Retrospective study of the effect of vaccination against SARS-CoV-2 in seriously ill patients admitted to an intensive care unit. / Estudio retrospectivo del efecto de la vacunación frente al SARS-CoV-2 en enfermos graves que ingresan en una unidad de cuidados intensivos.

BACKGROUND AND OBJECTIVE: Our study aims to compare the clinical and epidemiological characteristics, length of stay in the ICU, and mortality rates of COVID-19 patients admitted to the ICU who are fully vaccinated, partially vaccinated, or unvaccinated. PATIENTS AND METHODS: Retrospective cohort study (March 2020-March 2022). Patients were classified into unvaccinated, fully vaccinated, and partially vaccinated groups. We initially performed a descriptive analysis of the sample, a multivariable survival analysis adjusting for a Cox regression model, and a 90-day survival analysis using the Kaplan-Meier method for the death time variable. RESULTS: A total of 894 patients were analyzed: 179 with full vaccination, 32 with incomplete vaccination, and 683 were unvaccinated. Vaccinated patients had a lower incidence (10% vs. 21% and 18%) of severe ARDS. The survival curve did not show any differences in the probability of surviving for 90 days among the studied groups (p = 0.898). In the Cox regression analysis, only the need for mechanical ventilation during admission and the value of LDH (per unit of measurement) in the first 24 hours of admission were significantly associated with mortality at 90 days (HR: 5.78; 95% CI: 1.36-24.48); p = 0.01 and HR: 1.01; 95% CI: 1.00-1.02; p = 0.03, respectively. CONCLUSIONS: Patients with severe SARS-CoV-2 disease who are vaccinated against COVID-19 have a lower incidence of severe ARDS and mechanical ventilation than unvaccinated patients.

Estudio retrospectivo del efecto de la vacunación frente al SARS-CoV-2 en enfermos graves que ingresan en una unidad de cuidados intensivos Retrospective study of the effect of vaccination against SARS-CoV-2 in seriously ill patients admitted to an intensive care unit

Antecedentes y objetivo: Planteamos nuestro trabajo con el objetivo de comparar las características clínico epidemiológicas, la estancia en la UCI y la mortalidad de pacientes con COVID-19 que ingresaron en la UCI con vacunación completa, incompleta o sin vacunar. Pacientes y métodos: Estudio retrospectivo de cohortes (Marzo 2020-Marzo 2022). Los pacientes fueron clasificados en pacientes no vacunados, pauta de vacunación completa y pauta de vacunación incompleta. Se realizó inicialmente un análisis descriptivo de la muestra, un análisis multivariable de la supervivencia ajustando un modelo de regresión de Cox y un análisis de supervivencia a 90 días con el método de Kaplan-Meier para la variable de tiempo de muerte. Resultados: Fueron analizados los 894 pacientes: 179 con una pauta de vacunación completa, 32 con una pauta incompleta y 683 no estaban vacunados. Los enfermos vacunados presentaron con menor frecuencia (10% frente al 21% y 18%) un SDRA grave. La curva de supervivencia, no presentó diferencias en la probabilidad de sobrevivir a los 90 días entre los grupos estudiados (p=0,898). En el análisis de regresión de COX, únicamente la necesidad de VM durante el ingreso y el valor de LDH (por unidad de medida) en las primeras 24 horas de ingreso se asociaron de forma significativa con la mortalidad a los 90 días (HR: 5,78;IC95%: 1,36-24,48);p=0,01 y HR: 1,01;IC95%: 1,00-1,02;p=0,03 respectivamente. Conclusiones: Los pacientes vacunados frente al COVID-19 con enfermedad grave por SARS-CoV-2 presentan unas tasas de SDRA grave y de VM menores que las de aquellos pacientes no vacunados

[The Bayes factor in the analysis of mechanical power in patients with severe respiratory failure due to SARS-CoV-2]. / El método del factor de Bayes en el análisis de la energía mecánica en pacientes con insuficiencia respiratoria grave por SARS-CoV-2.

Objective: To specify the degree of probative force of the statistical hypotheses in relation to mortality at 28 days and the threshold value of 17 J/min mechanical power (MP) in patients with respiratory failure secondary to SARS-CoV-2. Design: Cohort study, longitudinal, analytical. Setting: Intensive care unit of a third level hospital in Spain. Patients: Patients admitted for SARS-CoV-2 infection with admission to the ICU between March 2020 and March 2022. Interventions: Bayesian analysis with the beta binomial model. Main variables of interest: Bayes factor, mechanical power. Results: A total of 253 patients were analyzed. Baseline respiratory rate (BF10: 3.83 × 106), peak pressure value (BF10: 3.72 × 1013) and neumothorax (BF10: 17,663) were the values most likely to be different between the two groups of patients compared. In the group of patients with MP < 17 J/min, a BF10 of 12.71 and a BF01 of 0.07 were established with an 95%CI of 0.27-0.58. For the group of patients with MP ≥ 17 J/min the BF10 was 36,100 and the BF01 of 2.77e-05 with an 95%CI of 0.42-0.72. Conclusions: A MP ≥ 17 J/min value is associated with extreme evidence with 28-day mortality in patients requiring MV due to respiratory failure secondary to SARS-CoV-2 disease.

The Bayes factor in the analysis of mechanical power in patients with severe respiratory failure due to SARS-CoV-2.

OBJECTIVE: To specify the degree of probative force of the statistical hypotheses in relation to mortality at 28 days and the threshold value of 17 J/min mechanical power (MP) in patients with respiratory failure secondary to SARS-CoV-2. DESIGN: Cohort study, longitudinal, analytical. SETTING: Intensive care unit of a third level hospital in Spain. PATIENTS: Patients admitted for SARS-CoV-2 infection with admission to the ICU between March 2020 and March 2022. INTERVENTIONS: Bayesian analysis with the beta binomial model. MAIN VARIABLES OF INTEREST: Bayes factor, mechanical power. RESULTS: A total of 253 patients were analyzed. Baseline respiratory rate (BF10: 3.83 × 106), peak pressure value (BF10: 3.72 × 1013) and neumothorax (BF10: 17,663) were the values most likely to be different between the two groups of patients compared. In the group of patients with MP < 17 J/min, a BF10 of 12.71 and a BF01 of 0.07 were established with an 95%CI of 0.27-0.58. For the group of patients with MP ≥ 17 J/min the BF10 was 36,100 and the BF01 of 2.77e-05 with an 95%CI of 0.42-0.72. CONCLUSIONS: A MP ≥ 17 J/min value is associated with extreme evidence with 28-day mortality in patients requiring MV due to respiratory failure secondary to SARS-CoV-2 disease.

Association of mechanical power and 28-day mortality in patients with severe respiratory failure due to SARS-CoV-2 Asociación de la potencia mecánica y la mortalidad a 28 días en pacientes con insuficiencia respiratoria grave por SARS-CoV-2

Objective To specify the degree of probative force of the statistical hypotheses in relation to mortality at 28 days and the threshold value of 17 J/min mechanical power (MP) in patients with respiratory failure secondary to SARS-CoV-2. Design Cohort study, longitudinal, analytical. Setting Intensive care unit of a third level hospital in Spain. Patients Patients admitted for SARS-CoV-2 infection with admission to the ICU between March 2020 and March 2022. Interventions Bayesian analysis with the beta binomial model. Main variables of interest Bayes factor, mechanical power. Results A total of 253 patients were analyzed. Baseline respiratory rate (BF10: 3.83 × 106), peak pressure value (BF10: 3.72 × 1013) and neumothorax (BF10: 17,663) were the values most likely to be different between the two groups of patients compared. In the group of patients with MP < 17 J/min, a BF10 of 12.71 and a BF01 of 0.07 were established with an 95%CI of 0.27-0.58. For the group of patients with MP ≥ 17 J/min the BF10 was 36,100 and the BF01 of 2.77e-05 with an 95%CI of 0.42-0.72. Conclusions A MP ≥ 17 J/min value is associated with extreme evidence with 28-day mortality in patients requiring MV due to respiratory failure secondary to SARS-CoV-2 disease.

Asociación de la potencia mecánica y la mortalidad a 28 días en pacientes con insuficiencia respiratoria grave por SARS-CoV-2 Association of mechanical power and 28-day mortality in patients with severe respiratory failure due to SARS-CoV-2

Objetivo: precisar el grado de fuerza probatoria de las hipótesis estadísticas en relación a la mortalidad a 28 días y el valor umbral de 17 J/min de potencia mecánica (PM) en pacientes con insuficiencia respiratoria secundaria a SARS-CoV-2. Diseño: estudio de cohortes, longitudinal, analítico. Ámbito: Unidad de Cuidados Intensivos de un Hospital de Tercer Nivel en España. Pacientes: enfermos ingresados por infección por SARS-CoV-2 con ingreso en UCI entre Marzo de 2020 y Marzo de 2022 Intervenciones: análisis bayesiano con el modelo binomial beta. Variables de interés principales: Factor de Bayes, Mechanical Power. Resultados: Fueron analizados 253 pacientes. La frecuencia respiratoria inicial (BF10: 3.83x106), el valor de la Presión Pico (BF10: 3.72x1013) y el desarrollo de neumotórax (BF10: 17663) fueron los valores con más probabilidad de ser diferentes entre los dos grupos de pacientes comparados. En el grupo de pacientes con PM<17 J/min se estableció un BF10 de 12,71 y un BF01 de 0,07 con un IdC95% de 0,27-0,58;Para el grupo de pacientes con PM≥ 17J/min el BF10 fue de 36100 y el BF01 de 2.77e-05 con un IdC95% de 0,42-0,72. Conclusiones: un valor de PM≥17 J/min se asocia con una evidencia extrema con la mortalidad a 28 días en pacientes que necesitaron VM por insuficiencia respiratoria secundaria a enfermedad por SARS-CoV-2.

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.

Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients.

INTRODUCTION: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. METHODS: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. RESULTS: The median [p25-p75] time from discharge to follow-up was 3.57 [2.77-4.92] months. Median age was 60 [53-67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO<80% and 24% having DLCO<60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO<60% were chronic lung disease (CLD) (OR: 1.86 (1.18-2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37-1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18-1.63)), urea (OR: 1.16 (0.97-1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73-1.06)). Bacterial pneumonia (1.62 (1.11-2.35)) and duration of ventilation (NIMV (1.23 (1.06-1.42), IMV (1.21 (1.01-1.45)) and prone positioning (1.17 (0.98-1.39)) were associated with fibrotic lesions. CONCLUSION: Age and CLD, reflecting patients' baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities.

Coste-efectividad de la oxigenoterapia de alto flujo en el tratamiento de la neumonía por SARS-CoV-2 Cost-effectiveness analysis High flow oxygen therapy in the treatment of SARS-CoV-2 pneumonia

Introducción: las cánulas nasales de alto flujo de oxígeno en pacientes con insuficiencia respiratoria secundaria a neumonía por SARS-CoV-2 no han sido estudiadas desde un punto de vista coste-efectividad. Métodos: Análisis retrospectivo de datos obtenidos de enfermos ingresados en área-COVID de un servicio de medicina intensiva en un hospital de referencia de tercer nivel, entre marzo-diciembre de 2020. Se efectuó un análisis de coste efectividad en el que se comparan dos decisiones terapéuticas: la estrategia experimental se definió como una estrategia mixta consistente en la aplicación inicial de HFNO y aplicación de VNI sólo a los fracasos del HFNO. El objetivo del estudio fue establecer cuál de las dos alternativas se presentaba como la decisión racional óptima y la de mejor eficiencia económica (Razón de Coste-Efectividad Incremental por años de vida ganados). Resultados: En el análisis de coste-efectividad, comparando ambas estrategias terapéuticas, la probabilidad de que fuese más efectiva la estrategia experimental fue de 0,974, alcanzando la significación estadística: Diferencia de proporciones media = -0,113;IC 95% = -0,018 a -0,208. Ello corresponde a un NNT de 9 pacientes. La decisión óptima fue la estrategia de HFNO seguida de VMI en los fracasos del HFNO. Esta opción tuvo un RCEI de 5.582 euros por año de vida ganado. Conclusiones: Resulta importante establecer en el futuro marcadores fiables en el empleo del HFNO para que dicha terapia mejore sus prestaciones coste-efectivas.

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study.

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Funding: ISCIII, UNESPA, CIBERES, FEDER, ESF.

Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units Metodología de un gran estudio observacional multicéntrico de pacientes con COVID-19 en unidades de cuidados intensivos en España

Introduction The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. Methods CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. Results This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. Conclusions We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.

ICU-Acquired Pneumonia Is Associated with Poor Health Post-COVID-19 Syndrome.

BACKGROUND: Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. METHODS: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. RESULTS: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. CONCLUSIONS: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-19.