Metabolomics study of COVID-19 patients in four different clinical stages

Producción CientíficaSARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARS-CoV-2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC–QTOF–MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to “normal” values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.Consejo Superior de Investigaciones Científcas (grants CSIC-COV19-016/202020E155, SGL21-03-026 and SGL2021-03-038)Junta de Castilla y León (projects COVID 07.04.467B04.74011.0 and CLU-2029-02)Ministerio de Economía, Industria y Competitividad (project AGL2017-89417-R)Ministerio de Ciencia, Innovación y Universidades (contract IJC2018-037560-I

Is it true coeliacs do not digest gliadin ?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

Prolyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

Producción CientíficaBackground: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.Ministerio de Ciencia, Innovación y Universidades (project RTI2018-095672-B-I00)Instituto de Salud Carlos III - Fondo de Investigación Sanitaria (grants PI15/00531 and PI19/01410)Fundació La Marató TV3 (grants 20153030 and 20153031)Consejo Superior de Investigaciones Científicas (project CSIC-COV19-016/202020E155)Junta de Castilla y León (project 07.04.467B04.74011.0

Patrones de marcaje visual en el oso pardo: un enfoque experimental

XV Congreso de la Sociedad Española para la Conservación y Estudio de los Mamíferos (SECEM), Córdoba, 4-7 diciembre de 2021.Peer reviewe

HGF, IL-1α, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients

Producción CientíficaPneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95–6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07–1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39–0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.Instituto de Salud Carlos III (grant COV20/00491

Evaluation of cytokines as robust diagnostic biomarkers for COVID-19 detection

Producción CientíficaAntigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery–validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines’ quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933–0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127–80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846–0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover–validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.Instituto de Salud Carlos III (grant COV20/00491)Consejo Superior de Investigaciones científicas (grant CSIC-COV19-016/202020E155)Junta de Castilla y León (project COVID 07.04.467B04.74011.0)IBGM excellence programme (grant CLU-2029-02

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can

Producción CientíficaSevere status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064–8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540–50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.Instituto de Salud Carlos III (grant COV20/00491)Junta de Castilla y León (grant 18IGOF

Interacciones innato-adaptativas en el sistema inmune y su relación con la patogenia de la enfermedad celiaca

Departamento de Pediatría e Inmunología, Obstetricia y Ginecología, Nutrición y Bromatología, Psiquiatría e Historia de la CienciaDoctorado en investigación básica y clínica en pediatría, inmunología, obstetricia-ginecología y nutrición-bromatologí

Is celiac disease really associated with inflammatory bowel disease?

Producción CientíficaLa enfermedad celiaca (ECe) y la enfermedad inflamatoria intestinal (EII) son dolencias crónicas gastrointestinales de origen inflamatorio que se desarrollan en respuesta a agentes desencadenantes ambientales en individuos genéticamente predispuestos (1,2). La ECe está focalizada en la mucosa duodenal, donde se desarrolla una intolerancia al gluten de la dieta, procedente del trigo, la cebada, el centeno y algunas variedades de avena (3-5). En cuanto a la EII, se subdivide principalmente en enfermedad de Crohn (EC) y colitis, siendo la colitis ulcerosa (CU) la más estudiada. Mientras que la EC se puede encontrar a lo largo de todo el tracto gastrointestinal –aunque con mayor frecuencia en íleon y colon–, la CU se focaliza en el colon (6-8). A diferencia de la ECe, se desconoce el desencadenante de la EII, pero el desequilibrio de la microbiota intestinal parece tener un papel fundamental en su patogenia (9). En relación a la genética, los individuos con ECe portan las variantes DQ2 o DQ8 del antígeno leucocitario humano (HLA, por sus siglas en inglés), que promueven una unión altamente afín de péptidos derivados del gluten (2), mientras que los pacientes con EII pueden portar dos o más variantes (R702W, G908R y/o L1007fs) que provocan la pérdida de función del gen CARD15 (10,11), codificante del dominio de oligomerización y unión de nucleótidos (NOD) 2, importante en el reconocimiento de péptidos bacterianos y procesos autofágicos (12)