Cerebral Autoregulation, Cerebral Hemodynamics, and Injury Biomarkers, in Patients with COVID-19 Treated with Veno-Venous Extracorporeal Membrane Oxygenation.

BACKGROUND: This study aimed to describe the cerebrovascular dynamics, in particular cerebral autoregulation (CA), and cerebral biomarkers as neuron-specific enolase (NSE) in patients with a diagnosis of coronavirus disease 2019 and acute respiratory distress syndrome as well as undergoing veno-venous extracorporeal membrane treatment. METHODS: This was a single center, observational study conducted in the intensive care unit of the University Hospital in Wroclaw from October 2020 to February 2022. Transcranial Doppler recordings of the middle cerebral artery conducted for at least 20 min were performed. Cerebral autoregulation (CA) was estimated by using the mean velocity index (Mxa), calculated as the moving correlation coefficient between slow-wave oscillations in cerebral blood flow velocity and arterial blood pressure. Altered CA was defined as a positive Mxa. Blood samples for the measurement of NSE were obtained at the same time as transcranial Doppler measurements. RESULTS: A total of 16 patients fulfilled the inclusion criteria and were enrolled in the study. The median age was 39 (34-56) years. Altered CA was found in 12 patients, and six out of seven patients who died had altered CA. A positive Mxa was a significant predictor of mortality, with a sensitivity of 85.7%. We found that three out of five patients with pathological changes in brain computed tomography and six out of ten patients with neurological complications had altered CA. NSE was a significant predictor of mortality (cutoff value: 28.9 µg/L); area under the curve = 0.83, p = 0.006), with a strong relationship between increased level of NSE and altered CA, χ2 = 6.24; p = 0.035; φ = 0.69. CONCLUSIONS: Patients with coronavirus disease 2019-related acute respiratory distress syndrome, requiring veno-venous extracorporeal membrane treatment, are likely to have elevated NSE levels and altered CA. The CA was associated with NSE values in this group. This preliminary analysis suggests that advanced neuromonitoring and evaluation of biomarkers should be considered in this population.

Intestinal Fatty Acid Binding Protein (I-FABP) as a Prognostic Marker in Critically Ill COVID-19 Patients.

Gastrointestinal symptoms are common in critically ill COVID-19 patients. There is currently no generally recognized method of assessing gastrointestinal injury in unconscious or sedated intensive care unit (ICU) patients. I-FABP (intestinal fatty acid binding protein) and citrulline have previously been studied as potential biomarkers of enterocyte damage in various gastrointestinal tract diseases, and changes in the levels of these markers may reflect intestinal wall damage in COVID-19. Patients with critical COVID-19, with diagnosed sepsis, or septic shock requiring ICU treatment were included in the study. Blood samples for citrulline and I-FABP were taken daily from day 1 to 5. I-FABP levels were significantly higher in patients who eventually died from COVID-19 than in survivors, and the optimal I-FABP cut-off point for predicting 28-day mortality was 668.57 pg/mL (sensitivity 0.739, specificity 0.765). Plasma levels of I-FABP, but not citrulline, were associated with significantly higher mortality and appeared to be a predictor of poor outcome in multivariate logistic regression analysis. In conclusion, I-FABP seems to be an effective prognostic marker in critically ill COVID-19 patients. Assessing mortality risk based on intestinal markers may be helpful in making clinical decisions regarding the management of intestinal injury, imaging diagnostics, and potential surgical interventions.

Inflammasome-related Markers upon ICU Admission do not Correlate with Outcome in Critically Ill COVID-19 Patients.

PURPOSE: The development of targeted biological therapies for coronavirus disease 2019 (COVID-19) requires reliable biomarkers that could help indicate how patients are responding. The hyperactivation of inflammasomes by the SARS-CoV2 virus is hypothesized to contribute to a more severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins upon admission to the intensive care unit (ICU). PATIENTS AND METHODS: We performed a prospective cohort study. Plasma samples were obtained from 45 critically ill COVID-19 patients and 10 patients without any signs of infection (traumatic brain injury [TBI]) on admission to the ICU. Concentrations of IL-1a, IL-1ß, IL-18, IL-1RA, galectin-1, apoptosis-associated speck-like proteins, LDH, ferritin, and gasdermin D were analyzed. A cell-free caspase-1 plasma assay was done by inhibitor-based immunoprecipitation followed by a Western Blot. Demographic and clinical characteristics were recorded. RESULTS: Inhospital mortality in COVID-19 patients was 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 pg/mL vs. 30764.20 pg/mL, P = 0.007), but other inflammasome-related biomarkers had similar concentrations. Patients with a Sequential Organ Failure Assessment (SOFA) score of > 9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison with low-risk patients (25551.3 pg/mL vs. 16302.7 pg/mL, P = 0.014; 14.5 pg/mL vs. 39.4pg/mL, P = 0.04, respectively). Statistically significant correlations were observed between: IL-1a and platelets (r = -0.37), IL-1 ß and platelets (r = -0.36), ferritin and INR (r = 0.39). Activated caspase-1 p35, whose presence was related to higher fibrinogen and lower D-dimers, was detected in 12 out of 22 COVID-19 patients and in none of the TBI patients. Moreover, densitometric analysis showed a significantly higher amount of p35 in patients with a SOFA score > 9. CONCLUSION: We found that the systemic markers of activation of inflammasomes in critically ill COVID-19 patients were not directly related to outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

Extracorporeal membrane oxygenation for severe COVID-19-associated acute respiratory distress syndrome in Poland: a multicenter cohort study.

BACKGROUND: In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. METHODS: This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. RESULTS: There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). CONCLUSIONS: The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.

Influenza in patients with respiratory failure admitted to intensive care units in Poland and the use of extracorporeal respiratory support: a survey-based multicenter study.

BACKGROUND: In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support. METHODS: This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn-winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated. RESULTS: Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU. CONCLUSION: A substantial number of influenza infections occurred in the autumn-winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.

Immunosuppression as a Hallmark of Critical COVID-19: Prospective Study.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/ß and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/ß and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.