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1. Metabolomic profile of severe COVID-19 and a signature predictive of progression towards severe disease status: a prospective cohort study (METCOVID)

Author

Roger Mallol, Alexander Rombauts, Gabriela Abelenda-Alonso, Carlota Gudiol, Marc Balsalobre, and Jordi Carratalà

Subjects
SARS-CoV-2, COVID-19, Prognosis, Severity, Metabolomics, NMR, Medicine, Science
Abstract

Abstract Profound metabolomic alterations occur during COVID-19. Early identification of the subset of hospitalised COVID-19 patients at risk of developing severe disease is critical for optimal resource utilization and prompt treatment. This work explores the metabolomic profile of hospitalised adult COVID-19 patients with severe disease, and establishes a predictive signature for disease progression. Within 48 hours of admission, serum samples were collected from 148 hospitalised patients for nuclear magnetic resonance (NMR) spectroscopy. Lipoprotein profiling was performed using the 1H-NMR-based Liposcale test, while low molecular weight metabolites were analysed using one-dimensional Carr-Purcell-Meiboom-Gill pulse spectroscopy and an adaptation of the Dolphin method for lipophilic extracts. Severe COVID-19, per WHO’s Clinical Progression Scale, was characterized by altered lipoprotein distribution, elevated signals of glyc-A and glyc-B, a shift towards a catabolic state with elevated levels of branched-chain amino acids, and accumulation of ketone bodies. Furthermore, COVID-19 patients initially presenting with moderate disease but progressing to severe stages exhibited a distinct metabolic signature. Our multivariate model demonstrated a cross-validated AUC of 0.82 and 72% predictive accuracy for severity progression. NMR spectroscopy-based metabolomic profiling enables the identification of moderate COVID-19 patients at risk of disease progression, aiding in resource allocation and early intervention.

Published
2025
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2. Severe ARDS due to disseminated toxoplasmosis in a person with HIV successfully treated with ECMO: a case report

Author

Daniel Medina, Renzo Ávila, Graciela Rodríguez-Sevilla, Víctor Gumucio, María Bonilla, Gabriela Abelenda-Alonso, Jordi Niubó, Maria Saumoy, Juan Tiraboschi, María Paz Fuset, and Arkaitz Imaz

Subjects
disseminated toxoplasmosis, HIV, ARDS, ECMO, case report, Medicine (General), R5-920
Abstract

Disseminated toxoplasmosis (DT) is an uncommon but severe complication associated with acquired immunodeficiency syndrome (AIDS). This case report describes the successful treatment of a 28-year-old male individual with AIDS who developed severe and life-threatening acute respiratory distress syndrome (ARDS) resulting from DT, in which extracorporeal membrane oxygenation (ECMO) was employed effectively.

Published
2025
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3. Multiplex real-time PCR in non-invasive respiratory samples to reduce antibiotic use in community-acquired pneumonia: a randomised trial

Author

Gabriela Abelenda-Alonso, Laura Calatayud, Alexander Rombauts, Yolanda Meije, Isabel Oriol, Nieves Sopena, Ariadna Padullés, Jordi Niubó, Alejandra Duarte, Jaume Llaberia, Judit Aranda, Carlota Gudiol, Pau Satorra, Cristian Tebé, Carmen Ardanuy, and Jordi Carratalà

Subjects
Science
Abstract

Abstract We assessed whether multiplex real-time PCR plus conventional microbiological testing is safe and more effective than conventional microbiological testing alone for reducing antibiotic use in community-acquired pneumonia (CAP). In this randomised trial, we recruited adults hospitalised with CAP at four Spanish hospitals. Patients were randomly assigned (1:1) to undergo either multiplex real-time PCR in non-invasive respiratory samples plus conventional microbiological testing or conventional microbiological testing alone. The primary endpoint was antibiotic use measured by days of antibiotic therapy (DOT). Between February 20, 2020, and April 24, 2023, 242 patients were enrolled; 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. All but one of the patients allocated to multiplex real-time PCR plus conventional microbiological testing underwent PCR, which was performed in sputum samples in 77 patients (65.2%) and in nasopharyngeal swabs in 41 (34.7%). The median DOT was 10.04 (IQR 7.98, 12.94) in the multiplex PCR plus conventional microbiological testing group and 11.33 (IQR 8.15, 16.16) in the conventional microbiological testing alone group (difference −1.04; 95% CI, −2.42 to 0.17; p = 0.093). No differences were observed in adverse events and 30-day mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Clinicaltrials.gov registration: NCT04158492.

Published
2024
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4. SARS-CoV-2 infection induces robust mucosal antibody responses in the upper respiratory tract

Author

Alba Escalera, Amaya Rojo-Fernandez, Alexander Rombauts, Gabriela Abelenda-Alonso, Jordi Carratalà, Adolfo García-Sastre, and Teresa Aydillo

Subjects
Immunology, Science
Abstract

Summary: Despite multiple research efforts to characterize coronavirus disease 2019 (COVID-19) in humans, there is no clear data on the specific role of mucosal immunity on COVID-19 disease. Here, we longitudinally profile the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal HCoV-OC43 S proteins in serum and nasopharyngeal swabs from COVID-19 patients. Results showed that specific antibody responses against SARS-CoV-2 and HCoV-OC43 S proteins can be detected in the upper respiratory tract. We found that COVID-19 patients mounted a robust mucosal antibody response against SARS-CoV-2 S with specific secretory immunoglobulin A (sIgA), IgA, IgG, and IgM antibody subtypes detected in the nasal swabs. Additionally, COVID-19 patients showed IgG, IgA, and sIgA responses against HCoV-OC43 S in the local mucosa, whereas no specific IgM was detected. Interestingly, mucosal antibody titers against SARS-CoV-2 peaked at day 7, whereas HCoV-OC43 titers peaked earlier at day 3 post-recruitment, suggesting an immune memory recall to conserved epitopes of beta-HCoVs in the upper respiratory tract.

Published
2024
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5. SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study

Author

Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, and Guadalupe Gómez Melis

Subjects
COVID-19, Delta variant, Generalized odds-rate class of models, Incubation period, Infectious disease, Adenovirus-based vaccine, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. Methods We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. Results From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5–3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. Conclusions Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.

Published
2022
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6. An Ocean between the Waves: Trends in Antimicrobial Consumption in Hospitalized Patients with COVID-19

Author

Xavier Durà-Miralles, Gabriela Abelenda-Alonso, Alba Bergas, Júlia Laporte-Amargós, Enric Sastre-Escolà, Ariadna Padullés, Jordi Carratalà, and Carlota Gudiol

Subjects
COVID-19, antibiotic, pandemic, stewardship, Therapeutics. Pharmacology, RM1-950
Abstract

We assessed the antibiotic use in SARS-CoV-2-infected patients during four different waves of the COVID-19 pandemic, as well as its trends over the period and associated risk factors. We performed a cross-sectional retrospective analysis nested in a prospectively collected cohort of hospitalized adult patients with COVID-19 at a university hospital in Spain. A total of 2415 patients were included in this study, among whom 1120 corresponded to the first wave. The highest percentage of patients receiving some sort of antibiotic treatment was higher during the first wave (77.6%) than during the others; nevertheless, our calculation of the average DOT (days of antibiotic treatment) per 100 patient days of stay found that the highest antibiotic prescription rate corresponded to the second pandemic wave (61.61 DOT/100 patient days), which was associated with a higher ICU admission rate and a lower SpO2/FiO2 ratio at admission. After the second wave, the prescription rates presented a steady downward trend. With regard to the use of specific antibiotic families, amoxicillin/clavulanate was the most used antibiotic in our cohort (14.20 DOT/100 patient days) due to a high prescription rate during the first wave. According to the “AWaRe” WHO classification, antibiotics corresponding to the “Watch” group were the most prescribed (27.92 DOT/100 patient days). The antibiotic use rate fell progressively, but it remained high during all four waves analyzed. In conclusion, antibiotic use was high throughout all the waves that were analyzed, despite a relatively low incidence of bacterial coinfection and superinfection. Efforts should be made to keep antimicrobial stewardship programs active, especially in complicated epidemiological situations, such as the SARS-CoV-2 pandemic.

Published
2024
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7. Immunological imprinting of the antibody response in COVID-19 patients

Author

Teresa Aydillo, Alexander Rombauts, Daniel Stadlbauer, Sadaf Aslam, Gabriela Abelenda-Alonso, Alba Escalera, Fatima Amanat, Kaijun Jiang, Florian Krammer, Jordi Carratala, and Adolfo García-Sastre

Subjects
Science
Abstract

In addition to SARS-CoV-2, other coronaviruses also infect human, but whether consecutive infections cross-modulate the induced immune response is still unclear. Here the authors show that SARS-CoV-2 infection boosts pre-existing responses to other coronaviruses, yet such back-boosting hampers the induction of specific antibodies against SARS-CoV-2.

Published
2021
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8. Effect of albumin administration on outcomes in hypoalbuminemic patients hospitalized with community-acquired pneumonia (ALBUCAP): a prospective, randomized, phase III clinical controlled trial—a trial protocol

Author

Alexander Rombauts, Gabriela Abelenda-Alonso, Antonella Francesca Simonetti, Guillermo Verdejo, Yolanda Meije, Lucia Ortega, Mercedes Clemente, Jordi Niubó, Yolanda Ruiz, Carlota Gudiol, Cristian Tebé, Sebastian Videla, and Jordi Carratalà

Subjects
Community-acquired pneumonia, Albumin, Inflammation, Randomized controlled trial, Medicine (General), R5-920
Abstract

Abstract Background Community-acquired pneumonia (CAP) remains a leading cause of death worldwide, and hypoalbuminemia is associated with worse outcomes. However, it remains uncertain whether albumin administration could have any beneficial effects. We aim to assess whether the administration of albumin in hypoalbuminemic patients with CAP increases the proportion of clinically stable patients at day 5 compared with the standard of care alone. Methods This is a trial protocol for a superiority, non-blinded, multicenter, randomized, phase 3, interventional controlled clinical trial. The primary endpoint will be the proportion of clinical stable patients at day 5 (intention to treat), defined as those with stable vital signs for at least 24 h. The secondary endpoints will be time to clinical stability, duration of intravenous and total antibiotic treatment, length of hospital stay, intensive care unit admission, duration of mechanical ventilation and vasopressor treatment, adverse events, readmission within 30 days, and all-cause mortality. The trial has been approved by the Spanish Medicines and Healthcare Products Regulatory Agency. The investigators commit to publish the data in peer-reviewed journals within a year of the study completion date. Subjects will be recruited from three Spanish hospitals over a planned enrolment period of 2 years. A follow-up visit will be performed 1 month after discharge. We have estimated the need for a sample size of 360 patients at a two-sided 5% alpha-level with a power of 80% based on intention to treat. Eligible participants must be hospitalized, hypoalbuminemic (≤ 30 g/L), non-immunosuppressed, adults, and diagnosed with CAP. They will be randomly assigned (1:1) to receive standard care plus albumin (20 g in 100 mL) every 12 h for 4 days or standard care alone. Discussion If this randomized trial confirms the hypothesis, it should lead to a change in current clinical practice for the management of hypoalbuminemic patients with CAP. Trial registration European Clinical Trials Database (EudraCT) 2018-003117-18 . Registered on 12 April 2019. ClinicalTrials.gov NCT04071041 . Registered on 27 August 2019

Published
2020
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9. Dynamics of Gene Expression Profiling and Identification of High-Risk Patients for Severe COVID-19

Author

Alexander Rombauts, Marta Bódalo Torruella, Gabriela Abelenda-Alonso, Júlia Perera-Bel, Anna Ferrer-Salvador, Ariadna Acedo-Terrades, Maria Gabarrós-Subirà, Isabel Oriol, Carlota Gudiol, Lara Nonell, and Jordi Carratalà

Subjects
COVID-19, SARS-CoV-2, transcriptomics, ARDS, gene expression, prognosis, Biology (General), QH301-705.5
Abstract

The clinical manifestations of SARS-CoV-2 infection vary widely, from asymptomatic infection to the development of acute respiratory distress syndrome (ARDS) and death. The host response elicited by SARS-CoV-2 plays a key role in determining the clinical outcome. We hypothesized that determining the dynamic whole blood transcriptomic profile of hospitalized adult COVID-19 patients and characterizing the subgroup that develops severe disease and ARDS would broaden our understanding of the heterogeneity in clinical outcomes. We recruited 60 hospitalized patients with RT-PCR-confirmed SARS-CoV-2 infection, among whom 19 developed ARDS. Peripheral blood was collected using PAXGene RNA tubes within 24 h of admission and on day 7. There were 2572 differently expressed genes in patients with ARDS at baseline and 1149 at day 7. We found a dysregulated inflammatory response in COVID-19 ARDS patients, with an increased expression of genes related to pro-inflammatory molecules and neutrophil and macrophage activation at admission, in addition to an immune regulation loss. This led, in turn, to a higher expression of genes related to reactive oxygen species, protein polyubiquitination, and metalloproteinases in the latter stages. Some of the most significant differences in gene expression found between patients with and without ARDS corresponded to long non-coding RNA involved in epigenetic control.

Published
2023
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10. Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia

Author

Diego Viasus, Antonella F. Simonetti, Lara Nonell, Oscar Vidal, Yolanda Meije, Lucía Ortega, Magdalena Arnal, Marta Bódalo-Torruella, Montserrat Sierra, Alexander Rombauts, Gabriela Abelenda-Alonso, Gemma Blanchart, Carlota Gudiol, and Jordi Carratalà

Subjects
community-acquired pneumonia, mortality, gene expression profile, gene set enrichment analysis, Biology (General), QH301-705.5
Abstract

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein–protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

Published
2023
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11. Blood Hemoglobin Substantially Modulates the Impact of Gender, Morbid Obesity, and Hyperglycemia on COVID-19 Death Risk: A Multicenter Study in Italy and Spain

Author

Jordi Mayneris-Perxachs, Maria Francesca Russo, Rafel Ramos, Ana de Hollanda, Arola Armengou Arxé, Matteo Rottoli, María Arnoriaga-Rodríguez, Marc Comas-Cufí, Michele Bartoletti, Ornella Verrastro, Carlota Gudiol, Ester Fages, Marga Giménez, Ariadna de Genover Gil, Paolo Bernante, Francisco Tinahones, Jordi Carratalà, Uberto Pagotto, Ildefonso Hernández-Aguado, Fernando Fernández-Aranda, Fernanda Meira, Antoni Castro Guardiola, Geltrude Mingrone, José Manuel Fernández-Real, Obesity-T2DM Covid19 Study Group, Mariona Reixach Fumaña, Susana Jimenez-Murcia, Mikel Eatxandi, Alexander Rombauts, Gabriela Abelenda-Alonso, Caterina Guidone, Danila Anello, Giulia Giannetti, Emilio Ortega, Ignacio Conget, Clara Viñals, Carmen Hernández-Aguado, Josep-Maria Sirvent, Ramon Orriols, Mercé Fernández-Balsells, and Wifredo Ricart

Subjects
COVID-19, hemoglobin, hyperglycemia, obesity, epidemiology, mortality, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundHyperglycemia and obesity are associated with a worse prognosis in subjects with COVID-19 independently. Their interaction as well as the potential modulating effects of additional confounding factors is poorly known. Therefore, we aimed to identify and evaluate confounding factors affecting the prognostic value of obesity and hyperglycemia in relation to mortality and admission to the intensive care unit (ICU) due to COVID-19.MethodsConsecutive patients admitted in two Hospitals from Italy (Bologna and Rome) and three from Spain (Barcelona and Girona) as well as subjects from Primary Health Care centers. Mortality from COVID-19 and risk for ICU admission were evaluated using logistic regression analyses and machine learning (ML) algorithms.ResultsAs expected, among 3,065 consecutive patients, both obesity and hyperglycemia were independent predictors of ICU admission. A ML variable selection strategy confirmed these results and identified hyperglycemia, blood hemoglobin and serum bilirubin associated with increased mortality risk. In subjects with blood hemoglobin levels above the median, hyperglycemic and morbidly obese subjects had increased mortality risk than normoglycemic individuals or non-obese subjects. However, no differences were observed among individuals with hemoglobin levels below the median. This was particularly evident in men: those with severe hyperglycemia and hemoglobin concentrations above the median had 30 times increased mortality risk compared with men without hyperglycemia. Importantly, the protective effect of female sex was lost in subjects with increased hemoglobin levels.ConclusionsBlood hemoglobin substantially modulates the influence of hyperglycemia on increased mortality risk in patients with COVID-19. Monitoring hemoglobin concentrations seem of utmost importance in the clinical settings to help clinicians in the identification of patients at increased death risk.

Published
2021
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12. Impact of comprehensive molecular testing to reduce antibiotic use in community-acquired pneumonia (RADICAP): a randomised, controlled, phase IV clinical trial protocol

Author

Carlota Gudiol, Cristian Tebe, Jordi Carratalà, Gabriela Abelenda-Alonso, Alexander Rombauts, Yolanda Meije, Mercedes Clemente, Lucía Ortega, Carmen Ardanuy, Jordi Niubó, Ariadna Padullés, and Sebastian Videla

Subjects
Medicine
Abstract

Introduction Community-acquired pneumonia (CAP) continues to be a major health problem worldwide and is one of the main reasons for prescribing antibiotics. However, the causative agent is often not identified, resulting in antibiotic overtreatment, which is a key driver of antimicrobial resistance and adverse events. We aim to test the hypothesis that comprehensive molecular testing, compared with routine microbiological testing, would be effective in reducing antibiotic use in patients with CAP.Methods and analysis We will perform a randomised, controlled, open-label clinical trial with two parallel groups (1:1) at two tertiary hospitals between 2020 and 2022. Non-severely immunosuppressed adults hospitalised for CAP will be considered eligible. Patients will be randomly assigned to receive either the experimental diagnosis (comprehensive molecular testing plus routine microbiological testing) or standard diagnosis (only microbiological routine testing). The primary endpoint will be antibiotic consumption measured as days of antibiotic therapy per 1000 patient-days. Secondary endpoints will be de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, days to reaching an aetiological diagnosis, antibiotic-related side effects, length of stay, days to clinical stability, intensive care unit admission, days of mechanical ventilation, hospital readmission up to 30 days after randomisation and death from any cause by 48 hours and 30 days after randomisation. We will need to include 440 subjects to be able to reject the null hypothesis that both groups have equal days of antibiotic therapy per 1000 patient-days with a probability >0.8.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge Hospital (AC028/19) and from the Spanish Medicines and Medical Devices Agency, and it is valid for all participating centres under existing Spanish legislation. Results will be presented at international meetings and will be made available to patients, their caregivers and funders.Trial registration number ClinicalTrials: NCT04158492. EudraCT: 2018-004880-29.

Published
2020
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13. Effect of positive microbiological testing on antibiotic de-escalation and outcomes in community-acquired pneumonia: a propensity score analysis

Author

Gabriela Abelenda-Alonso, Alexander Rombauts, Carlota Gudiol, Esther García-Lerma, Natalia Pallarés, Carmen Ardanuy, Laura Calatayud, Jordi Niubó, Cristian Tebé, and Jordi Carratalà

Subjects
Adult, Microbiology (medical), Microbiologia, Pneumònia, Pneumonia, General Medicine, Microbiology, Anti-Bacterial Agents, Community-Acquired Infections, Antibacterial agents, Infectious Diseases, Anti-Infective Agents, Humans, Medicaments antibacterians, Propensity Score, Retrospective Studies
Abstract

Objectives: The usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP. Methods: A retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model. Results: Of 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96-3.41) and clinical stability at day 3 (AOR 1.87; 1.45-2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14-1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53-1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35-1.14)). Discussion: Antimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes.

Published
2022
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14. Characteristics and Outcomes by Ceiling of Care of Subjects Hospitalized with COVID-19 During Four Waves of the Pandemic in a Metropolitan Area: A Multicenter Cohort Study

Author

Natàlia, Pallarès, Cristian, Tebé, Gabriela, Abelenda-Alonso, Alexander, Rombauts, Isabel, Oriol, Antonella F, Simonetti, Alejandro, Rodríguez-Molinero, Elisenda, Izquierdo, Vicens, Díaz-Brito, Gemma, Molist, Guadalupe, Gómez Melis, Jordi, Carratalà, Sebastián, Videla, and Xavier, Piulachs

Abstract

The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia.Observational study conducted during the first (March-April 2020), second (October-November 2020), third (January-February 2021), and fourth wave (July-August 2021) of COVID-19 in five centers of Catalonia. All subjects were adults ( 18 years old) hospitalized with a proven SARS-CoV-2 infection and with therapeutic ceiling of care assessed by the attending physician at hospital admission.A total of 5813 subjects were analyzed. Subjects with a ceiling of care were mainly older (difference in median age of 20 years), with more comorbidities (Charlson index 3 points higher) and with fewer clinical signs at baseline than patients without a ceiling of care. Some features of their clinical profiles changed among waves. There were differences in treatments received during hospital admission across waves, but not between subjects with and without a ceiling of care. Subjects with a ceiling of care had a death incidence more than four times the death incidence of subjects a without a ceiling of care (risk ratio (RR) ranging from 3.5 in the first wave to almost 6 in the third and fourth). Incidence of severe pneumonia and complications for subjects with a ceiling of care was around 1.5 times the incidence in subjects without a ceiling of care.Analysis of hospitalized subjects with SARS-CoV-2 infection should be stratified according to therapeutic ceiling of care to avoid bias and outcome misestimation.

Published
2022

15. Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicenter study (BACTCOVID)

Author

Lluïsa Guillem, Alejandro Rodríguez-Molinero, Ariadna Padullés, Carlota Gudiol, Alexander Rombauts, M Mar Ras, Antonella F. Simonetti, Natalia Pallares, Elisenda Izquierdo, Alba Bergas, Gabriela Abelenda-Alonso, Alejandro Blanco-Arevalo, Ana Coloma, Jordi Carratalà, Cristian Tebé, Montserrat Sanmartí, Isabel Oriol, Inmaculada Grau, Vicens Diaz-Brito, Sebastián Videla, and Claudia Alvarez-Pouso

Subjects
Microbiology (medical), Adult, medicine.medical_specialty, Bacteremia, SARS-CoV-2 pneumonia, Immunomodulation, chemistry.chemical_compound, Tocilizumab, Risk Factors, Internal medicine, Hospital-acquired infection, medicine, Humans, Prospective Studies, Prospective cohort study, First episode, Cross Infection, business.industry, Hazard ratio, COVID-19, General Medicine, medicine.disease, bacterial infections and mycoses, Hospitals, COVID-19 Drug Treatment, Pneumonia, Infectious Diseases, chemistry, Spain, Case-Control Studies, Cohort, Original Article, business, human activities
Abstract

Objectives The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. Methods We performed a severity matched case-control study (1:1 ratio) nested in a large multicenter prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex, and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. Results Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9 - 20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59 [1.65 – 4.07], Graphical abstract Image 1

Published
2021

16. Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Author

Jesús Rodríguez-Baño, Jerónimo Pachón, Jordi Carratalà, Pablo Ryan, Inmaculada Jarrín, María Yllescas, José Ramón Arribas, Juan Berenguer, Esther Aznar Muñoz, Pedro Gil Divasson, Patricia González Muñiz, Clara Muñoz Aguirre, Marta Díaz Menéndez, Fernando de la Calle Prieto, Marta Arsuaga Vicente, Elena Trigo Esteban, Ignacio Pérez Valero, Rosa de Miguel Buckley, Julen Cadiñaños Loidi, Beatriz Diaz Pollan, Luz Martín Carbonero, Juan Carlos Ramos Ramos, Belén Loeches Yagüe, Rocío Montejano Sánchez, Juan González García, Julio García Rodríguez, Margarita Ramírez, Isabel Gutiérrez, Francisco Tejerina, Teresa Aldámiz-Echevarría, Cristina Díez, Chiara Fanciulli, Leire Pérez-Latorre, Blanca Pinilla, Juan Carlos López, Ana Such Diaz, Elena Álvaro Alonso, Juan Torres Macho, Guillermo Cuevas Tascon, Eva Jiménez González de Buitrago, Fátima Brañas Baztán, Jorge Valencia de la Rosa, Mario Pérez Butragueño, Inés Fernández Jiménez, Gemma Muñiz Nicolás, Antonia Sepúlveda Berrocal, Alberto Gato Díez, María Pilar Toledano Sierra, María Paz García Butenegro, Ana Isabel Peláez Ballesta, Elena Morcillo Rodríguez, Isidoro Fernández Romero, Cristina Peláez Ballesta, María Isabel Guirado Torrecillas, Josune Goikoetxea Agirre, Elena Bereciartua Bastarrica, Laura Guio Carrión, Regino Rodríguez Álvarez, Marta Ibarrola Hierro, Isabel A. Pérez Hernández, Inés Pérez Zapata, Sergio Román Soto, Mohamed Kallouchi, Juan Ramón Domínguez Vicent, Rafae Silvariño Fernández, Jon Ugalde Espiñeira, Ainhoa Sanjuan López, Silvia García Martínez, Mikel Temprano Gogenola, Víctor Asensi, Silvia Suárez, Lucia Suárez, Carmen Yllera, María Rivas-Carmenado, Alberto Romero-Palacios, Jesús Ruiz Aragón, Patricia Jiménez Aguilar, Ma Luisa Fernández Ávila, Rosario Castilla Ortiz, Vanesa Alende Castro, Cristina Pérez García, Marta Fernández Morales, María Lorena María Valle Feijoo Begoña Rodríguez Ferreira, Joan Gómez-Junyent, Judit Villar-García, Inmaculada López-Montesinos, Itziar Arrieta-Aldea, Abora Rial-Villavecchia, Elisa García Vázquez, Aychel Elena Roura Piloto, Encarnación Moral Escudero, Alicia Hernández Torres, Helena Albendín Iglesias, David Vinuesa García, Clara Martínez Montes, Francisco Javier De la Hera Fernández, Francisco Anguita Santos, Andrés Ruiz Sancho, Vicens Díaz de Brito Fernández, Montserrat Sanmarti Vilamala, Sergio España Cueto, Daniel Molina Morant, Araceli González-Cuevas, Joel Elías Chara Cervantes, Guillem Policarpo Torres, Meritxell Ortega Montoliu, Mònica Angerri Nadal, Ariadna De Genover Gil, Eleni Patera, Rita Godoy Lorenzo, Evangelia Anna María Zioga, Virginia Isern Fernández, Carlos Enrique Sabbagh Fajardo, Ana Ferrer Ribera, Carlos Bea Serrano, Rosa Oltra Sempere, Sara Vela Bernal, Paloma Albiol Viñals, Miguel Pedromingo Kus, María Ángeles Garcinuño, Silvana Fiorante, Sergio Pérez Pinto, Alexandra de la Vega, María Carmen Fariñas Álvarez, Claudia González Rico, Francisco Arnaiz de las Revillas, Teresa Giménez, Jorge Calvo, Yolanda Meije Castillo, Alejandra Duarte Borges, Júlia Pareja Coca, Mercedes Clemente Presas, Xavier Sanz Salvador, Ma Teresa Pérez Rodríguez, Adrián Sousa, Alexandre Pérez González, Rebeca Longueira, Alejandro Araujo, Blanca Alonso Martínez, Laura García Escudero, Sara Lidia Kamel Rey, David Roa Alonso, Juan Pablo Avilés Parra, Iván Pelegrín Senent, Rosana Rouco Esteves Marques, Laia Raich Montiu, Jessica Souto Higueras, Manuel Alejandro Gálvez Bobadilla, Jorge Parra Ruiz, Violeta Ramos Sesma, Sara Velasco Fuentes, Laura García Pereña, Alfonso Lluna Carrascosa, Sergio Gilaberte Reyzábal, Mónica Liébana Gómez, Juan Salillas Hernando, Alberto Serrano Martínez, Miguel Torralba González de Suso, Patricia Martínez Martín, Isabel Rábago Lorite, Patricia González-Ruano Pérez, Beatriz Pérez-Monte Mínguez, Ángeles García Flores, Pere Comas Casanova, Andrea Martín Plata, Sergio Manuel Santana Báez, Oscar Sanz Peláez, Karim Mohamed Ramírez, José María Robaina Bordón, Helem Haydeé Vílchez Rueda, Melchor Riera Jaume, Gemma Mut Ramon, Meritxell Gavalda Manso, Lluis Planas Bibiloni, Laura Castelo Corral, Lucía Ramos Merino, Efrén Sánchez Vidal, María Rodríguez Mayo, Enrique Míguez Rey, José M. García de Lomas Guerrero, Javier De la Torre Lima, Ana Correa Ruiz, Fernando Fernández Sánchez, Nicolás Jiménez-García, José Luis Sierra-Monzón, Borja Gracia-Tello, María Hernández-Bonaga, Galadriel Pellejero, Marta Asín-Corrochano, Lucia Boix Palop, Esther Calbo, Cristina Badía, Beatriz Dietl, Gómez Lucía, Ángel Domínguez-Castellano, María José Ríos-Villegas, María D. del Toro, Zaira R. Palacios Baena, Elena Salamanca-Rivera, Elena Marín, Virginia Almadana, Salvador Pérez-Galera, Luisa González-Iglesias, Gabriela Abelenda-Alonso, Claudia Álvarez-Pouso, Francesc Escrihuela, Carlota Gudiol, Laia Lorenzo-Esteller, Jordi Niubó, Daniel Podzamczer, Miquel Pujol, Alexander Rombauts, Miguel Salvert Lletí, Ricardo Gil Sánchez, Marta Jiménez Escrig, Laura Parra Gómez, Mariona Tasias Pitarch, Marta Navarro Vilasaró, María Luisa Machado Sicilia, Aina Gomila Grange, Sonia Calzado Isbert, Nerea Carrasco Antón, Elizabet Petkova-Saiz, Alfonso Cabello Úbeda, Miguel Górgolas Hernández-Mora, Olga Sánchez-Pernaute, Carlos Dueñas Gutiérrez, Javier Martin Guerra, José Javier Castrodeza Sanz, Virginia Fernández Espinilla, Laura Rodríguez Fernández, Juan González-Moreno, Aroa Villoslada Gelabert, María Antonia Ribot Sanso, María Victoria Fernández-Baca, Almudena Hernández Milian, Miguel Ángel Morán Rodríguez, Zuriñe Ortiz de Zárate Ibarra, José Joaquin Portu Zapirain, Ester Saez de Adana Arroniz, Juan Carlos Gainzarain Arana, Olga Meca Birlanga, Ma Jesús del Amor Espín, Montserrat Viqueira González, Josefina García García, Onofre Martínez Madrid, Enrique Bernal Morell, Antonia Alcaraz, Ángeles Muñoz, Ignacio Pina, Vicente de la Rosa, Tamara Caínzos Romero, Sabela Sánchez Trigo, Ana Isabel Mariño Callejo, Hortensia Álvarez Díaz, Nieves Valcarce Pardeiro, Adriana Sánchez Serrano, Diana Piñar Cabezos, Eva Pilar García Villalba, Carmen Aguayo Jiménez, María Ruíz Campuzano, Virginia Naranjo Velasco, Marta Santos Peña, Juan Mora Delgado, Israel Sevilla Moreno, Cristina Lojo Cruz, Xabier Kortajarena Urkola, José Antonio Iribarren Loyarte, María Jesús Bustinduy Odriozola, Maialen Ibarguren Pinilla, Ignacio Álvarez Rodríguez, Francisco Javier Martínez Marcos, Francisco Javier Rodríguez Gómez, Isabel Asschert Agüero, Francisco Muñoz Beamud, Antonio José Ruiz Reina, Jara Llenas-García, Inmaculada González-Cuello, Elena Hellín-Valiente, Esther Martínez Birlanga, José Manuel Tafalla Torres, Jorge Calderón Parra, Gabriela Escudero López, Isabel Gutiérrez Martín, Ane Andrés Eisenhofer, Sonia García Prieto, Raquel Álvarez Franco, Daniel Roger Zapata, Blanca Martínez Cifre, Elena Aranda Rife, Irene Martín Rubio, André Barbosa Ventura, Javier Garrido, Concepción Gonzalo, Iván Piñero, Nieves de la Cruz Felipe, Eva Talavera García, Marta Lamata Subero, Paula Mendoza Roy, María Soledad García de Carlos, Justo Lajusticia Aisa, Lorea Arteche Eguizabal, Ainhoa Urrutia Losada, Saioa Domingo Echaburu, Pedro Ángel Cuadros Tito, Gurutz Orbe Narváez, Ma del Carmen Liébana Martos, Carolina Roldán Fontana, Carmen Herrero Rodríguez, Gaspar Duro Ruiz, Santiago Pérez Parra, Arantzazu Mera Fidalgo, Miquel Hortos Alsina, Ana Alberich Conesa, Lourdes Bladé Vidal, Nicolás Merchante Gutiérrez, Eva León Jiménez, Reinaldo Espíndola Gómez, María Erostarbe Gallardo, Pedro Martínez Pérez-Crespo, José Miguel Cisneros, Manuela Aguilar-Guisado, Teresa Aldabó, Claudio Bueno, Elisa Cordero-Matía, Ana Escoresca, Carmen Infante, Martín Guillermo, Sonsoles Salto, Francesca Gioia, Pilar Vizcarra, Jesús Fortún Abete, Pilar Martín Dávila, Santiago Moreno Guillén, José A. Oteo Revuelta, Concepción García-García, Paula Santibañez Sáenz, Cristina Cervera Acedo, José M. Azcona Gutiérrez, José María Reguera Iglesias, Antonio Plata Ciezar, Lucia Valiente de Santis, Beatriz Sobrino Diaz, Juan Diego Ruiz Mesa, Ministerio de Ciencia e Innovación, Fundación SEIMC/GeSIDA, Instituto de Salud Carlos III - ISCIII, European Regional Development Fund (ERDF/FEDER), Red Española de Investigación en SIDA, Red Española de Investigación en Patología Infecciosa, UAM. Departamento de Medicina, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, Universidad de Cantabria, SAM-COVID Study Group, [Rodríguez-Baño,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Departamento de Medicina, Universidad de Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Pachón,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Carratalà,J] Servei de Malalties Infeccioses, Hospital Universitari de Bellvitge, Barcelona, Spain. [Carratalà,J] Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Carratalà,J] Universitat de Barcelona, Barcelona, Spain. [Ryan,P] Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain. [Jarrín,I] Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain. [Yllescas,M] Fundación SEIMC/GeSIDA, Madrid, Spain. [Arribas,JR] Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. [Arribas,JR] Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain. [Berenguer,J] Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Berenguer,J] Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain., Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Red de Investigación Cooperativa en Investigación en Sida (España), Red de Investigación Cooperativa en Investigación en Patología Infecciosa (España), Gilead Sciences, ViiV Healthcare, AbbVie Pharmaceuticals, Merck & Co, Janssen Biotech, Teva Pharmaceutical Industries, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Universidad de Sevilla. Departamento de Medicina, Instituto Carlos III (España), and Unión Europea

Subjects
0301 basic medicine, Male, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Organisms::Viruses::RNA Viruses::Nidovirales::Coronaviridae [Medical Subject Headings], Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hospital Mortality, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Vital Statistics::Mortality [Medical Subject Headings], Adrenocortical hormones, Hazard ratio, General Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Intubation::Intubation, Intratracheal [Medical Subject Headings], Middle Aged, Tocilizumab, Hospitalization, Infectious Diseases, Treatment Outcome, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections [Medical Subject Headings], Drug Therapy, Combination, Female, Cohort study, Microbiology (medical), medicine.medical_specialty, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections::Severe Acute Respiratory Syndrome [Medical Subject Headings], Combination therapy, Medicina, Hyperinflammatory state, 030106 microbiology, Estudios de cohortes, Antibodies, Monoclonal, Humanized, Article, 03 medical and health sciences, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Intubation, Intratracheal, Mortalitat, Humans, Corticosteroids, Mortality, Corticoesteroides, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Aged, Proportional Hazards Models, Retrospective Studies, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Inflammation, business.industry, SARS-CoV-2, COVID-19, Odds ratio, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones [Medical Subject Headings], Corticosteroides, COVID-19 Drug Treatment, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Propensity Score [Medical Subject Headings], chemistry, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Propensity score matching, Mortalidad, Monoclonal antibodies, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Anticossos monoclonals
Abstract

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

Published
2021

17. Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score

Author

Juan Salillas, Miguel Fernández Huerta, Patricio González-Pizarro, Francisco Javier Membrillo, Raul Galera, Jesús Rodríguez-Baño, Lydia Galvez, Juan Cuadros-González, Aina Gabarrell-Pascuet, Jorge Diaz-Garzon, INMA JARRIN, Claudia González-Rico, Alicia Rico Nieto, Cristina Cervera, Carlos Bea Serrano, Alberto Ouro Villasante, Guillermo Ruiz-Carrascoso, Beatriz Díaz-Pollán, María del mar Arcos Rueda, Julio Garcia-Rodriguez, BELEN GUTIÉRREZ-GUTIÉRREZ, MARCO ANTONIO SEMPERE ALCOCER, Cristina Verdú Sánchez, Lucía Hernández-Rivas, Guillermo Cuervo, Alejandro Smithson, Miguel Torralba, Iván Bloise, Alexander Rombauts, Carlos Toro, Lucio Jesus García-Fraile Fraile, Alejandro García-Ruiz de Morales, Cecilia Tortajada, KAPIL LAXMAN NANWANI NANWANI, Lorena De la Mora Cañizo, Laia Lorenzo-Esteller, Jorge Álvarez Troncoso, Cristina Roca Oporto, Alejandro Martin-Quiros, José A. Oteo, Eduardo Malmierca Corral, Stefan Stewart, Jerónimo Pachón, Almudena Gutiérrez-Arroyo, Moreno-Cuerda Victor, Carlos Carpio, Emilio Cendejas-Bueno, Pilar Fernandez-Calle, Antonio Javier Carcas Sansuán, Alexy Inciarte, Pablo Ryan, Luis Puente-Maestu, Jesús Troya García, Francisco de Asís Alcántara Nicolás, Gabriela Abelenda-Alonso, Natividad Benito, Daniel Prieto Arribas, Jesus Mingorance, Jose L Del Pozo, Jordi Carratala, Cristina Marcelo, Marta Ruiz-Algueró, Sarah CARO BRAGADO, Juan Berenguer, Vicens Diaz-Brito, Víctor Hontañón Antoñana, Julen Cadiñanos, Jose Arribas, María Jesús Jaras Hernández, Henar Calvo Sánchez, Elisa Cordero, Instituto de Salud Carlos III, Fundación Seimc-Gesida, Plan Nacional de I+D+i (España), Ministerio de Ciencia y Universidades (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Red de Investigación Cooperativa en Investigación en Sida (España), Red de Investigación Cooperativa en Investigación en Patología Infecciosa (España), Fundación SEIMC-GESIDA, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Red Española de Investigación en SIDA, Red Española de Investigación en Patología Infecciosa, Universidad de Cantabria, UAM. Departamento de Farmacología, and UAM. Departamento de Medicina

Subjects
Male, Neutrophils, Respiratory Infection, 030204 cardiovascular system & hematology, Logistic regression, 0302 clinical medicine, Diagnòstic, Risk Factors, Respiratory infection, Diagnosis, Epidemiology, 030212 general & internal medicine, Hospital Mortality, Aged, 80 and over, Prediction theory, Age Factors, clinical epidemiology, Middle Aged, Tool, Emergency medicine, Female, Glomerular Filtration Rate, Pulmonary and Respiratory Medicine, Adult, Prognostic variable, medicine.medical_specialty, Medicina, Renal function, Diagnosis tripod, 03 medical and health sciences, Sex Factors, emergency medicine, Internal medicine, medicine, pneumonia, Humans, Derivation, Lymphocyte Count, Aged, Inpatients, Receiver operating characteristic, business.industry, SARS-CoV-2, Clinical epidemiology, COVID-19, Pneumonia, medicine.disease, Individual prognosis, critical care, Oxygen, Critical care, Logistic Models, Dyspnea, ROC Curve, Teoria de la predicció, Viral infection, viral infection, business, Kidney disease
Abstract

COVID-19@Spain and COVID@HULP Study., [Objective] To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms., [Design] Multivariable prognostic prediction model., [Setting] 127 Spanish hospitals., [Participants] Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively., [Interventions] Prognostic variables were identified using multivariable logistic regression., [Main outcome measures] 30-day mortality., [Results] Patients’ characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806–0.837) in the DC and 0.845 (0.819–0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0–2 points (0%–2.1%), moderate with 3–5 (4.7%–6.3%), high with 6–8 (10.6%–19.5%) and very high with 9–30 (27.7%–100%)., [Conclusions] A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19., This work was supported by Fundación SEIMC/GeSIDA. The funders had no role in study design, data collection, data interpretation or writing of the manuscript. JB, JRB, IJ, JC, JP and JRA received funding for research from Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, cofinanced by the European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020. Spanish AIDS Research Network (RIS) (RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16CIII/0002/0006 (IJ)). Spanish Network for Research in Infectious Diseases (REIPI) (RD16/0016/0001 (JRB), RD16/0016/0005 (JC) and RD16/0016/0009 (JP)).

Published
2021

18. Immunological imprinting of the antibody response in COVID-19 patients

Author

Daniel Stadlbauer, Sadaf Aslam, Kaijun Jiang, Fatima Amanat, Jordi Carratalà, Gabriela Abelenda-Alonso, Alexander Rombauts, Alba Escalera, Adolfo García-Sastre, Teresa Aydillo, and Florian Krammer

Subjects
0301 basic medicine, Male, Coronavirus disease 2019 (COVID-19), viruses, Science, Immunology, General Physics and Astronomy, Cross Reactions, Antibodies, Viral, Immunological memory, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Pandemic, Humans, 030212 general & internal medicine, Immunologia, Imprinting (psychology), skin and connective tissue diseases, Aged, Multidisciplinary, biology, SARS-CoV-2, fungi, virus diseases, COVID-19, General Chemistry, Antimicrobial responses, respiratory tract diseases, body regions, Humoral immunity, 030104 developmental biology, Antibody response, Viral infection, Antibody Formation, Spike Glycoprotein, Coronavirus, biology.protein, Female, Antibody
Abstract

In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection., In addition to SARS-CoV-2, other coronaviruses also infect human, but whether consecutive infections cross-modulate the induced immune response is still unclear. Here the authors show that SARS-CoV-2 infection boosts pre-existing responses to other coronaviruses, yet such back-boosting hampers the induction of specific antibodies against SARS-CoV-2.

Published
2021

19. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study

Author

Jaime Fernández-Bujarrabal Villoslada, Beatriz Dietl Gómez-Luengo, Daniel Ortiz-Sánchez, José Ramón Blanco Ramos, Bartolomé Gómez-Arroyo, Martín Sebastián Ruiz Grinspan, Ester Sáez de Adana Arróniz, Daniel Daniel López, Judit Villar-García, Begoña De Dios García, Josefina García García, Nuria Rabella García, Ana Rodríguez-Revillas, Lydia Martín González, Mercedes San Franco, Elena Martinez Robles, Teresa González Alegre, Elena Morcillo Rodríguez, Oriol Gasch Blasi, Laura Prieto Pérez, Isabel Jiménez Martínez, Elena Isaba Ares, Ricardo Deza-Palacios, Helena Mendez del Sol, Melchor Riera Jaume, Mercedes Rodriguez-Gutiérrez, Daniel Podzamczer, Mikel Urroz, Luis Ramos Ruperto, María Paniagua, Sergio Alcolea-Batres, Mar Masiá Canuto, Rubén Soriano-Arroyo, Paloma Merino Amador, Berta Antón-Huguet, Gabriela Alcaraz, Pablo Ryan, Carlos Franco, Leyre Díez-Porres, Juan Carlos Figueiras, Sara Lidia Kamal, Mónica Hernández, Lorena Barrera-López, Germán Ramírez-Olivencia, Kapil Laxman Nanwani Nanwani, Alberto Oreja, Montserrat Laguno, José Javier Castrodeza Sanz, Belén Loeches Yagüe, Maria Vargas, Luis Eduardo López-Cortés, Isabel Gutiérrez, Sara Vela Berna, P. Martín, Miguel Pedromingo Kus, Jesús Sanz Sanz, Mº Antonia Sepúlveda Berrocal, Carmen Yera Bergua, Juan Cuadros González, Julen Cadiñanos Loidi, Josefa Serralta Buades, María Concepción Prados Sánchez, Francesca Gioia, Iris Pedrola Gorrea, Francisco Arnaiz de las Revillas, Xabier Kortajarena Urkola, Laia Lorenzo-Esteller, Ruth Bravo-Lizcano, Angel Iniesta, Sofía González-García, Belén Martínez López, Agustín Rojas-Vieyra, Concepción García García, Raquel Cavallé-Pulla, Lucía Gómez García, Alicia Herrero, Carlos Jesús Dueñas Gutiérrez, Loreto Vidaur Tello, Carmen Fernández-Capitán, Victoria Lo-Iacono García, Cecilia Gómez-Domínguez, Adalgisa Falcone, María José Ruiz Rodríguez, Arancha Castellano, Miquel Hortos Alsina, María Concepción Nuñez, María Luisa Fernández Vidal, Jésica Abadia Otero, Natalia Moya-González, Albert Sabater Gil, Pedro de la Oliva, Ylenia María Conde-Alonso, Laura Castelo Corral, José Mº García de Lomas Guerrero, Verónica Pérez-Blanco, Isabel San Juan, Martina Archinà, Júlia Sellarés, Juan Carlos Ramos, Cintia María Martínez Mateu, Belén Fernández-Puntero, Andrea Torrecillas-Mainez, Luis Falgueras López, Carlos Carpio-Segura, María Gandullo-Moro, Francisco Abellán Martínez, Cristina Díez, Pilar Martín Dávila, Silvia Gómez-Zorrilla, María Pilar García García, Renzo Tejada-Sorados, María Dolores del Toro, E. Álvarez-Rojas, Gema Muñiz, Lucía Cajuela, María Novella Mena, Estel Pons Viñas, Andrea Pérez Rodríguez, Benito Almirante, Mónica Gozalo, Patricia Girón De Velasco-Sada, Camilo Sanz Zamudio, Ángeles García Flores, Joaquín López-Contreras González, Blanca Fabre-Estremera, Pelayo Fernández Cidón, María Martínez-Redondo, Paula Alejandra Hernández-Liebo, Juan Herrero, Marta Duque-Alcorta, María Teresa García Morales, Concepción Amador Prous, Alex Soriano, Raquel Hernando Nieto, Raquel Álvarez Franco, Alfonso Cabello Úbeda, Luis Force Sanmartín, Laura Mao Martín, Daniel Prieto-Arribas, Mario Pérez-Butragueño, Pere Domingo Pedrol, Henar Serrano-Martín, Mónica Zubimendi, M. Rodríguez-Rubio, David Pujol-Pocull, Manuel García-Gutiérrez, Carlos Manrique de Lara, Lucy Abella Vázquez, Marta Navarro Vilasaró, Carlota Cascajares-Sanz, Berta Torres, Daniel Ceniza-Pena, Isidro Moreno Gómez-Limón, María Rodríguez Mahía, Alí Martakoush, Antonio Buño-Soto, Patricia Serrano de la Fuente, Claudia González Rico, Teresa Pedraz, Conchita Pérez-Jorge Peremarch, Elena Trigo Esteban, Rosana Rouco Esteves Marques, Juan Mora Delgado, Inés Pérez Zapata, Sandra Pérez-Recio, María Ángeles Domínguez, Manuel Cervantes García, Francisco Reinoso-Lozano, M. Martí De Gracia, Carmina Oltra, Beatriz Pérez-Monte Mínguez, Guillermina Bejarano-Redondo, Sara Heili Frades, María Paz García Butenegro, Miguel Torralba González de Suso, Elena Álvaro-Alonso, Víctor J Moreno Cuerda, Gonzalo Garzón, Marcelo Daltro-Lage, Alberto Serrano Martínez, José María Aguado, Mar Mosquera, Ruth Figueroa Cerón, Juan Carlos Martin Gutiérrez, Javier Oliver Ortega, Esteban Martínez, Cristina Gómez-Ayerbe, Nerea Carrasco Antón, María Carmen Fariñas Álvarez, José Antonio Ruiz, Justo Menéndez, Lucía Díaz, José L. Casado, Pilar Vizcarra, Javier Veganzones, Miguel Ángel Moran Rodríguez, Mercedes López-Martinez, Emilio Letang, Paloma Romero Gallego-Acho, Julia Vasquez-Manau, Alexander Rombauts, Marta Robledo del Prado, Luis Puente, Beatriz Alvarez, Juan Emilio Losa García, José Tomas Algado Rabasa, Rafael Torres Perea, Angélica Rivera-Núñez, Esther Expósito Palomo, Antonio J. Carcas, Lucía Platero-Dueñas, Irene Martín Rubio, Miguel Salavert Lletí, Claudia García-Vaz, Antonio Martínez-Verdasco, Jorge Díaz-Garzón, Javier Nieto Arana, Fernando Cadenas-Gota, Richard Rojas, Abelardo García de Lorenzo, Juan Carlos López, Pedro Luis Martinez Hernández, Manuela de Pablos-Gómez, Pablo Alonso, Enrique Seco, María García-López, Lorena López-Corcuer, Celia Blasco-Andres, Delia Romera-Cano, José M. Azcona Gutiérrez, Almudena Gutiérrez-Arroyo, Paula Mendoza Roy, Ignacio De los Santos Gil, Miguel Angel Sánchez-Castellano, Sara Medrano Pardo, Mikel del Álamo Martínez de Lagos, Rocío Martínez Avilés, Elisabet Martínez-Cerón, José Manuel Vázquez Comendador, Marta Virgós-Varela, Alejandra Álvarez Brandt, Carmen Herrero Rodríguez, Jorge Martínez Jordán, Antonio Rezusta López, Marta Vizcaíno Callejón, Manuela Simon-Velasco, Jorge Ignacio Alonso-Eiras, Elisa García Vázquez, Mercè Gurguí Ferrer, Mónica González Bardanca, Nataly Cancelliere-Fernández, José Luis Díaz de Tuesta del Arco, María Larrosa, Alejandro García García, Carmen Román-Hernández, Elena Calvin-García, José Sanz Moreno, Miguel Silvestre-Niño, Nieves Valcarce Pardeiro, Maria Teresa Corcuera-Pindado, Enrique Monteoliva, Aina Gabarrell Pascuet, Elena María Aranda Rife, Aina Gomila Grange, Alba Alastrué Violeta, Daniel Roger Zapata, Jaime Montserrat, Eduardo Malmierca Corral, Marco Palma, Blanca Martínez Cifre, Gema Domínguez de Pablos, Emilio Cuesta, Eva Perales, Silvia Hernáez Crespo, Juan Torres-Macho, Adrián Sánchez Montalvá, Rocío Montejano Sánchez, Eva Van den Eynde Otero, Silvia Castañeda Espinosa, Virginia Pérez Doñate, Adriana Hernández Belmonte, Laura Iglesias Llorente, María Sanz de Pedro, Juan Espinosa Pereiro, Lubna Dani Ben-Abdellah, Raquel Barrós González, Iván Piñero, Araceli López-Tofiño, Ana Such-Diaz, Karim Mohamed Ramírez, Pilar Toledano Sierra, Rebeca Izquierdo, Guillermo Cuevas, Andrés Felipe Cardona Arias, Ileana Gabriela-Tomoiu, David Vinuesa García, Ander González Sarria, Stephan Stuart, José María Fernández, Javier Torres-Cortés, Elisabet Delgado Sánchez, María Varela-Cerdeira, Gemma Bassani, Berta Román Bernal, Isabel García, Paula Betancort de la Torre, Yolanda Martínez-Abad, Beatriz Arizcun, Juan José Cabanillas-Martín, Guillermo Estrada Fernández, Oscar del Río Pérez, Inmaculada Martín Pérez, Andony García, Luis Gómez-Carrera, Alexander Agrifoglio, Alberto M. Borobia, Jordi Niubó, Vanessa Alende Castro, Lara Montes Andújar, Alexandra De la Vega, Efrén Sánchez Vidal, Isabel A. Pérez Hernández, Laura Frade-Pardo, Ana Josefa Tebar-Martinez, Silvia Álvarez Kaelis, Sara De la Fuente Moral, Luz Martin Carbonero, Juan Cantón De Seoane, María Dolores Montero-Vega, Juan Carlos Gainzarain Arana, Sergio España Cueto, Rocío Nuñez-Cabetas, María Sánchez-Martín, Constanza Muñoz Hornero, Ana Gómez-Zamora, Javier Díaz Luperena, Patricia González-Donapetry, José Miguel Cisneros, Lucía Hernández-Rivas, Patricia González Ruano, Andrea Espigares Correa, Rocío González-León, Nicolás García-Arenzana, Omar Cervera, Andrés Canut Blasco, Ana Isabel Cañabate, Mercedes Villarreal García-Lomas, Melania Íñigo Pestaña, Maria Álvarez de Castro, Ana Correa Ruiz, Belén Civantos, Lydia Pascual-García, Paula Villares Fernández, Mikel Rico-Briñas, María José Alcaide-Martín, Adoración Valiente, Victoria Arnalich-Montiel, Pilar Retamar, Jesús Mingorance, Eva María Romay Lema, Pablo Galindo-Ballesteros, M. Teresa Pérez-Rodríguez, Rosario Maria Torres Santos-Olmo, Inmaculada Pinilla, Elie Dahdouh, Beatriz Tejero-Soriano, Cristina Pizarro-Sanchez, Félix Gutiérrez Rodero, Luis Jara-Palomares, María Hernández-Gancedo, Cristina Chico Chumillas, Sergio Gilaberte Reyzábal, Manuel González-Viñolis, Ana Martínez Sapiña, Francisco Parras, Teresa Rubio Obanos, Iker Falces-Romero, Adriana Sánchez Serrano, Teresa Álvarez de Espejo Montiel, Jorge Valencia, Miquel Pujol, José Luis Velasco Garrido, Belén Calderón-Llopis, Álvaro Varela Plaza, Abel Caro, Juan José González-Garcia, Miguel Sampedro Núñez, María Fernández-Velilla, Emilio Cendejas-Bueno, María Cecilia Cánepa, José Luis Santiago Blanco, Alicia Rico-Nieto, Mónica Liébana Gómez, Sarah Caro Bragado, Susana Sánchez-Rico, José María Marimón Ortiz de Zárate, Paloma Dorao, Cristina Plaza-Moreno, Isabel Valbuena, Natividad Benito Hernández, Ginger Giorgiana Cabrera Tejada, Jordi Carratalà, Sara Fernández Rodríguez, Vicente Ferrer Díaz De Brito Fernández, Pilar Catalán, Pablo Mariscal-Aguilar, Germán Daroca-Bengoa, Rafael Fernandez, Raquel Casitas-Mateo, Ester Zamarrón de Lucas, Úrsula Quesada, Julio Yagüe, María Isabel Quijano Contreras, Trinidad Baselga-Puente, Lourdes Herrera Pacheco, Carlota Gudiol, Alazne Lartategi Iraurgi, Estefanía Martinez-Chavez, Silvia Valero Rovira, Alba Bergas, Zaida Ruiz de Azua, Teresa Prim, Cristina García-Quero, Pilar Hernández Machín, Rubén Gomez-Rioja, María Pavón-Masa, María de las Mercedes Valentín-Pastrana Aguilar, Ilduara Pintos Pascual, Lucía Brieba-Plata, María Jesús Domínguez Santalla, Francisco Javier Membrillo de Novales, Raúl Galera-Martínez, Ana Lérida Urteaga, Miguel Cervero, Alberto Mangas-Moro, José Hernández Quero, Teresa Sancho Bueso, María Angustias Quesada Simón, Luz Parra-Gordo, Sofía Díaz-Carrasco, Juan Carlos Abad Almendro, Andrés Javier Ruiz Fernández, Estíbaliz Molina Iturritza, Aurea Díez-Tascón, Yale Tung-Chen, Marta Rava, Carlos Villasante, Gabriel Gaspar Alonso-Vega, Clara Cabré-Verdiell Surribas, Esther Fraile Villarejo, Aida Gutiérrez García, Ana Robustillo-Rodela, Rafael Padrós Selma, Jesús Rodríguez-Baño, Frank Perdomo-García, Lydia de la Fuente Regaño, María del Mar Arenas-Miras, Cristina Rodríguez Roca, Blanca Montero-San Martín, Gema Crespo-Sánchez, Miguel Ramírez-Verdyguer, Alberto Diaz de Santiago, Marta Díaz Menéndez, María de la Luz Padilla Salazar, Silvia Arribas-Terradillos, Sadaf Zafar Iqubal-Mirza, Isabel Rábago Lorite, Belén Estébanez, Maite Ganchegui Aguirre, André Barbosa Ventura, Estefanía Fernandez-Cerezo, Maria Eulalia Valencia, Zaira R. Palacios-Baena, Beatriz Diaz Pollan, Lidia Martín, Sara Fabra-Cadenas, José Miguel Cantero-Escribano, Carmen Busca Arenzana, Emilia Guasch-Arévalo, Virginia Fernández Espinilla, Ainhoa Urrutia Losada, Oscar Noya González, Raquel Aranega, Alejandro Rodríguez Saenz de Urturi, María Jesús Jaras Hernandez, Charbel Maroun Eid, Marta Mora Rillo, Antonio Ramos Martínez, Meritxell Ortega Montoliu, Jose María Mostaza, Sonia García Calvo, Cristina Verdú, Celia Salamanca, Cristina Cervera Acedo, Mónica Martínez, Miren Urrestarazu Larrañag, Carmen Barroso Castro, Ivo Vives-Beltrán, Lorea Arteche Eguizabal, Ana Montero, Javier Balsa Vázquez, Amparo Perez-Garcia Morillón, Alejandra Pérez García, Isabel Pérez-Tamayo, Rafael Cantón Moreno, Antonio Marín-García, Inmaculada Jarrín, Núria Trullen, Ines Fernandez-Jimenez, Guillermo Ruiz-Carrascosa, Almudena Villa Martí, Jamil Cedeño, Marcos Díez Martínez, Carlos Lahoz, Lorena De la Mora, Javier Sánchez-Lora, Ana María Martínez-Virto, Irene Sanjosé Muñiz, Adrian Peña-Hidalgo, Cristina López Mestanza, Carola Gutiérrez, Ana Laila Qasem-Moreno, Irene Salvo García, Lucía Fernández de Orueta, Jorge Parra Ruiz, Sergio Pérez Pinto, Carlos García-Mochales Fortún, Esteban García de las Heras, Patricia González Muñiz, Mario Fernández-Ruiz, Anna Ferrer Santolaria, Olga Sánchez Pernaute, Julieta Latorre, Jesús Manzanares, Miguel Angel Martinez Gallego, Helena Notario, Ángel Rodríguez-Villodres, Eva Fernández-Bretón, Encarnación Moral Escudero, Mónica Sánchez-Santiuste, Carmen Martínez Cilleros, Ricardo Fernández Roblas, María Yllescas, Eva Soria-Alcaide, Marta Arsuaga Vicente, Marta Gómez-López, Regina Cabrera-Gamero, Natalia Carrasco Fons, Diana Piñar Cabezos, Begoña Sánchez-Sánchez, Francisca Garcia-Iglesias, Raquel Marín-Baselga, Alberto Arranz Caso, Virginia Guedez-López, Lucia Boix Palop, Íñigo Gredilla Zubiría, María Hidalgo-Sánchez, Laura López-Tappero Irazábal, José Ignacio Bernardino de la Serna, Javier Queiruga, Natalia Guadalupe Barrera-López, María López-Jodar, Jorge Calderón Parra, Diego Rodríguez-Álvarez, José Molina, María Luisa Montes, Beatriz Rodríguez-Alonso, Daniel Useros Brañas, Maria Gracia Liras-Hernández, Lucía Romero-Imaz, Nieves Jaén Sánchez, Marta Segovia-Amaro, Marta Vara, Maribel Zamora Cintas, Montaña Jiménez Álvaro, Alberto Moreno Fernandez, Asunción Díaz, Jordi Mancebo Cortés, Francisco Javier De Castro Vega, Álvaro Navarro Batet, Francisco Javier Sagra, Alexandre Pérez González, Luis Castro, Isabel Barrio López, Marta Ruiz-Alguero, Silvia Ossaba-Vélez, Alberto Martín-Vega, Maria Jesus Bustinduy Odriozola, Sivia Pastor-Yvorra, Nuria Espinosa, Elena Múñez Rubio, María E García-Leoni, Sandra Rosillo, Cristina Carbonell, Iván Navas Clemente, Paula Arriola Martínez, Marta Peña, Lucía Martínez de Soto, Roberto Mora-Corcovado, Alberto Iglesias-Sigüenza, Rocío Ruíz-Hueso, Elena Alvar, Pedro Camacho, Jesús Sojo-Dorado, Remedios Alemán Valls, Ines Ponz, Esmeralda Palmier Peláez, María Arcos Rueda, Guillermo Maestro de la Calle, Ramón Pérez Tanoira, Ana Martínez Vidal, Cristina Amodeo, Marina Pacheco Martínez-Atienza, Clara Muñoz Aguirre, Felipe Villar Álvarez, Giorgina Salgueiro, Xavier Sanz Salvador, César Pérez-Romero, Beatriz Álvarez Zapatero, Nelsa González-Aguado, Robert Torres Sánchez del Arco, Enrique Míguez Rey, Merce Sirisi, Xavier Bonfill Cosp, Marta Yagüe-Barrado, Elena Pérez-Costa, Sandra Casares, Eva Estirado, Jorge Alvarez Troncoso, Cristina Martín-Carrasco, Diana Sande Llovo, Melchor Álvarez de Mon Soto, Arantzazu Mera Fidalgo, Francisco Marqués-González, Agustín Valido-Morales, Luis Alberto Nieto Fernández del Campo, Helem Haydee Vilchez, María Rivas-Carmenado, Francisco Moreno, Ignacio Fernández-Fernández, Henar Calvo Sánchez, Ana González-Cordón, Isabel Fernández-Navarro, María Simón Sacristán, Eva Jiménez-González de Buitrago, M. Muñoz, María Laplaza-González, Rosa de Miguel Buckley, Marta Redondo-Gutierrez, Paula Santibáñez Sáenz, Raquel Martínez Goñi, Marta Rico Rodríguez, Carlos Toro-Rueda, Francisco Arnalich, Ana Santiago-Recuerda, Clara Soto Abanedes, María Dolores Herrero Mendoza, Aquilino Sanchez Purificación, Diego Franch Llasat, María Velasco Arribas, Alejandro Martín-Quirós, Jorge Alba Fernández, Elena Ramírez, Amparo López-Bernus, Marta Alvarado, María Rexach Fumaña, Martín Pilares-Barco, Carmen Liébana Martos, Yolanda Martínez Martínez, Nicolas Merchante Gutiérrez, Maria José Asensio, Ianire Virto Peña, Lucía Mejuto-Illade, María Angeles Martinez-López, Pilar López-Pirez, Alejandro Suárez, Cristóbal Manuel Rodríguez Leal, Sara Garcia-Bellido Ruiz, Jorge Guisández Martín, Lucia Cachafeiro, Pedro Gil Divasson, Almudena Quintás-Viqueira, Laura Currás-Sánchez, Alverio Seiz-Martinez, Mario Ruiz-Bastián, Juan José Menéndez, Jorge Orihuela Martín, María Dolores Nieto Martín, Cristina Arévalo, Rebeca Marinas, Susana Casas Rodríguez, Zuriñe Ortiz de Zárate Ibarra, Yolanda Posada Franco, Joan Gómez-Junyent, Ana María Garijo Saiz, Marina Alguacil-Guillén, Ana Alguacil, Esther Aznar Muñoz, Sara Bañón Escandell, Juan Salillas Hernando, Chiara Fanciulli, Rosa Gómez-Gil, Francisco García-Río, Moncef Belhassen-García, Belén Gutierrez Sancerni, Sonia Vega Molpeceres, Inés Suárez-García, Leire Pérez-Latorre, Elena Chamarro Martí, Carmen Rosario Herrero Gil, Belén Gutiérrez-Gutiérrez, Tatiana Mata Forte, Francesca Sánchez Martínez, Lucía Ramos Merino, Santiago Yus, Mº Ángeles Marcos, Susana Martínez-Álvarez, Alexy Inciarte, Manuel Quintana-Díaz, Lucía Serrá, Belén Alejos, Guillem Policarpo Torres, José Román Muñoz del Rey, Irene Blanco-Bartolomé, Alberto Bahamonde Carrasco, Victoria Hernando, Jhon Rojas, David Roa, María Ángeles Garcinuño, Aránzazu Villasante de la Puente, Patricia Pérez-Palacios, Jesús Ruiz Aragón, Valvanera Ibarra Cucalón, Lucía Ortega Enciso, Ismail Zakariya-Yousef Breval, Jorge Navarro López, Gema Barbeito Castiñeiras, Clara Sala Jofre, Nora Molina Torres, Manuel Poyato, Inmaculada Poquet Catala, Virginia Pomar Solchaga, María Pilar Romero-Gómez, Clara Hernández, Helena Mozas Moriñigo, Mercedes Guillamón Sánchez, Zineb Karroud, Arianna Catino, Violeta Ramos Sesma, Santos del Campo, Pilar Fernández-Calle, Ana Fernández Cruz, Fernando Salvador, Rosa Mayayo-Alvira, Pilar Barco Núñez, Ana Isabel Peláez Ballesta, Silvia Suárez Diaz, Beatriz María Sanjuan, Nora Izko Gartzia, Teresa Aldámiz-Echevarría, Cecilia Tortajada Alamilla, Pau Bosch-Nicolau, María del Mar Alonso Socas, Sonia Calzado Isbert, Jose R. Arribas, Juan Fernández-Lahera, Elizabet Petkova Saiz, Eva Jiménez, Gabriela Abelenda-Alonso, Alba Ribera Puig, Pascual Sanabria-Carretero, Sara Rodrigo González, Irene Díaz de la Torre, Tamara Manso Gómez, Carmen Sáez Barberá, Roi Suárez Gil, Paloma García-Clemente, Héctor Meijide Míguez, Elsa Izquierdo-García, Josune Goikoetxea Agirre, Olalla Martínez Macia, Jesús Santos González, Guillermo Jiménez Álvarez, Cristina Marcelo-Calvo, Javier Coy Coy, Isabel Arenas-Berenguer, Julio García Rodríguez, Natalia Yustas-Benitez, Sarai Quirós-Fernández, Marina Noguerol-Gutiérrez, María Adalid Moll, Iván Bloise-Sánchez, Mario José Rodriguez Dominguez, Elena Salamanca, Francisco Mora Gómez, Lucio García-Fraile, Pablo Millán, C Gutiérrez, Montserrat Rodríguez, José Antonio Oteo Revuelta, Joseba Portu Zapirain, Cristina Moreno, Irene Carrillo Acosta, Jorge Calvo, Ana Mariño Callejo, David Romero-Ribate, Blanca Alonso, Elena Muñoz del Val, Elena Resino Foz, Olaia Rodriguez-Fraga, Miguel Villamarín, Irene Amores-Hernández, Laura Muñoz López, Esther García Almodóvar, Ismael Casares Guerrero, Angélica Villanueva-Freije, Nuria Parra Arribas, Montserrat Sanmarti Vilamala, Macarena Lerín-Baratas, Mercedes Castro-Martínez, Melissa Carreres Candela, Lucia Suárez Pérez, Jose Manuel Iturzaeta-Sánchez, Thamires Silva-Freire, José Antonio Peregrina, María Luisa Machado Sicilia, Sergio Zurita, Daniel Molina Morant, Olga González-Peña, Fernando Lázaro-Perona, Paloma Oliver-Saez, Beatriz Mestre-Gómez, Luis Díaz Díez Picazo, Silvia García-Bujalance, Francisco Rodríguez Gómez, Pere Comas Casanova, Carlos Ruiz Martínez, Alberto Delgado-Iribarren, Berta Alonso-González, Isabel Moreno-Parra, Teresa Gómez-Ballesteros, Araceli Menéndez, Jose Manuel Añón, Ruth Jorge García, Jonathan Cámara Fernández, Miguel Górgolas Hernández-Mora, Itziar Diego Yagüe, Miriam Latorre-Millán, Covadonga Morcate Fernández, M. Río-García, Elisabet Lerma-Chippirraz, Carmen Yllera Gutiérrez, Francesc Albertí, Eva Flores, Carmen R. Uña Orejón, Patricio González-Pizarro, Neila Rodriguez-Roca, Miguel Fernández-Huerta, Inés Ferrer Ortiz, María José Blanco Vidal, Juan Pablo Avilés, Alicia Lorenzo Hernández, Mireia Puig Campmany, José Bravo-Ferrer, Gonzalo Martínez-Alés, Pablo Marguenda Contreras, M. Sánchez, Antonio García Pardo, Yolanda Meije, Francisco Tejerina, Carolina Hernández Carballo, Victoria Moreno, Daniel Laorden-Escudero, Ana Barrios Blandino, Alexia Costanza Espiño Álvarez, Ana Milagro Beamonte, Jerónimo Pachón, S San José-Villar, Marta Morando, María del Carmen Navarro Sáez, Rodolfo Álvarez-Sala Walther, Jon Ugalde Espiñeira, Fernando De la Calle Prieto, Nuria Fernández, Iván Pelegrín Senent, Alba Rueda López, Cristina Schüffelmann, Marcelino Hayek Peraza, Laura Labajo-Montero, Angel Robles Marhuenda, Pilar Durán, Ana Esteban-Romero, María Rosa Oltra Sempere, Ana Cosmen Sánchez, Alex Smithson Amat, Margarita Ramírez-Schacke, Marco Antonio Sempere Alcocer, Paloma Carrera-Vázquez, M Miarons, Teresa García Delange, Amelia Rodriguez-Mariblanca, Eva Talavera García, Roberto Vates Gómez, Óscar Sanz Peláez, José María Muñoz-Ramón, José Luis García Fogeda, Isabel Arroyo-Rico, Verónica Cano Llorente, Fernando González-Romo, Alberto Alonso-Babarro, Fátima Brañas, Fabricio Iannuccelli, Pilar Álvarez Padín, Luis Metola Sacristán, Vicente Boix, Víctor Hontañón, Juan Berenguer, José Luís Del Pozo León, Patricia Sorní Moreno, Maria Isabel Torres, Rafael Mican Rivera, Amparo Blasco Claramunt, Carmen Ardanuy, Aychel Elena Roura Piloto, María Ángeles Molina, Isabel Asschert Agüero, Julía Alvárez del Vayo, Consuelo García-Sánchez, Begoña Reche-Martínez, Guillermo Cuervo, Carlos Iniesta, María Antonia Gómez-Mendieta, Ana María Noblejas Mozo, Andres Bartrina-Tarrio, Carmen De la Higuera Arranz, Yeray Untoria Tabares, Andrés Enrique Suárez-Plaza, Jesús Frías, Paloma López-Arévalo, Irene María Llorente-Cortijo, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), and Fundación SEIMC-GESIDA

Subjects
Male, Prognostic variable, medicine.medical_specialty, Databases, Factual, Coronavirus disease 2019 (COVID-19), 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Retrospective Studies, Models, Statistical, SARS-CoV-2, business.industry, Mortality rate, COVID-19, Retrospective cohort study, Articles, Middle Aged, Prognosis, medicine.disease, Phenotype, Hospitals, Hospitalization, Logistic Models, Infectious Diseases, Spain, Cohort, Female, Lymphocytopenia, business, Cohort study
Abstract

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Published
2021

20. SARS-CoV-2 RNAemia is associated with severe chronic underlying diseases but not with nasopharyngeal viral load

Author

José Antonio Oteo-Revuelta, Mónica Gozalo, Patricia Muñoz, Javier Sánchez-Céspedes, Gabriela Abelenda-Alonso, Alexander Rombauts, Álvaro Pascual, Sonia Santibáñez, Jordi Carratalà, Maricela Valerio, Adoración Valiente, Jorge Alba, Patricia Pérez-Palacios, Pedro Camacho-Martínez, Elisa Cordero, Judith Berastegui-Cabrera, Emilio García-Díaz, Maria Luisa Rodríguez-Ferrero, María Carmen Fariñas, Marta Carretero-Ledesma, Jerónimo Pachón, José Miguel Cisneros, Francisco Arnaiz de las Revillas, Sonsoles Salto-Alejandre, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, and Universidad de Cantabria

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Viral Load, Antibodies, Viral, Prognosis, Virology, Infectious Diseases, RNAemia, Disease severity, Nasopharynx, Humans, Medicine, Disease Severity, business, Letter to the Editor, Viral load
Abstract

The kinetics of the SARS-CoV-2 viral load in respiratory airways and other tissues is of great interest to understand the pathogenesis, course, and the management of COVID-19 patients. Therefore, we read with much interest the systematic literature review recently published in the Journal of Infection by Walsh et al.1, concluding that viral load in upper respiratory samples peaks around the time of symptoms onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; moreover, there is evidence of prolonged virus detection in stool samples, with unclear clinical significance. Information regarding the use of other samples to improve patients’ management is lacking or inconsistent.1, 2, 3 Thus, the risk factors for bloodstream infection and the clinical meaning of SARS-CoV-2 RNAemia detection has not yet been completely elucidated., Supported by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/0016/0005, RD16/0016/0007, RD16/0016/0009, RD16/0016/0010, R D16/0016/0013) cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020. JSC and EC received grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación , Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 ( COV20/00580 ; COV20/00370 ). J.S.C. is a researcher belonging to the program “Nicolás Monardes” (C-0059–2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

Published
2020

21. Host- and Pathogen-Related Factors for Acute Cardiac Events in Pneumococcal Pneumonia

Author

Jordi Carratalà, Cristian Tebé, Aida González-Díaz, Alexander Rombauts, Carmen Ardanuy, Jordi Càmara, Enric Sastre-Escolà, Carlota Gudiol, Jordi Dorca, Gabriela Abelenda-Alonso, Natalia Pallares, and Laia Lorenzo-Esteller

Subjects
medicine.medical_specialty, community-acquired pneumonia, pneumococcal pneumonia, Community-acquired pneumonia, Heart diseases, genotype, 030204 cardiovascular system & hematology, Pneumònia adquirida a la comunitat, Major Articles, Malalties del cor, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, acute cardiac events, medicine, serotype, 030212 general & internal medicine, Myocardial infarction, Prospective cohort study, Septic shock, business.industry, Retrospective cohort study, Odds ratio, medicine.disease, Pneumonia, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Pneumococcal pneumonia, business
Abstract

Background Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce. Methods A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs. Results Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11–3.13). Conclusions ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.

Published
2020
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22. Antibody Immunological Imprinting on COVID-19 Patients

Author

Alexander Rombauts, Florian Krammer, Sadaf Aslam, Kaijun Jiang, Daniel Stadlbauer, Fatima Amanat, Gabriela Abelenda-Alonso, Adolfo García-Sastre, Teresa Aydillo, Jordi Carratalà, and Alba Escalera

Subjects
biology, Coronavirus disease 2019 (COVID-19), viruses, virus diseases, respiratory tract diseases, Nucleoprotein, Immune system, Immunity, Polyclonal antibodies, Immunology, biology.protein, Antibody, Imprinting (psychology), Original antigenic sin
Abstract

While the current pandemic remains a thread to human health, the polyclonal nature of the antibody response against SARS-CoV-2 is not fully understood. Other than SARS-CoV-2, humans are susceptible to six different coronaviruses, and previous exposure to antigenically related and divergent seasonal coronaviruses is frequent. We longitudinally profiled the early humoral immune response against SARS-CoV-2 on hospitalized COVID-19 patients, and quantify levels of pre-existing immunity to OC43, HKU1 and 223E seasonal coronaviruses. A strong back-boosting effect to conserved, but not variable regions of OC43 and HKU1 betacoronaviruses spike protein was observed. All patients developed antibodies against SARS-CoV-2 spike and nucleoprotein, with peak induction at day 7 post hospitalization. However a negative correlation was found between antibody memory boost to human coronaviruses and induction of IgG and IgM against SARS-CoV-2 spike. Our findings provide evidence of immunological imprinting that determine the antibody profile to COVID-19 patients in an original antigenic sin fashion.

Published
2020
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23. Impact of comprehensive molecular testing to reduce antibiotic use in community-acquired pneumonia (RADICAP): a randomised, controlled, phase IV clinical trial protocol

Author

Carmen Ardanuy, Lucía Ortega, Cristian Tebé, Gabriela Abelenda-Alonso, Yolanda Meije, Jordi Niubó, Ariadna Padullés, Alexander Rombauts, Sebastián Videla, Mercedes Clemente, Jordi Carratalà, and Carlota Gudiol

Subjects
Adult, medicine.medical_specialty, medicine.drug_class, Antibiotics, Pneumònia, Antibiòtics, Clinical Trials, Phase IV as Topic, law.invention, molecular diagnostics, respiratory infections, Antibiotic resistance, Clinical trials, Community-acquired pneumonia, law, Clinical endpoint, Medicine, Humans, Adverse effect, Randomized Controlled Trials as Topic, business.industry, SARS-CoV-2, COVID-19, General Medicine, Pneumonia, medicine.disease, diagnostic microbiology, Intensive care unit, Anti-Bacterial Agents, Clinical trial, Infectious Diseases, Molecular Diagnostic Techniques, Emergency medicine, business, Assaigs clínics
Abstract

IntroductionCommunity-acquired pneumonia (CAP) continues to be a major health problem worldwide and is one of the main reasons for prescribing antibiotics. However, the causative agent is often not identified, resulting in antibiotic overtreatment, which is a key driver of antimicrobial resistance and adverse events. We aim to test the hypothesis that comprehensive molecular testing, compared with routine microbiological testing, would be effective in reducing antibiotic use in patients with CAP.Methods and analysisWe will perform a randomised, controlled, open-label clinical trial with two parallel groups (1:1) at two tertiary hospitals between 2020 and 2022. Non-severely immunosuppressed adults hospitalised for CAP will be considered eligible. Patients will be randomly assigned to receive either the experimental diagnosis (comprehensive molecular testing plus routine microbiological testing) or standard diagnosis (only microbiological routine testing). The primary endpoint will be antibiotic consumption measured as days of antibiotic therapy per 1000 patient-days. Secondary endpoints will be de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, days to reaching an aetiological diagnosis, antibiotic-related side effects, length of stay, days to clinical stability, intensive care unit admission, days of mechanical ventilation, hospital readmission up to 30 days after randomisation and death from any cause by 48 hours and 30 days after randomisation. We will need to include 440 subjects to be able to reject the null hypothesis that both groups have equal days of antibiotic therapy per 1000 patient-days with a probability >0.8.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Bellvitge Hospital (AC028/19) and from the Spanish Medicines and Medical Devices Agency, and it is valid for all participating centres under existing Spanish legislation. Results will be presented at international meetings and will be made available to patients, their caregivers and funders.Trial registration numberClinicalTrials:NCT04158492. EudraCT: 2018-004880-29.

Published
2020

24. Antibiotic prescription during the COVID-19 pandemic: A biphasic pattern

Author

Alexander Rombauts, Gabriela Abelenda-Alonso, Ramon Jodar, Miquel Pujol, Jordi Carratalà, Carlota Gudiol, Claudia Alvarez-Pouso, and Ariadna Padullés

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Epidemiology, medicine.disease, Virology, Antibiotic prescription, Pneumonia, Biphasic Pattern, Infectious Diseases, Pandemic, medicine, Antimicrobial stewardship, business, Coronavirus Infections
Published
2020
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25. One air, one health: air pollution in the era of antimicrobial resistance

Author

Gabriela Abelenda-Alonso, Alexander Rombauts, Núria Burguillos, and Jordi Carratalà

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Bacteria, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Air pollution, COVID-19, General Medicine, Global Health, medicine.disease_cause, Anti-Bacterial Agents, Infectious Diseases, Antibiotic resistance, One Health, Air Pollution, Environmental health, Drug Resistance, Bacterial, medicine, Humans, business
Published
2021
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26. Influenza and Bacterial Coinfection in Adults With Community-Acquired Pneumonia Admitted to Conventional Wards: Risk Factors, Clinical Features, and Outcomes

Author

Carlota Gudiol, Yolanda Meije, Gabriela Abelenda-Alonso, Alexander Rombauts, Mercedes Clemente, Lucía Ortega, Jordi Niubó, Jordi Carratalà, and Carmen Ardanuy

Subjects
0301 basic medicine, medicine.medical_specialty, Oseltamivir, clinical features, community-acquired pneumonia, Community-acquired pneumonia, 030106 microbiology, Influenzavirus, influenza virus, Pneumònia adquirida a la comunitat, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, law, Internal medicine, Major Article, Medicine, Influenza viruses, 030212 general & internal medicine, Prospective cohort study, business.industry, Mortality rate, prognostic factors, medicine.disease, Intensive care unit, Comorbidity, coinfection, Pneumonia, AcademicSubjects/MED00290, Infectious Diseases, Oncology, chemistry, Coinfection, business
Abstract

Background Relevance of viral and bacterial coinfection (VBC) in non-intensive care unit (ICU) hospitalized adults with community-acquired pneumonia (CAP) is poorly characterized. We aim to determine risk factors, features, and outcomes of VBC-CAP in this setting. Methods This is a prospective cohort of adults admitted to conventional wards with CAP. Patients were divided into VBC-CAP, viral CAP (V-CAP), and bacterial CAP (B-CAP) groups. Independent risk and prognostic factors for VBC-CAP were identified. Results We documented 1123 episodes: 57 (5.1%) VBC-CAP, 98 (8.7%) V-CAP, and 968 (86.1%) B-CAP. Patients with VBC-CAP were younger than those with B-CAP (54 vs 71 years; P, In this study of adults with CAP admitted to conventional wards, we assessed the rate of VBC. This potentially distinct CAP classification presented more often in younger patients with poorer influenza vaccine coverage and was associated with worse outcomes.

Published
2020

27. Daptomycin eosinophilic pneumonia: an adverse effect to be aware of

Author

Gabriela Abelenda-Alonso, Montes Rodríguez I, Martín Torres J, and Del Valle Loarte P

Subjects
Cross Infection, Treatment Outcome, Daptomycin, Adrenal Cortex Hormones, Humans, Drug Therapy, Combination, Female, Middle Aged, Pulmonary Eosinophilia, Arthroplasty, Replacement, Knee, Tomography, X-Ray Computed, Anti-Bacterial Agents
Published
2018

28. Staphylococcus aureus bacteremia in a secondary level Spanish hospital: clinical implications of high vancomycin MIC

Author

Gabriela Abelenda-Alonso, Md, Corbacho Loarte, Núñez Ramos R, Cervero Jiménez M, and Jj, Jusdado Ruiz-Capillas

Subjects
Aged, 80 and over, Male, Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, Original, bacteriemia persistente, Bacteremia, Vancomycin Resistance, Microbial Sensitivity Tests, CMI alta a vancomicina, Middle Aged, Staphylococcal Infections, persistent bacteremia, high vancomycin MIC, bacteriemia por Staphylococcus aureus, Spain, Catheter-Related Infections, Humans, Female, Staphylococcus aureus bacteremia, Secondary Care Centers, Aged, Retrospective Studies
Abstract

Background One of the most controversial issues in recent years has been the clinical significance of high vancomycin MIC in Staphylococcus aureus bacteremia. The aim of this study was to elucidate the clinical implication that this parameter has in the staphylococcal bacteremia of a second level hospital. Material and methods Retrospective descriptive study between January 2014 and September 2016 with 138 records from the blood culture Severo Ochoa University Hospital registry. A total of 98 cases were finally analized. Microbiological analysis of vancomycin MIC was performed using micro dilution technique. Results The mean age was 71.4 ± 12.45 and 63.26% of the patients had a Charlson index ≥6. A 30.61% were carriers of a venous central catheter. The most frequent source was venous central catheter (26.53%). There were 14.24% metastatic events. Global mortality rate at 30 days was 25.51%. The 43.87% of strains had a vancomycin MIC ≥ 2 mg/L. High vancomycin MIC was significantly associated with persistent bacteremia (OR 3.12 [1.13-8.93]), maintaining this statistical significance in methicillin-resistant S. aureus (MRSA) group (p =0.001) but no in methicillin-susceptible S. aureus (MSSA) group (p = 0.13). Persistent bacteremia was also significantly related with permanent catheter carriers (OR 4.18 [1.38-12.61]), peripheric catheter source (OR 5.18 [1.13-8.93]) and metastatic complications (OR 3.82 [1.03-12.81]). There was no significant association between high vancomycin MIC and mortality. Conclusions High vancomycin MIC may be useful in daily clinical practice as a marker of poor clearance of S. aureus bacteremia, specially when is due to MRSA strains.

29. Staphylococcus aureus bacteremia in a secondary level Spanish hospital: clinical implications of high vancomycin MIC.

Author

Abelenda Alonso G, Corbacho Loarte MD, Núñez Ramos R, Cervero Jiménez M, and Jusdado Ruiz-Capillas JJ

Subjects
Aged, Aged, 80 and over, Bacteremia blood, Catheter-Related Infections epidemiology, Catheter-Related Infections microbiology, Female, Humans, Male, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Middle Aged, Retrospective Studies, Secondary Care Centers, Spain, Staphylococcal Infections blood, Staphylococcal Infections mortality, Bacteremia microbiology, Staphylococcal Infections microbiology, Staphylococcus aureus drug effects, Vancomycin Resistance
Abstract

Objective: One of the most controversial issues in recent years has been the clinical significance of high vancomycin MIC in Staphylococcus aureus bacteremia. The aim of this study was to elucidate the clinical implication that this parameter has in the staphylococcal bacteremia of a second level hospital., Methods: Retrospective descriptive study between January 2014 and September 2016 with 138 records from the blood culture Severo Ochoa University Hospital registry. A total of 98 cases were finally analized. Microbiological analysis of vancomycin MIC was performed using micro dilution technique., Results: The mean age was 71.4 ± 12.45 and 63.26% of the patients had a Charlson index ≥6. A 30.61% were carriers of a venous central catheter. The most frequent source was venous central catheter (26.53%). There were 14.24% metastatic events. Global mortality rate at 30 days was 25.51%. The 43.87% of strains had a vancomycin MIC ≥ 2 mg/L. High vancomycin MIC was significantly associated with persistent bacteremia (OR 3.12 [1.13-8.93]), maintaining this statistical significance in methicillin-resistant S. aureus (MRSA) group (p =0.001) but no in methicillin-susceptible S. aureus (MSSA) group (p = 0.13). Persistent bacteremia was also significantly related with permanent catheter carriers (OR 4.18 [1.38-12.61]), peripheric catheter source (OR 5.18 [1.13-8.93]) and metastatic complications (OR 3.82 [1.03- 12.81]). There was no significant association between high vancomycin MIC and mortality., Conclusions: High vancomycin MIC may be useful in daily clinical practice as a marker of poor clearance of S. aureus bacteremia, specially when is due to MRSA strains., (©The Author 2018. 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/).)

Published
2018

30. Daptomycin eosinophilic pneumonia: an adverse effect to be aware of.

Author

Abelenda Alonso G, Montes Rodríguez I, Martín Torres J, and Del Valle Loarte P

Subjects
Adrenal Cortex Hormones therapeutic use, Anti-Bacterial Agents therapeutic use, Arthroplasty, Replacement, Knee, Cross Infection drug therapy, Cross Infection microbiology, Daptomycin therapeutic use, Drug Therapy, Combination, Female, Humans, Middle Aged, Pulmonary Eosinophilia diagnostic imaging, Tomography, X-Ray Computed, Treatment Outcome, Anti-Bacterial Agents adverse effects, Daptomycin adverse effects, Pulmonary Eosinophilia drug therapy
Published
2018

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