Persistent COVID-19 symptoms 1 year after hospital discharge: A prospective multicenter study

Objective To determine the health status and exercise capacity of COVID-19 survivors one year after hospital discharge. Methods This multicenter prospective study included COVID-19 survivors 12 months after hospital discharge. Participants were randomly selected from a large cohort of COVID-19 patients who had been hospitalized until 15th April 2020. They were interviewed about persistent symptoms, underwent a physical examination, chest X-ray, and a 6-minute walk test (6MWT). A multivariate analysis was performed to determine the risk factors for persistent dyspnea. Results Of the 150 patients included, 58% were male and the median age was 63 (IQR 54-72) years. About 82% reported >= 1 symptoms and 45% had not recovered their physical health. The multivariate regression analysis revealed that the female sex, chronic obstructive pulmonary disease, and smoking were independent risk factors for persistent dyspnea. Approximately 50% completed less than 80% of the theoretical distance on the 6MWT. Only 14% had an abnormal X-ray, showing mainly interstitial infiltrates. A third of them had been followed up in outpatient clinics and 6% had undergone physical rehabilitation. Conclusion Despite the high rate of survivors of the first wave of the COVID-19 pandemic with persistent symptomatology at 12 months, the follow-up and rehabilitation of these patients has been really poor. Studies focusing on the role of smoking in the persistence of COVID-19 symptoms are lacking

Changing Trends in the Global Consumption of Treatments Used in Hospitalized Patients for COVID-19: A Time Series Multicentre Study

Aim: To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. Methods: Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. Results: The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. Conclusions: Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials

Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19

Objective To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Methods Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Results Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p.298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. Conclusion There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Biomarcadores diagnósticos y de actividad en el Síndrome de Sjögren Primario

L'objectiu d'aquesta tesi doctoral va ser avaluar la utilitat de les subpoblacions limfocitàries en sang perifèrica i dels nivells sèrics de BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 i PD-L2 com a biomarcadors diagnòstics i d'activitat a la síndrome de Sjögren primari (SSp). Per això es van realitzar dos estudis observacionals a l'Hospital Universitari Vall d'Hebron entre abril 2014 i setembre 2017. Tots els pacients amb SSp complien els criteris classificatoris de l'AECG del 2002. Al primer estudi es van incloure 68 pacients amb SSp, 26 pacients amb síndrome seca no-Sjögren i 23 voluntaris sans, i es va analitzar la distribució de les poblacions limfocitàries circulants mitjançant citometria de flux. Els pacients amb SSp presentaven menor proporció de limfòcits B de memòria i majors proporcions de limfòcits B naïve (BNA) i limfòcits T activats. La proporció de limfòcits B de memòria non-switched (BNSM) va resultar el millor paràmetre individual per diferenciar entre pacients amb SSp i pacients amb síndrome seca no-Sjögren (sensibilitat 72% i especificitat 76,6% per a un punt de tall 9 (AUC 0,789). El millor paràmetre diagnòstic va ser el quocient entre el percentatge de limfòcits BNSM i el de limfòcits T CD4+ activats (CD4ACT), que amb un punt de tall 0 van presentar concentracions sèriques més elevades de CXCL13 (696,9 vs. 359,8 pg/mL; p=0,0091), IL-21 (311,1 vs. 49,8 pg/mL ; p=0,0461), IL-22 (98,4 vs. 59,1 pg/mL; p=0,0464) i TNF-R2 (278,8 vs. 207,4 pg/mL; p=0,0164). Els nivells sèrics d'IgG es van correlacionar amb els nivells d'IL-21 (r=0,553; p240 pg/mL, AUC 0,799). El millor paràmetre diagnòstic va ser la fórmula [ln(CXCL13)+ln(BAFF)]/ln(PD-L2), que amb un punt de tall >1,7 va mostrar una sensibilitat de 77,2% i una especificitat de 86,4% (AUC 0,854).El objetivo de esta tesis doctoral fue evaluar la utilidad de las subpoblaciones linfocitarias en sangre periférica y de los niveles séricos de BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 y PD-L2 como biomarcadores diagnósticos y de actividad en el síndrome de Sjögren primario (SSp). Para ello se realizaron dos estudios observacionales en el Hospital Universitari Vall d'Hebron entre abril 2014 y septiembre 2017. Todos los pacientes con SSp cumplían los criterios clasificatorios del AECG de 2002. En el primer estudio se incluyeron 68 pacientes con SSp, 26 pacientes con síndrome seco no-Sjögren y 23 voluntarios sanos, y se analizó la distribución de las poblaciones linfocitarias circulantes mediante citometría de flujo. Los pacientes con SSp presentaban menor proporción de linfocitos B de memoria y mayores proporciones de linfocitos B naïve (BNA) y linfocitos T activados. La proporción de linfocitos B de memoria non-switched (BNSM) resultó el mejor parámetro individual para diferenciar entre pacientes con SSp y pacientes con síndrome seco no-Sjögren (sensibilidad 72% y especificidad 76,6% para un punto de corte 9 (AUC 0,789). El mejor parámetro diagnóstico fue el cociente entre el porcentaje de linfocitos BNSM y el de linfocitos T CD4+ activados (CD4ACT), que con un punto de corte 0 presentaron concentraciones séricas más elevadas de CXCL13 (696,9 vs. 359,8 pg/mL; p=0,0091), IL-21 (311,1 vs. 49,8 pg/mL; p=0,0461), IL-22 (98,4 vs. 59,1 pg/mL; p=0,0464) y TNF-R2 (278,8 vs. 207,4 pg/mL; p=0,0164). Los niveles séricos de IgG se correlacionaron con los niveles de IL-21 (r=0,553; p240 pg/mL, AUC 0,799). El mejor parámetro diagnóstico fue la fórmula [ln(CXCL13)+ln(BAFF)]/ln(PD-L2), que con un punto de corte >1,7 mostró una sensibilidad de 77,2% y una especificidad de 86,4% (AUC 0,854).The objective of this doctoral Thesis was to evaluate the utility of lymphocyte subpopulations in peripheral blood and the serum levels of BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 as diagnostic and disease activity biomarkers in patients with primary Sjögren's syndrome (pSS). Two observational studies were carried out at the Vall d'Hebron University Hospital between April 2014 and September 2017. All patients with pSS met the 2002 AECG classification criteria. The first study included 68 patients with pSS, 26 patients with non-Sjögren sicca syndrome and 23 healthy volunteers, and the distribution of circulating lymphocyte populations was analysed using flow cytometry. Patients with pSS showed a reduced proportion of memory B lymphocytes and an increased proportion of naïve B lymphocytes and activated T lymphocytes. The percentage of non-switched memory B lymphocytes was the best individual parameter to differentiate between patients with pSS and patients with non-Sjögren sicca syndrome, yielding a sensitivity of 72% and a specificity of 76.6% using a cut-off point 9 (AUC 0.789). The best diagnostic parameter was the ratio between the percentages of non-switched memory B lymphocytes and activated CD4+ T lymphocytes, which showed a sensitivity of 83.3% and a specificity of 81.7% using a cut-off point 0 showed higher serum concentrations of CXCL13 (696.9 vs. 359.8 pg/mL, p=0.0091), IL-21 (311.1 vs. 49.8 pg/mL, p=0.0461), IL-22 (98.4 vs. 59.1 pg/mL, p=0.0464) and TNF-R2 (278.8 vs. 207.4 pg/mL, p=0.0164). Serum IgG levels correlated with serum levels of IL-2 (r=0.553, p240 pg/mL). However, the best diagnostic parameter was the formula [ln(CXCL13)+ln(BAFF)]/ln(PD-L2), which yielded a sensitivity of 77.2% and a specificity of 86.4% using a cut-off point >1.7 (AUC 0.854).Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

Non-intravenous carbapenem-sparing antibiotics for definitive treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL) or AmpC beta-lactamase: A propensity score study

Carbapenems are considered the treatment of choice for extended-spectrum β-lactamase (ESBL)- or AmpC β-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004–2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5–10) days vs. 12 (9–18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05–1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94–26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results.CP, NF-H and JR-B are 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 and 0003], which is co-financed by the European Regional Development Fund ?A way to achieve Europe?, Operative Programme Intelligent Growth 2014?2020

COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA

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Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model

Objectives: We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes. Methods: We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model. Results: There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344). Conclusions: The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes

Clinical Characteristics and Risk Factors of Respiratory Failure in a Cohort of Young Patients Requiring Hospital Admission with SARS-CoV2 Infection in Spain: Results of the Multicenter SEMI-COVID-19 Registry.

Age is a risk factor for COVID severity. Most studies performed in hospitalized patients with SARS-CoV2 infection have shown an over-representation of older patients and consequently few have properly defined COVID-19 in younger patients who require hospital admission. The aim of the present study was to analyze the clinical characteristics and risk factors for the development of respiratory failure among young (18 to 50 years) hospitalized patients with COVID-19. This retrospective nationwide cohort study included hospitalized patients from 18 to 50 years old with confirmed COVID-19 between March 1, 2020, and July 2, 2020. All patient data were obtained from the SEMI-COVID Registry. Respiratory failure was defined as the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) ≤200 mmHg or the need for mechanical ventilation and/or high-flow nasal cannula or the presence of acute respiratory distress syndrome. During the recruitment period, 15,034 patients were included in the SEMI-COVID-19 Registry, of whom 2327 (15.4%) were younger than 50 years. Respiratory failure developed in 343 (14.7%), while mortality occurred in 2.3%. Patients with respiratory failure showed a higher incidence of major adverse cardiac events (44 (13%) vs 14 (0.8%), p320 U/I (OR, 1.69; 95% CI, 1.18 to 2.42; p=0.0039), AST >35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium 35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium 8 mg/dL (OR, 2.42; 95% CI, 1.72 to 3.41; p Young patients with COVID-19 requiring hospital admission showed a notable incidence of respiratory failure. Obesity, SAHS, alcohol abuse, and certain laboratory parameters were independently associated with the development of this complication. Patients who suffered respiratory failure had a higher mortality and a higher incidence of major cardiac events, venous thrombosis, and hospital stay