Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.
Identifieur interne : 001935 ( Main/Exploration ); précédent : 001934; suivant : 001936Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.
Auteurs : Fermín Sánchez-Guijo [Espagne] ; Mariano García-Arranz [Espagne] ; Miriam L Pez-Parra [Espagne] ; Pablo Monedero [Espagne] ; Carmen Mata-Martínez [Espagne] ; Arnoldo Santos [Espagne] ; Víctor Sagredo [Espagne] ; José-Manuel Álvarez-Avello [Espagne] ; José Eugenio Guerrero [Espagne] ; César Pérez-Calvo [Espagne] ; Miguel-Vicente Sánchez-Hernández [Espagne] ; José Luis Del-Pozo [Espagne] ; Enrique J. Andreu [Espagne] ; María-Eugenia Fernández-Santos [Espagne] ; Barbara Soria-Juan [Espagne] ; Luis M. Hernández-Blasco [Espagne] ; Etelvina Andreu [Espagne] ; José M. Sempere [Espagne] ; Agustín G. Zapata [Espagne] ; José M. Moraleda [Espagne] ; Bernat Soria [Espagne] ; Francisco Fernández-Avilés [Espagne] ; Damián García-Olmo [Espagne] ; Felipe Pr Sper [Espagne]Source :
- EClinicalMedicine [ 2589-5370 ] ; 2020.
Abstract
Background
Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.
Methods
Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10
Findings
First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.
Interpretation
Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.
Funding
None.
DOI: 10.1016/j.eclinm.2020.100454
PubMed: 32838232
PubMed Central: PMC7348610
Affiliations:
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<author><name sortKey="Soria Juan, Barbara" sort="Soria Juan, Barbara" uniqKey="Soria Juan B" first="Barbara" last="Soria-Juan">Barbara Soria-Juan</name>
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<author><name sortKey="Hernandez Blasco, Luis M" sort="Hernandez Blasco, Luis M" uniqKey="Hernandez Blasco L" first="Luis M" last="Hernández-Blasco">Luis M. Hernández-Blasco</name>
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<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
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<author><name sortKey="Andreu, Etelvina" sort="Andreu, Etelvina" uniqKey="Andreu E" first="Etelvina" last="Andreu">Etelvina Andreu</name>
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<author><name sortKey="Sempere, Jose M" sort="Sempere, Jose M" uniqKey="Sempere J" first="José M" last="Sempere">José M. Sempere</name>
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<author><name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
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<affiliation wicri:level="3"><nlm:affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
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<wicri:regionArea>Department of Cell Biology, Universidad Complutense, Madrid</wicri:regionArea>
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<author><name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
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<affiliation wicri:level="1"><nlm:affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</nlm:affiliation>
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<author><name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
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<affiliation wicri:level="1"><nlm:affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</nlm:affiliation>
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<author><name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
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<affiliation wicri:level="3"><nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine, Universidad Complutense, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<author><name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
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<country xml:lang="fr">Espagne</country>
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<region nuts="2" type="region">Communauté de Madrid</region>
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<affiliation wicri:level="3"><nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<affiliation wicri:level="4"><nlm:affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
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<date when="2020">2020</date>
<idno type="RBID">pubmed:32838232</idno>
<idno type="pmid">32838232</idno>
<idno type="doi">10.1016/j.eclinm.2020.100454</idno>
<idno type="pmc">PMC7348610</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.</title>
<author><name sortKey="Sanchez Guijo, Fermin" sort="Sanchez Guijo, Fermin" uniqKey="Sanchez Guijo F" first="Fermín" last="Sánchez-Guijo">Fermín Sánchez-Guijo</name>
<affiliation wicri:level="1"><nlm:affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca</wicri:regionArea>
<wicri:noRegion>Salamanca</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Garcia Arranz, Mariano" sort="Garcia Arranz, Mariano" uniqKey="Garcia Arranz M" first="Mariano" last="García-Arranz">Mariano García-Arranz</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
<author><name sortKey="L Pez Parra, Miriam" sort="L Pez Parra, Miriam" uniqKey="L Pez Parra M" first="Miriam" last="L Pez-Parra">Miriam L Pez-Parra</name>
<affiliation wicri:level="1"><nlm:affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca</wicri:regionArea>
<wicri:noRegion>Salamanca</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Monedero, Pablo" sort="Monedero, Pablo" uniqKey="Monedero P" first="Pablo" last="Monedero">Pablo Monedero</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mata Martinez, Carmen" sort="Mata Martinez, Carmen" uniqKey="Mata Martinez C" first="Carmen" last="Mata-Martínez">Carmen Mata-Martínez</name>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Santos, Arnoldo" sort="Santos, Arnoldo" uniqKey="Santos A" first="Arnoldo" last="Santos">Arnoldo Santos</name>
<affiliation wicri:level="3"><nlm:affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>CIBER de Enfermedades Respiratorias CIBERES, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER de Enfermedades Respiratorias CIBERES, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sagredo, Victor" sort="Sagredo, Victor" uniqKey="Sagredo V" first="Víctor" last="Sagredo">Víctor Sagredo</name>
<affiliation wicri:level="1"><nlm:affiliation>Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca</wicri:regionArea>
<wicri:noRegion>Salamanca</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Alvarez Avello, Jose Manuel" sort="Alvarez Avello, Jose Manuel" uniqKey="Alvarez Avello J" first="José-Manuel" last="Álvarez-Avello">José-Manuel Álvarez-Avello</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Guerrero, Jose Eugenio" sort="Guerrero, Jose Eugenio" uniqKey="Guerrero J" first="José Eugenio" last="Guerrero">José Eugenio Guerrero</name>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Perez Calvo, Cesar" sort="Perez Calvo, Cesar" uniqKey="Perez Calvo C" first="César" last="Pérez-Calvo">César Pérez-Calvo</name>
<affiliation wicri:level="3"><nlm:affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sanchez Hernandez, Miguel Vicente" sort="Sanchez Hernandez, Miguel Vicente" uniqKey="Sanchez Hernandez M" first="Miguel-Vicente" last="Sánchez-Hernández">Miguel-Vicente Sánchez-Hernández</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca</wicri:regionArea>
<wicri:noRegion>Salamanca</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Del Pozo, Jose Luis" sort="Del Pozo, Jose Luis" uniqKey="Del Pozo J" first="José Luis" last="Del-Pozo">José Luis Del-Pozo</name>
<affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra</wicri:regionArea>
<wicri:noRegion>Clínica Universidad de Navarra</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Andreu, Enrique J" sort="Andreu, Enrique J" uniqKey="Andreu E" first="Enrique J" last="Andreu">Enrique J. Andreu</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Soria Juan, Barbara" sort="Soria Juan, Barbara" uniqKey="Soria Juan B" first="Barbara" last="Soria-Juan">Barbara Soria-Juan</name>
<affiliation wicri:level="3"><nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hernandez Blasco, Luis M" sort="Hernandez Blasco, Luis M" uniqKey="Hernandez Blasco L" first="Luis M" last="Hernández-Blasco">Luis M. Hernández-Blasco</name>
<affiliation wicri:level="1"><nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Andreu, Etelvina" sort="Andreu, Etelvina" uniqKey="Andreu E" first="Etelvina" last="Andreu">Etelvina Andreu</name>
<affiliation wicri:level="1"><nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sempere, Jose M" sort="Sempere, Jose M" uniqKey="Sempere J" first="José M" last="Sempere">José M. Sempere</name>
<affiliation wicri:level="1"><nlm:affiliation>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Cell Biology, Universidad Complutense, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia</wicri:regionArea>
<wicri:noRegion>Murcia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
<affiliation wicri:level="1"><nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Institute of Bioengineering, Universidad Miguel Hernández, Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine, Universidad Complutense, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
<affiliation wicri:level="3"><nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">EClinicalMedicine</title>
<idno type="eISSN">2589-5370</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><b>Background</b>
</p>
<p>Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>Methods</b>
</p>
<p>Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10</p>
</div>
<div type="abstract" xml:lang="en"><p><b>Findings</b>
</p>
<p>First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>Interpretation</b>
</p>
<p>Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>Funding</b>
</p>
<p>None.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32838232</PMID>
<DateRevised><Year>2021</Year>
<Month>01</Month>
<Day>27</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2589-5370</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>25</Volume>
<PubDate><Year>2020</Year>
<Month>Aug</Month>
</PubDate>
</JournalIssue>
<Title>EClinicalMedicine</Title>
<ISOAbbreviation>EClinicalMedicine</ISOAbbreviation>
</Journal>
<ArticleTitle>Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.</ArticleTitle>
<Pagination><MedlinePgn>100454</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.eclinm.2020.100454</ELocationID>
<Abstract><AbstractText Label="Background" NlmCategory="UNASSIGNED">Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.</AbstractText>
<AbstractText Label="Methods" NlmCategory="UNASSIGNED">Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10<sup>6</sup>
(IQR 0.50 × 10<sup>6</sup>
) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.</AbstractText>
<AbstractText Label="Findings" NlmCategory="UNASSIGNED">First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.</AbstractText>
<AbstractText Label="Interpretation" NlmCategory="UNASSIGNED">Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.</AbstractText>
<AbstractText Label="Funding" NlmCategory="UNASSIGNED">None.</AbstractText>
<CopyrightInformation>© 2020 The Authors.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sánchez-Guijo</LastName>
<ForeName>Fermín</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>García-Arranz</LastName>
<ForeName>Mariano</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>López-Parra</LastName>
<ForeName>Miriam</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Monedero</LastName>
<ForeName>Pablo</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mata-Martínez</LastName>
<ForeName>Carmen</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Santos</LastName>
<ForeName>Arnoldo</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>CIBER de Enfermedades Respiratorias CIBERES, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sagredo</LastName>
<ForeName>Víctor</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Álvarez-Avello</LastName>
<ForeName>José-Manuel</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guerrero</LastName>
<ForeName>José Eugenio</ForeName>
<Initials>JE</Initials>
<AffiliationInfo><Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pérez-Calvo</LastName>
<ForeName>César</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sánchez-Hernández</LastName>
<ForeName>Miguel-Vicente</ForeName>
<Initials>MV</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Del-Pozo</LastName>
<ForeName>José Luis</ForeName>
<Initials>JL</Initials>
<AffiliationInfo><Affiliation>Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Andreu</LastName>
<ForeName>Enrique J</ForeName>
<Initials>EJ</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fernández-Santos</LastName>
<ForeName>María-Eugenia</ForeName>
<Initials>ME</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Soria-Juan</LastName>
<ForeName>Barbara</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hernández-Blasco</LastName>
<ForeName>Luis M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Andreu</LastName>
<ForeName>Etelvina</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sempere</LastName>
<ForeName>José M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zapata</LastName>
<ForeName>Agustín G</ForeName>
<Initials>AG</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Moraleda</LastName>
<ForeName>José M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Soria</LastName>
<ForeName>Bernat</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fernández-Avilés</LastName>
<ForeName>Francisco</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>García-Olmo</LastName>
<ForeName>Damián</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Prósper</LastName>
<ForeName>Felipe</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>07</Month>
<Day>10</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>EClinicalMedicine</MedlineTA>
<NlmUniqueID>101733727</NlmUniqueID>
<ISSNLinking>2589-5370</ISSNLinking>
</MedlineJournalInfo>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">Case series</Keyword>
<Keyword MajorTopicYN="N">Cellular therapy</Keyword>
<Keyword MajorTopicYN="N">Mechanical ventilation</Keyword>
<Keyword MajorTopicYN="N">Mesenchymal stromal cells</Keyword>
<Keyword MajorTopicYN="N">Pneumonia</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
</KeywordList>
<CoiStatement>Dr. Sanchez-Guijo reports grants and personal fees from Novartis, personal fees from BMS, Pfizer, Incyte, Gilead, Roche and Amgen, outside the submitted work; Dr. López-Parra reports personal fees from Gilead, Novartis, BMS and Janssen, outside the submitted work. Dr. JL del Pozo reports grants from Novartis and personal fees from Novartis, Pfizer, Gilead and Roche, outside the submitted work; Dr. Moraleda reports personal fees and other from Gilead, grants and personal fees from Jazz Pharma, and personal fees from Novartis and from Sandoz, outside the submitted work. Dr. García-Olmo has received personal fees from Takeda, outside the submitted work; Dr. Prosper reports personal fees from Oryzon Genomics, and from Janssen, outside the submitted work; Dr. García-Arranz and Dr. García-Olmo have applied for two patents related with this study entitled “Identification and isolation of multipotent cells from nonosteochondral mesenchymal tissue” (WO 2006/057649) and “Use of adipose tissue-derived stromal stem cells in treating fistula” (WO 2006/136244), and both are shareholders of Biosurgery, an educational company providing services to Takeda. All other authors declare no conflict of interest.</CoiStatement>
</MedlineCitation>
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<Month>05</Month>
<Day>28</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>06</Month>
<Day>23</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>06</Month>
<Day>24</Day>
</PubMedPubDate>
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<Month>8</Month>
<Day>25</Day>
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<affiliations><list><country><li>Espagne</li>
</country>
<region><li>Communauté de Madrid</li>
</region>
<settlement><li>Madrid</li>
</settlement>
<orgName><li>Université autonome de Madrid</li>
</orgName>
</list>
<tree><country name="Espagne"><noRegion><name sortKey="Sanchez Guijo, Fermin" sort="Sanchez Guijo, Fermin" uniqKey="Sanchez Guijo F" first="Fermín" last="Sánchez-Guijo">Fermín Sánchez-Guijo</name>
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<name sortKey="Alvarez Avello, Jose Manuel" sort="Alvarez Avello, Jose Manuel" uniqKey="Alvarez Avello J" first="José-Manuel" last="Álvarez-Avello">José-Manuel Álvarez-Avello</name>
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<name sortKey="Andreu, Etelvina" sort="Andreu, Etelvina" uniqKey="Andreu E" first="Etelvina" last="Andreu">Etelvina Andreu</name>
<name sortKey="Del Pozo, Jose Luis" sort="Del Pozo, Jose Luis" uniqKey="Del Pozo J" first="José Luis" last="Del-Pozo">José Luis Del-Pozo</name>
<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
<name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
<name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
<name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
<name sortKey="Garcia Arranz, Mariano" sort="Garcia Arranz, Mariano" uniqKey="Garcia Arranz M" first="Mariano" last="García-Arranz">Mariano García-Arranz</name>
<name sortKey="Garcia Arranz, Mariano" sort="Garcia Arranz, Mariano" uniqKey="Garcia Arranz M" first="Mariano" last="García-Arranz">Mariano García-Arranz</name>
<name sortKey="Garcia Arranz, Mariano" sort="Garcia Arranz, Mariano" uniqKey="Garcia Arranz M" first="Mariano" last="García-Arranz">Mariano García-Arranz</name>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<name sortKey="Guerrero, Jose Eugenio" sort="Guerrero, Jose Eugenio" uniqKey="Guerrero J" first="José Eugenio" last="Guerrero">José Eugenio Guerrero</name>
<name sortKey="Hernandez Blasco, Luis M" sort="Hernandez Blasco, Luis M" uniqKey="Hernandez Blasco L" first="Luis M" last="Hernández-Blasco">Luis M. Hernández-Blasco</name>
<name sortKey="L Pez Parra, Miriam" sort="L Pez Parra, Miriam" uniqKey="L Pez Parra M" first="Miriam" last="L Pez-Parra">Miriam L Pez-Parra</name>
<name sortKey="L Pez Parra, Miriam" sort="L Pez Parra, Miriam" uniqKey="L Pez Parra M" first="Miriam" last="L Pez-Parra">Miriam L Pez-Parra</name>
<name sortKey="L Pez Parra, Miriam" sort="L Pez Parra, Miriam" uniqKey="L Pez Parra M" first="Miriam" last="L Pez-Parra">Miriam L Pez-Parra</name>
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<name sortKey="Monedero, Pablo" sort="Monedero, Pablo" uniqKey="Monedero P" first="Pablo" last="Monedero">Pablo Monedero</name>
<name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
<name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
<name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
<name sortKey="Perez Calvo, Cesar" sort="Perez Calvo, Cesar" uniqKey="Perez Calvo C" first="César" last="Pérez-Calvo">César Pérez-Calvo</name>
<name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
<name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
<name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
<name sortKey="Sagredo, Victor" sort="Sagredo, Victor" uniqKey="Sagredo V" first="Víctor" last="Sagredo">Víctor Sagredo</name>
<name sortKey="Sanchez Guijo, Fermin" sort="Sanchez Guijo, Fermin" uniqKey="Sanchez Guijo F" first="Fermín" last="Sánchez-Guijo">Fermín Sánchez-Guijo</name>
<name sortKey="Sanchez Guijo, Fermin" sort="Sanchez Guijo, Fermin" uniqKey="Sanchez Guijo F" first="Fermín" last="Sánchez-Guijo">Fermín Sánchez-Guijo</name>
<name sortKey="Sanchez Hernandez, Miguel Vicente" sort="Sanchez Hernandez, Miguel Vicente" uniqKey="Sanchez Hernandez M" first="Miguel-Vicente" last="Sánchez-Hernández">Miguel-Vicente Sánchez-Hernández</name>
<name sortKey="Santos, Arnoldo" sort="Santos, Arnoldo" uniqKey="Santos A" first="Arnoldo" last="Santos">Arnoldo Santos</name>
<name sortKey="Santos, Arnoldo" sort="Santos, Arnoldo" uniqKey="Santos A" first="Arnoldo" last="Santos">Arnoldo Santos</name>
<name sortKey="Sempere, Jose M" sort="Sempere, Jose M" uniqKey="Sempere J" first="José M" last="Sempere">José M. Sempere</name>
<name sortKey="Soria Juan, Barbara" sort="Soria Juan, Barbara" uniqKey="Soria Juan B" first="Barbara" last="Soria-Juan">Barbara Soria-Juan</name>
<name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
<name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
<name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
<name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
</country>
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