectable in D60 (0.2). Laboratory tests outside the reference values decreased during the follow-up from D1 to D14 were within the normal parameters at D60. The patient was extubated uneventfully on D6, discharged from the ICU on D10, and the hospital on D14. CONCLUSION: the combined use of tocilizumab and MSC is safe, without adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2. Published by Elsevier Inc. 2021-04 2021-04-28 /pmc/articles/PMC8079859/ http://dx.doi.org/10.1016/j.jcyt.2021.02.111 Text en Copyright © 2021 Published by Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle 104
Senegaglia, AC
Rebelatto, CLK
Franck, CL
Lima, JS
Daga, DR
Shigunov, P
Azambuja, AP
Bana, EG
Marsaro, DB
Schaidt, B
Micosky, A
Jamur, VR
Vaz, IM
Schluga, Y
Leite, LMB
Ribeiro, LL
Correa, A
Brofman, PRS
USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title_full USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title_fullStr USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title_full_unstemmed USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title_short USE OF TOCILIZUMAB AND MESENCHYMAL STROMAL CELLS IN THE TREATMENT OF SEVERE COVID-19 - A CASE REPORT
title_sort use of tocilizumab and mesenchymal stromal cells in the treatment of severe covid-19 - a case report
topic 104
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079859/
http://dx.doi.org/10.1016/j.jcyt.2021.02.111
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