Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

Fulminant myocarditis following SARS-CoV-2 mRNA vaccination rescued with venoarterial ECMO: A report of two cases.

INTRODUCTION: Cases of myocarditis after COVID-19 messenger RNA (mRNA) vaccines administration have been reported. Although the majority follow a mild course, fulminant presentations may occur. In these cases, cardiopulmonary support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) may be needed. RESULTS: We present two cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-CoV2 vaccine. One of the cases was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab using the Seldinger technique. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Whereas an endomyocardial biopsy was performed in both, a definite microscopic diagnosis just could be reached in one of them. Treatment was the same, using 1000mg of methylprednisolone/day for three days. A cardiac magnetic resonance was performed ten days after admission, showing a significant improvement of the left ventricular ejection fraction and diffuse oedema and subepicardial contrast intake in different segments. Both cases were discharged fully recovered, with CPC 1. CONCLUSIONS: COVID-19 vaccine-associated fulminant myocarditis has a high morbidity and mortality but presents a high potential for recovery. V-A ECMO should be established in cases with refractory cardiogenic shock during the acute phase.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study.

QUESTION: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. MATERIALS AND METHODS: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. RESULTS: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. CONCLUSIONS: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

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.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study.

BACKGROUND: To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2. METHODS: This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021. FINDINGS: ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference. INTERPRETATION: Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres. FUNDING: None.

Extracorporeal life support provision in COVID-19 patients - An international EuroELSO 2022 update survey.

INTRODUCTION: An analysis on the ECLS use for patients with respiratory or cardiac support in COVID-19 based on an international response to EuroELSO survey, aims to generate a more comprehensive understanding of ECLS role during the recent viral pandemic. METHODS: EuroELSO announced the survey at the 10th annual congress in London, May 2022. The survey covered 26 multiple-choice questions. RESULTS: The survey returned 69 questionnaires from 62 centers across 22 European countries and seven centers across five non-European countries. Most of the centers providing ECLS for COVID-19 patients had more than 30 runs for respiratory support since December 2019. In the same period, at least 31 runs in adult COVID-19 patients have been performed in 48 of 69 centers (69.6%). The reported pediatric data from 18 centers is limited to less than the patients per center. CONCLUSION: Majority of the COVID-19 patients received respiratory ECLS support and adult patients dominated. The indications and contraindications are broadly aligned with available guidelines. Most of the centers considered age >65 or biological age as a relative or absolute contraindication for ECLS in COVID-19. ECLS withdrawal criteria in COVID-19 are controversial because the long-term outcomes after ECLS in COVID-19 and the impact of critical illness and the impact of long-COVID are still not known.

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.

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients.

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection.

BACKGROUND: Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited understanding of the mechanistic pathways linked to post-acute pulmonary sequelae. AIM: To identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS. METHODS: Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO<60%) and age- and sex-matched individuals with mild-normal lung function (DLCO≥60%). A transcriptomic signature for optimal classification was constructed using random forest. Transcriptomic data were analyzed for biological pathway enrichment, cellular deconvolution, cell/tissue-specific gene expression and candidate drugs. RESULTS: RNA-seq identified 1357 differentially expressed transcripts. A model composed of 14 mRNAs allowed the optimal discrimination of survivors with severe diffusion impairment (AUC=0.979). Hallmarks of lung sequelae involved cell death signaling, cytoskeleton reorganization, cell growth and differentiation and the immune response. Resting natural killer (NK) cells were the most important immune cell subtype for the prediction of severe diffusion impairment. Components of the signature correlated with neutrophil, lymphocyte and monocyte counts. A variable expression profile of the transcripts was observed in lung cell subtypes and bodily tissues. One upregulated gene, TUBB4A, constitutes a target for FDA-approved drugs. CONCLUSIONS: This work defines the transcriptional programme associated with post-acute pulmonary sequelae and provides novel insights for targeted interventions and biomarker development.

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection.

Introduction: Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making. Aim: To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS. Methods: Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance. Results: After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-α were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1α, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a protein-based prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively. Conclusion: BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BAS-based protein testing emerges as a novel tool for risk assessment in the ICU.

Respiratory indications for ECMO: focus on COVID-19.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19.

Musicoterapia y telehealth: Una revisión sistemática

La crisis sanitaria y las restricciones provocadas por la COVID-19 han tenido un gran impacto en la salud física y mental con un incremento de la teleasistencia (telehealth). Se realiza una revisión sistemática de la literatura sobre la aplicación de la musicoterapia en telehealth en PsycInfo, PsicoDoc, Scopus, PubMed y Web of Science. Se identificaron 8 estudios que muestran mejoras en los objetivos terapéuticos y el uso de nuevos modelos de intervención y recursos tecnológicos. Se puede concluir que la investigación empírica en musicoterapia con telehealth es escasa, pero los estudios seleccionados abren un camino para su aplicación ante la dificultad de acceso a una terapia presencial. Alternate : La crisis sanitaria y las restricciones provocadas por la COVID-19 han tenido un gran impacto en la salud física y mental con un incremento de la teleasistencia (telehealth). Se realiza una revisión sistemática de la literatura sobre la aplicación de la musicoterapia en telehealth en PsycInfo, PsicoDoc, Scopus, PubMed y Web of Science. Se identificaron 8 estudios que muestran mejoras en los objetivos terapéuticos y el uso de nuevos modelos de intervención y recursos tecnológicos. Se puede concluir que la investigación empírica en musicoterapia con telehealth es escasa, pero los estudios seleccionados abren un camino para su aplicación ante la dificultad de acceso a una terapia presencial. Palabras clave: música;salud;musicoterapia;telehealth Destacados: La crisis sanitaria por COVID-19 ha provocado gran impacto en la salud física y mental. La musicoterapia vía telehealth puede ser una solución a las dificultades en disponibilidad de la terapia presencial.

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5–24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

PURPOSE: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. METHODS: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. RESULTS: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. CONCLUSION: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.

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.

Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS.

There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n = 167) and a group of infected patients who did not develop ARDS (n = 33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (DLCO) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. DLCO < 80% predicted was observed in 81.8% of the patients. TSS showed a median [P25;P75] of 5 [2;8]. The miRNA model associated with DLCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae.Trial registration: ClinicalTrials.gov identifier: NCT04457505..Trial registration: ISRCTN.org identifier: ISRCTN16865246..