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Background: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time. Methods: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March–30 September 2020). Findings: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend (p for trend 700 ng/mL (OR 2.3, CI 1.3–4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5–3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5–4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04–1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65–0.98) was significantly associated with lower mortality. Interpretation: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care. Funding: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII. Resumen: Contexto: Nuestro objetivo es describir los cambios en las características y las estrategias de tratamiento de los pacientes hospitalizados por COVID-19, y detallar la tendencia de la mortalidad en el tiempo. Métodos: Estudio observacional de cohortes de todos los pacientes consecutivos, ingresados por COVID-19 durante más de 48 horas, en el Hospital Clínic de Barcelona (del 1 de marzo al 30 de septiembre de 2020). Resultados: Un total de 1645 pacientes consecutivos fueron evaluados durante un período de 7 meses. La mortalidad global (≤30 días) fue del 9.7% (159 pacientes): 7.7% en pacientes hospitalizados en salas convencionales, y 16.7% en pacientes que requirieron ingreso en UCI. La mortalidad global disminuyó del 11.6% en el primer mes al 1.4% en el último mes evaluado, reflejando una progresiva y significativa tendencia a la baja (p para la tendencia 700 ng/mL (OR 2.3; CI 1.3–4.1), ferritina>489 ng/mL (OR 1.9; CI 1.5–3.2), PCR>7 mg/dL (OR 2.6; CI 1.5–4.6), y una menor duración desde el inicio de síntomas a la hospitalización (OR 1.11; CI 1.04–1.17) fueron factores asociados a la mortalidad intrahospitalaria a 30 días. Por el contrario, el ingreso hospitalario previo en los últimos meses (OR 0.80; CI 0.65–0.98) se asoció significativamente a una menor mortalidad. Discusión: La mortalidad intrahospitalaria ha disminuido en los pacientes con COVID-19 durante los últimos meses, incluso siendo similares las características de los pacientes. Algunos cambios realizados en el manejo de estos pacientes podrían explicar esta tendencia decreciente. Nuestro estudio aporta datos actualizados en la mortalidad de los pacientes hospitalizados con COVID-19, que podrían ser útiles de cara a establecer unos cuidados estándar de calidad. Financiación: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme, EDRD. PPA [CM18/00132], NGP [FI19/00133] y CGV [FIS PI18/01061], han recibido becas del Ministerio de Sanidad y Consumo, ISCIII.

Background: Clinical features of Clostridium difficile infection (CDI) cases diagnosed by detection of polymerase chain reaction (PCR), with negative toxin enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of this study was to determine the magnitude of CDI patients who had negative EIA toxin determinations but positive PCR tests, and their differences in clinical presentation. Methods: We performed a retrospective study comparing the clinical features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR (toxin negative, PCR positive) over a 16-month period. Only patients with an initial Clostridium difficile infection episode that fulfilled a standardized definition were included. Results: During the study period, 107 episodes of CDI were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three patients (31%) had GDH positive, negative toxin EIA and positive PCR determination (PCR positive patients). PCR positive patients were younger, 57 (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001). Fewer PCR positive patients were receiving proton pump inhibitors (21 patients, 64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical presentation was similar in both groups. In the multivariate analysis, lower age was identified as the only independent variable associated with PCR positive patients. Conclusions: One third of Clostridium difficile infection patients present negative toxin EIA and PCR positive tests. Performing PCR determination after the negative EIA test is more relevant in younger patients.

Objective: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare., Methods: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab., Results: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%)., Conclusions: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time., Methods: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020)., Findings: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend ( p for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality., Interpretation: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care., Funding: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII., Competing Interests: This research is part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Programme. This study has been co-funded by the European Regional Development Fund (EDRD). All authors report grants from EIT Health and the European Regional Development Fund (for themselves or their institution), during the conduct of the study. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061] have received research grants from the Ministerio de Sanidad y Consumo and Instituto de Salud Carlos III. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CGV has received honoraria for talks on behalf of Gilead Science, MSD, Novartis, Pfizer, Janssen, and Lilly, as well as a grant from Gilead Science and MSD. PPA has received honoraria for talks on behalf of Gilead Science and MSD. JM has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini, as well as grant support from Pfizer. Other authors do not declare conflict of interest outside the submitted work. Hospital Clinic of Barcelona COVID-19 Researchers: Infectious Diseases’ Research Group: Albiach L, Agüero D, Ambrosioni J, Blanco JL, De la Mora L, González-Cordón A, Inciarte A, Jordan C, Laguno M, Leal L, Lopera C, Macaya I, Mallolas J, Martínez E, Martínez M, Miró JM, Moreno A, Rojas J, Solá M, Torres B, Torres M, and all the staff members. Medical Intensive Care Unit: Adrian Téllez, Sara Fernández, and all the staff members. Department of International Health: Daniel Camprubi Ferrer, Maria Teresa de Alba, Marc Fernandez, Elisabet Ferrer, Berta Grau, Helena Marti, Magdalena Muelas, Maria Jesus Pinazo, Natalia Rodríguez, Montserrat Roldan, Carme Subira, Isabel Vera, Nana Williams, Jose Muñoz, and all the staff members. Department of Internal Medicine: Aldea A, Camafort M, Calvo J, Capdevila A, Cardellach F, Carbonell I, Coloma E, Foncillas A, Estruch R, Feliu M, Fernández-Solá J, Fuertes I, Gabara C, Grafia I, Ladino A, López-Alfaro R, López-Soto A, Masanés F, Matas A, Navarro M, Marco-Hernández J, Miguel L, Milisenda J, Moreno P, Naval J, Nicolás D, Oberoi H, Padrosa J, Prieto-González S, Pellicé M, Ribot J, Rodríguez-Núnez O, Sacanella E, Seguí F, Sierra C, Tomé A, Ugarte A, Ventosa H, Zamora-Martínez C, and all the staff members. Department of Microbiology: M. Almela, M. Alvarez, J. Bosch, C. Casals, J. Costa, G. Cuesta, M. Fernandez, B. Fidalgo, J. Gonzàlez, J.C. Hurtado, F. Marco, M.A. Marcos, M. Martínez, M. Mosquera, S. Narvaez, C. Pitart, E. Rubio, A. Vergara, M.E.Valls, J. Vila, Y. Zboromyrska and all the staff members. Department of Farmacy: E. López, D. Soy, M. Tuset and all the staff members. Data sharing statement: All data will be available under request after manuscript acceptance., (© 2021 Published by Elsevier Ltd.)

Background: Clinical features of Clostridium difficile infection (CDI) cases diagnosed by detection of polymerase chain reaction (PCR), with negative toxin enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of this study was to determine the magnitude of CDI patients who had negative EIA toxin determinations but positive PCR tests, and their differences in clinical presentation., Methods: We performed a retrospective study comparing the clinical features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR (toxin negative, PCR positive) over a 16-month period. Only patients with an initial Clostridium difficile infection episode that fulfilled a standardized definition were included., Results: During the study period, 107 episodes of CDI were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three patients (31%) had GDH positive, negative toxin EIA and positive PCR determination (PCR positive patients). PCR positive patients were younger, 57 (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001). Fewer PCR positive patients were receiving proton pump inhibitors (21 patients, 64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical presentation was similar in both groups. In the multivariate analysis, lower age was identified as the only independent variable associated with PCR positive patients., Conclusions: One third of Clostridium difficile infection patients present negative toxin EIA and PCR positive tests. Performing PCR determination after the negative EIA test is more relevant in younger patients.