Aguado García, José María

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First Name
José María
Last Name
Aguado García
Universidad Complutense de Madrid
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Now showing 1 - 4 of 4
  • Publication
    Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19
    (MPDI, 2022-03-09) García Ríos, Estéfani; Leivas, Alejandra; Mancebo, Francisco J.; Sánchez Vega, Laura; Lanzarot, Diego; Aguado García, José María; Martínez López, Joaquín; Paciello, María Liz; Pérez Romero, Pilar
    In order to demonstrate the feasibility of preparing clinical-grade SARS-CoV-2-specific T-cells from convalescent donors and the ability of these cells to neutralize the virus in vitro, we used blood collected from two COVID-19 convalescent donors (before and after vaccination) that was stimulated with specific SARS-CoV-2 peptides followed by automated T-cell isolation using the CliniMacs Prodigy medical device. To determine cytotoxic activity, HEK 293T cells were transfected to express the SARS-CoV-2 M protein, mimicking SARS-CoV-2 infection. We were able to quickly and efficiently isolate SARS-CoV-2-specific T lymphocytes from both donors before and after they received the Pfizer-BioNTech vaccine. Althoughbefore vaccination, the final product contained up to 7.42% and 30.19% of IFN-γ+ CD3+ T-cells from donor 1 and donor 2, respectively, we observed an enrichment of the IFN-γ+ CD3+ T-cells after vaccination, reaching 70.47% and 42.59%, respectively. At pre-vaccination, the isolated SARS-CoV-2-specific T-cells exhibited cytotoxic activity that was significantly higher than that of unstimulated controls (donor 2: 15.41%, p-value 3.27 × 10−3). The cytotoxic activity of the isolated SARS-CoV-2-specific T-cells also significantly increased after vaccination (donor 1: 32.71%, p-value 1.44 × 10−5; donor 2: 33.38%, p-value 3.13 × 10−6). In conclusion, we demonstrated that SARS-CoV-2-specific T-cells can quickly and efficiently be stimulated from the blood of convalescent donors using SARS-CoV-2-specific peptides followed by automated isolation. Vaccinated convalescent donors have a higher percentage of SARS-CoV-2-specific T-cells and may be more suitable as donors. Although further studies are needed to assess the clinical utility of the functional isolated SARS-CoV-2-specific T-cells in patients, previous studies using the same stimulation and isolation methods applied to other pathologies support this idea.
  • Publication
    Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery
    (MDPI, 2021-09-10) Utrero Rico, Alberto; González Cuadrado, Cecilia; Chivite Lacaba, Marta; Cabrera Marante, Oscar; Laguna Goya, Rocío; Almendro Vazquez, Patricia; Díaz Pedroche, Carmen; Ruiz Ruigómez, María; Lalueza Blanco, Antonio; Folgueira López, María Dolores; Vázquez, Enrique; Quintas, Ana; Berges Buxeda, Marcos J.; Martín Rodriguez, Moisés; Dopazo, Ana; Serrano Hernández, Antonio; Aguado García, José María; Paz Artal, Estela
    An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.
  • Publication
    Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia
    (MPDI, 2022-03-29) Albasanz Puig, Adaia; Durà Miralles, Xavier; Laporte Amargós, Júlia; Mussetti, Alberto; Ruiz Camps, Isabel; Puerta Alcalde, Pedro; Abdala, Edson; Oltolini, Chiara; Akova, Murat; Montejo, José Miguel; Mikulska, Malgorzata; Martín Dávila, Pilar; Herrera, Fabián; Gasch, Oriol; Drgona, Lubos; Morales, Hugo Manuel Paz; Brunel, Anne-Sophie; García, Estefanía; Isler, Burcu; Kern, Winfried V.; Retamar Gentil, Pilar; Aguado García, José María; Montero, Milagros; Kanj, Souha S.; Sipahi, Oguz R.; Calik, Sebnem; Márquez Gómez, Ignacio; Marin, Jorge I.; Gomes, Marisa Z. R.; Hemmati, Philipp; Araos, Rafael; Peghin, Maddalena; Pozo, José Luis del; Yáñez, Lucrecia; Tilley, Robert; Manzur, Adriana; Novo, Andres; Pallarès, Natàlia; Bergas, Alba; Carratalà, Jordi; Gudiol, Carlota
    To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006–2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01–2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27–0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76–2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.
  • Publication
    A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID
    (MPDI, 2021-10-26) Utrero Rico, Alberto; Ruiz Ruigómez, María; Laguna Goya, Rocío; Arrieta Ortubay, Estíbaliz; Chivite Lacaba, Marta; González Cuadrado, Cecilia; Lalueza Blanco, Antonio; Almendro Vazquez, Patricia; Serrano, Antonio; Aguado García, José María; Lumbreras Bermejo, Carlos Juan; Paz Artal, Estela
    Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.