Managing the Next Wave of Influenza and/or SARS-CoV-2 in the ICU-Practical Recommendations from an Expert Group for CAPA/IAPA Patients.

The aim of this study was to establish practical recommendations for the diagnosis and treatment of influenza-associated invasive aspergillosis (IAPA) based on the available evidence and experience acquired in the management of patients with COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA/IAPA expert group defined 14 areas in which recommendations would be made. To search for evidence, the PICO strategy was used for both CAPA and IAPA in PubMed, using MeSH terms in combination with free text. Based on the results, each expert developed recommendations for two to three areas that they presented to the rest of the group in various meetings in order to reach consensus. As results, the practical recommendations for the management of CAPA/IAPA patients have been grouped into 12 sections. These recommendations are presented for both entities in the following situations: when to suspect fungal infection; what diagnostic methods are useful to diagnose these two entities; what treatment is recommended; what to do in case of resistance; drug interactions or determination of antifungal levels; how to monitor treatment effectiveness; what action to take in the event of treatment failure; the implications of concomitant corticosteroid administration; indications for the combined use of antifungals; when to withdraw treatment; what to do in case of positive cultures for Aspergillus spp. in a patient with severe viral pneumonia or Aspergillus colonization; and how to position antifungal prophylaxis in these patients. Available evidence to support the practical management of CAPA/IAPA patients is very scarce. Accumulated experience acquired in the management of CAPA patients can be very useful for the management of IAPA patients. The expert group presents eminently practical recommendations for the management of CAPA/IAPA patients.

Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. AIM: To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets. METHODS: A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors. RESULTS: A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them. CONCLUSION: Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.

Lung transplantation from controlled donation after circulatory death using simultaneous abdominal normothermic regional perfusion: A single center experience.

Despite the benefits of abdominal normothermic regional perfusion (A-NRP) for abdominal grafts in controlled donation after circulatory death (cDCD), there is limited information on the effect of A-NRP on the quality of the cDCD lungs. We aimed to study the effect of A-NRP in lungs obtained from cDCD and its impact on recipients´ outcomes. This is a study comparing outcomes of lung transplants (LT) from cDCD donors (September 2014 to December 2021) obtained using A-NRP as the abdominal preservation method. As controls, all lung recipients transplanted from donors after brain death (DBD) were considered. The primary outcomes were lung recipient 3-month, 1-year, and 5-year survival. A total of 269 LT were performed (60 cDCD and 209 DBD). There was no difference in survival at 3 months (98.3% cDCD vs. 93.7% DBD), 1 year (90.9% vs. 87.2%), and 5 years (68.7% vs. 69%). LT from the cDCD group had a higher rate of primary graft dysfunction grade 3 at 72 h (10% vs. 3.4%; p <  .001). This is the largest experience ever reported with the use of A-NRP combined with lung retrieval in cDCD donors. This combined method is safe for lung grafts presenting short-term survival outcomes equivalent to those transplanted through DBD.

Convalescent plasma treatment for patients of 80 years and older with COVID-19 pneumonia.

BACKGROUND: Older patients, frequently with multiple comorbidities, have a high mortality from COVID-19 infection. Convalescent plasma (CP) is a therapeutic option for these patients. Our objective is to retrospectively evaluate the efficacy and adverse events of CP treatment in this population group. METHODS: Forty one patients over 80 years old with COVID-19 pneumonia received CP added to standard treatment, 51.2% with high anti-SARS-CoV-2 IgG titers and 48.8% with low titers. Median time between the onset of symptoms and the infusion of plasma was 7 days (IQR 4-10). A similar group of 82 patients who received only standard treatment, during a period in which CP was not available, were selected as a control group. RESULTS: In-hospital mortality was 26.8% for controls and 14.6% for CP patients (P = 0.131) and ICU admission was 8.5% for controls and 4.9% for CP patients (P = 0.467). Mortality tended to be lower in the high-titer group (9.5%) than in the low-titer group (20%), and in patients transfused within the first 7 days of symptom onset (10%) than in patients transfused later (19.1%), although the differences were not statistically significant (P = 0.307 and P = 0.355 respectively). There was no difference in the length of hospitalization. No significant adverse events were associated with CP treatment. CONCLUSIONS: Convalescent plasma treatment in patients over 80 years old with COVID-19 pneumonia was well tolerated but did not present a statistically significant difference in hospital mortality, ICU admission, or length of hospitalization. The results should be interpreted with caution as only half the patients received high-titer CP and the small number of patients included in the study limits the statistical power to detect significant differences. TRIAL REGISTRATION: CEIm Cantabria # 2020.127.

Usefulness of the COVID-GRAM and CURB-65 scores for predicting severity in patients with COVID-19.

AIM: The aim of this study was to determine the usefulness of COVID-GRAM and CURB-65 scores as predictors of the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Caucasian patients. METHODS: This was a retrospective observational study including all adults with SARS-CoV-2 infection admitted to Hospital Universitario Marqués de Valdecilla from February to May 2020. Patients were stratified according to COVID-GRAM and CURB-65 scores as being at low-medium or high risk of critical illness. Univariate analysis, multivariate logistic regression models, receiver operating characteristic curve, and area under the curve (AUC) were calculated. RESULTS: A total of 523 patients were included (51.8% male, 48.2% female; mean age 65.63 years (standard deviation 17.89 years)), of whom 110 (21%) presented a critical illness (intensive care unit admission 10.3%, 30-day mortality 13.8%). According to the COVID-GRAM score, 122 (23.33%) patients were classified as high risk; 197 (37.7%) presented a CURB-65 score ≥2. A significantly greater proportion of patients with critical illness had a high COVID-GRAM score (64.5% vs 30.5%; P < 0.001). The COVID-GRAM score emerged as an independent predictor of critical illness (odds ratio 9.40, 95% confidence interval 5.51-16.04; P < 0.001), with an AUC of 0.779. A high COVID-GRAM score showed an AUC of 0.88 for the prediction of 30-day mortality, while a CURB-65 ≥2 showed an AUC of 0.83. CONCLUSIONS: The COVID-GRAM score may be a useful tool for evaluating the risk of critical illness in Caucasian patients with SARS-CoV-2 infection. The CURB-65 score could be considered as an alternative.

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.