Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis.

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Early Recognition of Low-Risk SARS-CoV-2 Pneumonia: A Model Validated With Initial Data and Infectious Diseases Society of America/American Thoracic Society Minor Criteria.

BACKGROUND: A shortage of beds in ICUs and conventional wards during the COVID-19 pandemic led to a collapse of health care resources. RESEARCH QUESTION: Can admission data and minor criteria by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) help identify patients with low-risk SARS-CoV-2 pneumonia? STUDY DESIGN AND METHODS: This multicenter cohort study included 1,274 patients in a derivation cohort and 830 (first wave) and 754 (second wave) patients in two validation cohorts. A multinomial regression analysis was performed on the derivation cohort to compare the following patients: those admitted to the ward (assessed as low risk); those admitted to the ICU directly; those transferred to the ICU after general ward admission; and those who died. A regression analysis identified independent factors for low-risk pneumonia. The model was subsequently validated. RESULTS: In the derivation cohort, similarities existed among those either directly admitted or transferred to the ICU and those who died. These patients could, therefore, be merged into one group. Five independently associated factors were identified as being predictors of low risk (not dying and/or requiring ICU admission) (ORs, with 95% CIs): peripheral blood oxygen saturation/Fio2 > 450 (0.233; 0.149-0.364); < 3 IDSA/ATS minor criteria (0.231; 0.146-0.365); lymphocyte count > 723 cells/mL (0.539; 0.360-0.806); urea level < 40 mg/dL (0.651; 0.426-0.996); and C-reactive protein level < 60 mg/L (0.454; 0.285-0.724). The areas under the curve were 0.802 (0.769-0.835) in the derivation cohort, and 0.779 (0.742-0.816) and 0.801 (0.757-0.845) for the validation cohorts (first and second waves, respectively). INTERPRETATION: Initial biochemical findings and the application of < 3 IDSA/ATS minor criteria make early identification of low-risk SARS-CoV-2 pneumonia (approximately 80% of hospitalized patients) feasible. This scenario could facilitate and streamline health care resource allocation for patients with COVID-19.

Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors.

INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.

INTRODUCCIÓN: Existe controversia respecto al uso de los inhibidores de la enzima convertidora de angiotensina (IECA) o los bloqueadores de los receptores tipo I de la angiotensina II (ARA-II) para el tratamiento de la hipertensión arterial en COVID-19. Se ha sugerido que estos fármacos podrían tanto aumentar como reducir el riesgo de COVID-19 grave. PACIENTES Y MÉTODO: Estudio de cohortes retrospectivo de pacientes consecutivos de un área sanitaria, con hipertensión e infección por SARS-CoV-2. Variable de resultados: ingreso hospitalario por COVID-19 grave. RESULTADOS: Fueron diagnosticados 539 sujetos por infección por SARS-CoV-2. De estos, 157 (29,1%) eran hipertensos y se incluyeron en el estudio. Se ingresaron 69 (43,9%) pacientes por COVID-19 grave. En el análisis multivariante, la edad más elevada, la diabetes y la miocardiopatía hipertensiva se relacionaron con el riesgo de ingreso hospitalario. El tratamiento con ARA-II se asoció con un riesgo significativamente más bajo de ingreso (HR: 0,29, IC 95%: 0,10-0,88). Una tendencia similar, aunque no significativa, se encontró para los IECA. CONCLUSIÓN: el tratamiento con ARA-II o IECA no se asoció con una peor evolución clínica en pacientes hipertensos consecutivos infectados por SARS-CoV-2.

Short and Long-Term Impact of COVID-19 Infection on Previous Respiratory Diseases.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.

COVID-19 pneumonia in Galicia (Spain): Impact of prognostic factors and therapies on mortality and need for mechanical ventilation.

INTRODUCTION: This study was aimed to identify risk factors associated with unfavorable outcomes (composite outcome variable: mortality and need for mechanical ventilation) in patients hospitalized in Galicia with COVID-19 pneumonia. METHODS: Retrospective, multicenter, observational study carried out in the 8 Galician tertiary hospitals. All Patients admitted with confirmed COVID-19 pneumonia from 1st of March to April 24th, 2020 were included. A multivariable logistic regression analysis was performed in order to identify the relationship between risk factors, therapeutic interventions and the composite outcome variable. RESULTS: A total of 1292 patients (56.1% male) were included. Two hundred and twenty-five (17.4%) died and 327 (25.3%) reached the main outcome variable. Age [odds ratio (OR) = 1.03 (95% confidence interval (CI): 1.01-1.04)], CRP quartiles 3 and 4 [OR = 2.24 (95% CI: 1.39-3.63)] and [OR = 3.04 (95% CI: 1.88-4.92)], respectively, Charlson index [OR = 1.16 (95%CI: 1.06-1.26)], SaO2 upon admission [OR = 0.93 (95% CI: 0.91-0.95)], hydroxychloroquine prescription [OR = 0.22 (95%CI: 0.12-0.37)], systemic corticosteroids prescription [OR = 1.99 (95%CI: 1.45-2.75)], and tocilizumab prescription [OR = 3.39 (95%CI: 2.15-5.36)], significantly impacted the outcome. Sensitivity analysis using different alternative logistic regression models identified consistently the ratio admissions/hospital beds as a predictor of the outcome [OR = 1.06 (95% CI: 1.02-1.11)]. CONCLUSION: These findings may help to identify patients at hospital admission with a higher risk of death and may urge healthcare authorities to implement policies aimed at reducing deaths by increasing the availability of hospital beds.

Hospital Epidemics Tracker (HEpiTracker): Description and pilot study of a mobile app to track COVID-19 in hospital workers.

BACKGROUND: Hospital workers have been the most frequently and severely affected professional group during the COVID-19 pandemic, and have a big impact on transmission. In this context, innovative tools are required to measure the symptoms compatible with COVID-19, the spread of infection, and testing capabilities within hospitals in real time. OBJECTIVE: We aimed to develop and test an effective and user-friendly tool to identify and track symptoms compatible with COVID-19 in hospital workers. METHODS: We developed and pilot tested Hospital Epidemics Tracker (HEpiTracker), a newly designed app to track the spread of COVID-19 among hospital workers. Hospital staff in 9 hospital centers across 5 Spanish regions (Andalusia, Balearics, Catalonia, Galicia, and Madrid) were invited to download the app on their phones and to register their daily body temperature, COVID-19-compatible symptoms, and general health score, as well as any polymerase chain reaction and serological test results. RESULTS: A total of 477 hospital staff participated in the study between April 8 and June 2, 2020. Of note, both health-related (n=329) and non-health-related (n=148) professionals participated in the study; over two-thirds of participants (68.8%) were health workers (43.4% physicians and 25.4% nurses), while the proportion of non-health-related workers by center ranged from 40% to 85%. Most participants were female (n=323, 67.5%), with a mean age of 45.4 years (SD 10.6). Regarding smoking habits, 13.0% and 34.2% of participants were current or former smokers, respectively. The daily reporting of symptoms was highly variable across participating hospitals; although we observed a decline in adherence after an initial participation peak in some hospitals, other sites were characterized by low participation rates throughout the study period. CONCLUSIONS: HEpiTracker is an already available tool to monitor COVID-19 and other infectious diseases in hospital workers. This tool has already been tested in real conditions. HEpiTracker is available in Spanish, Portuguese, and English. It has the potential to become a customized asset to be used in future COVID-19 pandemic waves and other environments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04326400; https://clinicaltrials.gov/ct2/show/NCT04326400.