TRAIL und IP-10 als Prädiktor für die Verlaufsschwere einer COVID-19 Infektion auf Intensivstation

Hintergrund und Ziele Die Vorhersage der Verlaufsschwere einer COVID-19 Infektion mittels Biomarkern wie interferon-gamma-induced-protein (IP-10) und TNF-related-apoptosis-inducing-ligand (TRAIL) könnte ein hilfreiches Mittel sein um Risikopatienten zu detektieren und ggf. frühzeitig einer Therapie z.B: mit monoklonalen Antikörpern zukommen zu lassen. Andererseits könnten unnötige Therapien verhindert und damit Ressourcen gespart werden. Methoden In dieser prospektiven Studie wurde der Serumspiegel von TRAIL und IP-10 gemessen und deren Korrelation mit Verlaufsschwere („Beatmungsdauer“, „ICU Behandlungstage“ und „Krankenhaustage“, „ECMO Therapie“ vs. „non ECMO“) und Outcome („Versterben“ vs. „ICU Entlassung“) der Patienten untersucht. Außerdem wurde die Korrelation der beiden Biomarker mit dem SAPS II Score betrachtet. Ergebnisse Insgesamt wurden 365 Messungen bei 22 Intensivpatienten (mittleres Alter 63,5, 13,6 % weiblich) der ersten COVID-19 Welle von März 2020 bis Mai 2020 durchgeführt. Relevante signifikante Korrelationen bestanden für IP-10 Werte und dem Endpunkt „verstorben“ (IP-10 Initialwert p= 0,003 / IP-10 Mittelwert p=0,002 / IP-10 Maximalwertmessung p <0,001), sowie signifikante starke Korrelation der TRAIL Werte mit „Beatmungsdauer“, „ICU Therapietage“ und der „Krankenhausverweildauer“ (Beatmungstage: TRAIL Initialwert (Spearman -0,562, p 0,037) TRAIL Mittelwert (Spearman -0,597, p<0,024) TRAIL Minimalwertmessung(Spearman -0,786, p<0,001), ICU Therapietage: TRAIL Initialwert (Spearman -0,598, p<0,024) TRAIL Mittelwert (Spearman -0,607, p<0,021) TRAIL Minimalwertmessung (Spearman -0,790, p<0,001), Krankenhausverweildauer: TRAIL Initialwert (Spearman -0,606, p<0,022) TRAIL Mittelwert (Spearman -0,657, p<0,011) TRAIL Minimalwertmessung (Spearman -0,780, p<0,001). TRAIL korrelierte moderat (Spearman -0,367, p<0,001) und IP-10 schwach (Spearman -0,1,88, p<0,001). mit den SAPS II Werten. Schlussfolgerung Unter Berücksichtigung der erheblichen Limitationen der Studie zeigt sich IP-10, wie auch schon in anderen Studien gezeigt, als möglicher Prädiktor eines schlechten Outcomes einer COVID-19 Infektion. TRAIL erweist sich wiederum als möglicher Prädiktor der Infektionsverlaufsschwere („Beatmungsdauer“, „ICU Therapiedauer“ und „Krankenhausverweildauer“). Beide Biomarker korrelieren mit dem vorhergesagten Mortalitätsrisiko durch den SAPS II Score.TRAIL and IP-10 as predictors of course severity a COVID-19 infection in intensive care unit Abstract Predicting the severity of COVID-19 infection using biomarkers such as interferon-gamma-induced protein (IP-10) and TNF-related-apoptosis-inducing-ligand (TRAIL) could be a helpful means of detecting high-risk patients and, if necessary, providing them with therapy e.B: with monoclonal antibodies at an early stage. On the other hand, unnecessary therapies could be prevented and resources saved. Methods In this prospective study, serum levels of TRAIL and IP-10 were measured and their correlation with patient severity („duration of ventilation“, „ICU treatment days“ and „hospital days“, „ECMO therapy“ versus „non-ECMO“) and outcome („death“ vs. „ICU discharge“) of patients was investigated. In addition, the correlation of the two biomarkers with the SAPS II Score was considered. Results A total of 365 measurements were taken on 22 intensive care patients (mean age 63.5, 13.6% female) of the first COVID-19 wave from March 2020 to May 2020. Relevant significant correlations existed for IP-10 values and the endpoint „deceased“ (IP-10 initial value p= 0.003 / IP-10 mean p=0.002 / IP-10 maximum value measurement p <0.001), as well as significant strong correlation of TRAIL values with „ventilation duration“, „ICU therapy days“ and „hospital length of stay“ (Ventilation days: TRAIL initial value (Spearman -0.562, p 0.037) TRAIL mean value (Spearman -0.597, p<0.024) TRAIL minimum value measurement (Spearman -0.786, p<0.001), ICU therapy days: TRAIL initial value (Spearman -0.598, p<0.024) TRAIL mean value (Spearman -0.607, p<0.021) TRAIL minimum value measurement (Spearman -0.790, p<0.001), Hospital length: TRAIL initial value (Spearman -0.606, p<0.022) TRAIL mean value (Spearman -0.657, p<0.011) TRAIL minimum value measurement (Spearman -0.780, p<0.001). TRAIL correlated moderately (Spearman -0.367, p<0.001) and IP-10 weak (Spearman -0.1.88, p<0.001). with the SAPS II values. Conclusions Taking into account the considerable limitations of the study, IP-10, as already shown in other studies, is a possible predictor of a poor outcome of a COVID-19 infection. TRAIL, in turn, as a predictor of the severity of the course of infection („duration of ventilation“, „ICU duration of therapy“ and „length of hospital stay“). Both biomarkers correlate with the predicted mortality risk from the SAPS II Score.

Comparison of isoflurane and propofol sedation in critically ill COVID-19 patients-a retrospective chart review

Purpose In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome). Methods Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded. Results Patients’ age (median [interquartile range]) was 64 (60–68) years. They were invasively ventilated for 36 [21–50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h−1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour−1∙kg−1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720–960] versus 1080 [720–1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (− 4.0 [− 4.0 to − 3.0] versus − 3.0 [− 3.6 to − 2.5]; p < 0.01). Conclusion Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients

Acute Respiratory Distress Syndrome due to Mycoplasma pneumoniae Misinterpreted as SARS-CoV-2 Infection

Background. In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. Conclusion. Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS

Plasma Metabolome Alterations Discriminate between COVID-19 and Non-COVID-19 Pneumonia

Pneumonia is a common cause of morbidity and mortality and is most often caused by bacterial pathogens. COVID-19 is characterized by lung infection with potential progressive organ failure. The systemic consequences of both disease on the systemic blood metabolome are not fully understood. The aim of this study was to compare the blood metabolome of both diseases and we hypothesize that plasma metabolomics may help to identify the systemic effects of these diseases. Therefore, we profiled the plasma metabolome of 43 cases of COVID-19 pneumonia, 23 cases of non-COVID-19 pneumonia, and 26 controls using a non-targeted approach. Metabolic alterations differentiating the three groups were detected, with specific metabolic changes distinguishing the two types of pneumonia groups. A comparison of venous and arterial blood plasma samples from the same subjects revealed the distinct metabolic effects of pulmonary pneumonia. In addition, a machine learning signature of four metabolites was predictive of the disease outcome of COVID-19 subjects with an area under the curve (AUC) of 86 ± 10 %. Overall, the results of this study uncover systemic metabolic changes that could be linked to the etiology of COVID-19 pneumonia and nonCOVID-19 pneumonia

Respiratory Physiology of COVID-19 and Influenza Associated Acute Respiratory Distress Syndrome

There is ongoing debate whether lung physiology of COVID-19-associated acute respiratory distress syndrome (ARDS) differs from ARDS of other origin. Objective: The aim of this study was to analyze and compare how critically ill patients with COVID-19 and Influenza A or B were ventilated in our tertiary care center with or without extracorporeal membrane oxygenation (ECMO). We ask if acute lung failure due to COVID-19 requires different intensive care management compared to conventional ARDS. Methods: 25 patients with COVID-19-associated ARDS were matched to a cohort of 25 Influenza patients treated in our center from 2011 to 2021. Subgroup analysis addressed whether patients on ECMO received different mechanical ventilation than patients without extracorporeal support. Results: Compared to Influenza-associated ARDS, COVID-19 patients had higher ventilatory system compliance (40.7 mL/mbar [31.8–46.7 mL/mbar] vs. 31.4 mL/mbar [13.7–42.8 mL/mbar], p = 0.198), higher ventilatory ratio (1.57 [1.31–1.84] vs. 0.91 [0.44–1.38], p = 0.006) and higher minute ventilation at the time of intubation (mean minute ventilation 10.7 L/min [7.2–12.2 L/min] for COVID-19 vs. 6.0 L/min [2.5–10.1 L/min] for Influenza, p = 0.013). There were no measurable differences in P/F ratio, positive end-expiratory pressure (PEEP) and driving pressures (∆P). Respiratory system compliance deteriorated considerably in COVID-19 patients on ECMO during 2 weeks of mechanical ventilation (Crs, mean decrease over 2 weeks −23.87 mL/mbar ± 32.94 mL/mbar, p = 0.037) but not in ventilated Influenza patients on ECMO and less so in ventilated COVID-19 patients without ECMO. For COVID-19 patients, low driving pressures on ECMO were strongly correlated to a decline in compliance after 2 weeks (Pearson’s R 0.80, p = 0.058). Overall mortality was insignificantly lower for COVID-19 patients compared to Influenza patients (40% vs. 48%, p = 0.31). Outcome was insignificantly worse for patients requiring veno-venous ECMO in both groups (50% mortality for COVID-19 on ECMO vs. 27% without ECMO, p = 0.30/56% vs. 34% mortality for Influenza A/B with and without ECMO, p = 0.31). Conclusion: The pathophysiology of early COVID-19-associated ARDS differs from Influenza-associated acute lung failure by sustained respiratory mechanics during the early phase of ventilation. We question whether intubated COVID-19 patients on ECMO benefit from extremely low driving pressures, as this appears to accelerate derecruitment and consecutive loss of ventilatory system compliance

Killer immunoglobulin-like receptor 2DS5 is associated with recovery from coronavirus disease 2019

Background Despite numerous advances in the identification of risk factors for the development of severe coronavirus disease 2019 (COVID-19), factors that promote recovery from COVID-19 remain unknown. Natural killer (NK) cells provide innate immune defense against viral infections and are known to be activated during moderate and severe COVID-19. Killer immunoglobulin-like receptors (KIR) mediate NK cell cytotoxicity through recognition of an altered MHC-I expression on infected target cells. However, the influence of KIR genotype on outcome of patients with COVID-19 has not been investigated so far. We retrospectively analyzed the outcome associations of NK cell count and KIR genotype of patients with COVID-19 related severe ARDS treated on our tertiary intensive care unit (ICU) between February and June 2020 and validated our findings in an independent validation cohort of patients with moderate COVID-19 admitted to our tertiary medical center. Results Median age of all patients in the discovery cohort (n = 16) was 61 years (range 50–71 years). All patients received invasive mechanical ventilation; 11 patients (68%) required extracorporeal membrane oxygenation (ECMO). Patients who recovered from COVID-19 had significantly higher median NK cell counts during the whole observational period compared to patients who died (121 cells/µL, range 16–602 cells/µL vs 81 cells/µL, range 6–227 cells/µL, p-value = 0.01). KIR2DS5 positivity was significantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p-value = 0.01). KIR2DS5 positivity was significantly associated with freedom from transfer to ICU (0% vs 9%, p-value = 0.04) in the validation cohort which consisted of 65 patients with moderate COVID-19. Conclusion NK cells and KIR genotype might have an impact on recovery from COVID-19

TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection : a prospective cohort study

Background: Early prognostication of COVID-19 severity will potentially improve patient care. Biomarkers, such as TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10), and C-reactive protein (CRP), might represent possible tools for point-of-care testing and severity prediction. Methods: In this prospective cohort study, we analyzed serum levels of TRAIL, IP-10, and CRP in patients with COVID-19, compared them with control subjects, and investigated the association with disease sever ity. Results: A total of 899 measurements were performed in 132 patients (mean age 64 years, 40.2% females). Among patients with COVID-19, TRAIL levels were lower (49.5 vs 87 pg/ml, P = 0.0142), whereas IP-10 and CRP showed higher levels (667.5 vs 127 pg/ml, P <0.001; 75.3 vs 1.6 mg/l, P <0.001) than healthy controls. TRAIL yielded an inverse correlation with length of hospital and intensive care unit (ICU) stay, Simplified Acute Physiology Score II, and National Early Warning Score, and IP-10 showed a positive cor relation with disease severity. Multivariable regression revealed that obesity (adjusted odds ratio [aOR] 5.434, 95% confidence interval [CI] 1.005-29.38), CRP (aOR 1.014, 95% CI 1.002-1.027), and peak IP-10 (aOR 1.001, 95% CI 1.00-1.002) were independent predictors of in-ICU mortality

Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation

Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival

Comparison of immersive and non-immersive virtual reality videos as substitute for in-hospital teaching during coronavirus lockdown: a survey with graduate medical students in Germany

As a consequence of the continued Covid-19 lockdown in Germany, in-hospital teaching for medical students was impossible. While lectures and other theoretical training were relatively easily converted into online sessions using platforms such as Moodle, Zoom and Microsoft Teams, this was not the case for practical skills and clinical interventions, such as bronchoscopy or colonoscopy. This study describes a workaround that was implemented at the Saarland University Hospital utilizing virtual reality equipment to convey the impressions of shadowing clinical procedures to the students without physical presence. To achieve this, 3D 180° videos of key clinical interventions of various internal medicine specialities were recorded, cut, and censored. The videos were uploaded to the e-learning YouTube channel of our institution and shared with the students via the private share function. The students could choose whether to use a VR-viewer to watch the videos immersively or to watch them without a viewer on a screen non-immersively. At the end of the course after 1 week, the students completed a questionnaire anonymously focusing on learning-success regarding the presented topics, a self-assessment, and an evaluation of the course. A total of 27 students watched the videos with a VR-Viewer and 74 watched non-immersively. Although the VR-viewer group self-assessed their expertise higher, there was no significant difference between the two groups in the learning-success test score. However, students in the VR-viewer group rated the learning atmosphere, comprehensibility, and overall recommendation of the course significantly higher. They also agreed significantly more to the statement, that they gained a better conception of the presented procedures, and that virtual reality might be an appropriate tool for online teaching. Video-assisted teaching facilitates learning and might be a valuable add-on to conventional teaching.Abbreviations: Covid-19: severe acute respiratory syndrome coronavirus 2; 3D: three-dimensional; 2D: Two-dimensional; VR: virtual realit