Person: Aguado García, José María
Universidad Complutense de Madrid
Faculty / Institute
Now showing 1 - 4 of 4
PublicationIsolation 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, PilarIn 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. PublicationAlterations 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, EstelaAn 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. PublicationEffect 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, CarlotaTo 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. PublicationA 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, EstelaDespite 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.