[Noninvasive respiratory support and invasive ventilation in COVID­19 : Where do we stand today?] / Nichtinvasive respiratorische Unterstützung und invasive Beatmung bei COVID­19 : Wo stehen wir heute?

The controversy surrounding ventilation in coronavirus disease 2019 (COVID-19) continues. Early in the pandemic it was postulated that the high intensive care unit (ICU) mortality may have been due to too early intubation. As the pandemic progressed recommendations changed and the use of noninvasive respiratory support (NIRS) increased; however, this did not result in a clear reduction in ICU mortality. Furthermore, large studies on optimal ventilation in COVID-19 are lacking. This review article summarizes the pathophysiological basis, the current state of the science and the impact of different treatment modalities on the outcome. Potential factors that could undermine the benefits of noninvasive respiratory support are discussed. The authors attempt to provide guidance in answering the difficult question of when is the right time to intubate?

Nichtinvasive respiratorische Unterstützung und invasive Beatmung bei COVID‑19 : Wo stehen wir heute? Noninvasive respiratory support and invasive ventilation in COVID‑19Where do we stand today?

Die Kontroverse um das Thema Beatmung bei vorliegender „coronavirus disease 2019“ (COVID-19) hält an. Zu Beginn der Pandemie wurde postuliert, dass die hohe Letalität auf den Intensivstationen möglicherweise auf eine zu frühe Intubation zurückzuführen sei. Im Verlauf der Pandemie änderten sich die Empfehlungen der Fachgesellschaften, und die Häufigkeit der Anwendung von nichtinvasiver respiratorischer Unterstützung (NIRS) nahm zu. Weiterhin fehlen große Studien zur optimalen Beatmung von COVID-19-Patienten. Der vorliegende Übersichtsbeitrag fasst die pathophysiologischen Grundlagen, den aktuellen Stand der Wissenschaft und die Auswirkungen der unterschiedlichen Behandlungsmodalitäten auf das Outcome zusammen.

Duodenal tropism of SARS-CoV-2 and clinical findings in critically ill COVID-19 patients.

PURPOSE: Duodenal involvement in COVID-19 is poorly studied. Aim was to describe clinical and histopathological characteristics of critically ill COVID-19 patients suffering from severe duodenitis that causes a significant bleeding and/or gastrointestinal dysmotility. METHODS: In 51 critically ill patients suffering from SARS-CoV-2 pneumonia, severe upper intestinal bleeding and/or gastric feeding intolerance were indications for upper gastrointestinal endoscopy. Duodenitis was diagnosed according to macroscopic signs and mucosal biopsies. Immunohistochemistry was performed to detect viral specific protein and ACE2. In situ hybridization was applied to confirm viral replication. RESULTS: Nine of 51 critically ill patients (18%) suffering from SARS-CoV-2 pneumonia had developed upper GI bleeding complications and/or high gastric reflux. Five of them presented with minor and four (44%) with severe duodenitis. In two patients, erosions had caused severe gastrointestinal bleeding requiring PRBC transfusions. Immunohistochemical staining for SARS-CoV-2 spike protein was positive inside duodenal enterocytes in three of four patients suffering from severe duodenitis. Viral replication could be confirmed by in situ hybridization. CONCLUSION: Our data suggest that about 8% of critically ill COVID-19 patients may develop a severe duodenitis presumably associated with a direct infection of the duodenal enterocytes by SARS-CoV-2. Clinical consequences from severe bleeding and/or upper gastrointestinal dysmotility seem to be underestimated.

COVID-19 in Recent Lung Transplant Recipients: Clinical Outcomes and Management Strategies.

BACKGROUND: COVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation. METHODS: We describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes. RESULTS: Three of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma. CONCLUSIONS: COVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.

Sequential Organ Failure Assessment Outperforms Quantitative Chest CT Imaging Parameters for Mortality Prediction in COVID-19 ARDS.

(1) Background: Respiratory insufficiency with acute respiratory distress syndrome (ARDS) and multi-organ dysfunction leads to high mortality in COVID-19 patients. In times of limited intensive care unit (ICU) resources, chest CTs became an important tool for the assessment of lung involvement and for patient triage despite uncertainties about the predictive diagnostic value. This study evaluated chest CT-based imaging parameters for their potential to predict in-hospital mortality compared to clinical scores. (2) Methods: 89 COVID-19 ICU ARDS patients requiring mechanical ventilation or continuous positive airway pressure mask ventilation were included in this single center retrospective study. AI-based lung injury assessment and measurements indicating pulmonary hypertension (PA-to-AA ratio) on admission CT, oxygenation indices, lung compliance and sequential organ failure assessment (SOFA) scores on ICU admission were assessed for their diagnostic performance to predict in-hospital mortality. (3) Results: CT severity scores and PA-to-AA ratios were not significantly associated with in-hospital mortality, whereas the SOFA score showed a significant association (p < 0.001). In ROC analysis, the SOFA score resulted in an area under the curve (AUC) for in-hospital mortality of 0.74 (95%-CI 0.63-0.85), whereas CT severity scores (0.53, 95%-CI 0.40-0.67) and PA-to-AA ratios (0.46, 95%-CI 0.34-0.58) did not yield sufficient AUCs. These results were consistent for the subgroup of more critically ill patients with moderate and severe ARDS on admission (oxygenation index <200, n = 53) with an AUC for SOFA score of 0.77 (95%-CI 0.64-0.89), compared to 0.55 (95%-CI 0.39-0.72) for CT severity scores and 0.51 (95%-CI 0.35-0.67) for PA-to-AA ratios. (4) Conclusions: Severe COVID-19 disease is not limited to lung (vessel) injury but leads to a multi-organ involvement. The findings of this study suggest that risk stratification should not solely be based on chest CT parameters but needs to include multi-organ failure assessment for COVID-19 ICU ARDS patients for optimized future patient management and resource allocation.

CytoSorb® Hemoadsorption as a Promising Tool to Handle COVID-19-Induced Cytokine Storm.

Accumulating evidence suggests that a patient subgroup with severe COVID-19 develops a cytokine release syndrome leading to capillary leakage and organ injury. Recent publications addressing therapy of cytokine storms recommended new extracorporeal therapies such as hemoadsorption. This case report describes a 59-year-old SARS-CoV-2-positive patient with severe ARDS. Due to severe hyperinflammation with concomitant hemodynamic instability and progressive renal failure, combination of continuous renal replacement and CytoSorb® hemoadsorption therapy was initiated. Treatment resulted immediately in a control of the hyperinflammatory response. Simultaneously, lung function continued to improve accompanied by profound hemodynamic stabilization. We report the successful utilization of CytoSorb® hemoadsorption in the treatment of a patient with SARS-CoV-2-induced cytokine storm syndrome.

[Characteristics and outcome of 70 ventilated COVID-19 patients : Summary after the first wave at a university center]. / Charakteristika und Outcome von 70 beatmeten COVID-19-Patienten : Bilanz nach der ersten Welle an einem universitären Zentrum.

BACKGROUND: In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE: Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS: Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS: In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62 points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION: The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.

Risk Stratification for ECMO Requirement in COVID-19 ICU Patients Using Quantitative Imaging Features in CT Scans on Admission.

(1) Background: Extracorporeal membrane oxygenation (ECMO) therapy in intensive care units (ICUs) remains the last treatment option for Coronavirus disease 2019 (COVID-19) patients with severely affected lungs but is highly resource demanding. Early risk stratification for the need of ECMO therapy upon admission to the hospital using artificial intelligence (AI)-based computed tomography (CT) assessment and clinical scores is beneficial for patient assessment and resource management; (2) Methods: Retrospective single-center study with 95 confirmed COVID-19 patients admitted to the participating ICUs. Patients requiring ECMO therapy (n = 14) during ICU stay versus patients without ECMO treatment (n = 81) were evaluated for discriminative clinical prediction parameters and AI-based CT imaging features and their diagnostic potential to predict ECMO therapy. Reported patient data include clinical scores, AI-based CT findings and patient outcomes; (3) Results: Patients subsequently allocated to ECMO therapy had significantly higher sequential organ failure (SOFA) scores (p < 0.001) and significantly lower oxygenation indices on admission (p = 0.009) than patients with standard ICU therapy. The median time from hospital admission to ECMO placement was 1.4 days (IQR 0.2-4.0). The percentage of lung involvement on AI-based CT assessment on admission to the hospital was significantly higher in ECMO patients (p < 0.001). In binary logistic regression analyses for ECMO prediction including age, sex, body mass index (BMI), SOFA score on admission, lactate on admission and percentage of lung involvement on admission CTs, only SOFA score (OR 1.32, 95% CI 1.08-1.62) and lung involvement (OR 1.06, 95% CI 1.01-1.11) were significantly associated with subsequent ECMO allocation. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.83 (95% CI 0.73-0.94) for lung involvement on admission CT and 0.82 (95% CI 0.72-0.91) for SOFA scores on ICU admission. A combined parameter of SOFA on ICU admission and lung involvement on admission CT yielded an AUC of 0.91 (0.84-0.97) with a sensitivity of 0.93 and a specificity of 0.84 for ECMO prediction; (4) Conclusions: AI-based assessment of lung involvement on CT scans on admission to the hospital and SOFA scoring, especially if combined, can be used as risk stratification tools for subsequent requirement for ECMO therapy in patients with severe COVID-19 disease to improve resource management in ICU settings.

Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury.

PURPOSE: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. METHODS: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. RESULTS: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). CONCLUSION: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. TRIAL REGISTRATION: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Myocardial Inflammation and Dysfunction in COVID-19-Associated Myocardial Injury.

BACKGROUND: Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed. METHODS: We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy. RESULTS: Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%-60.5%) but moderately to severely reduced left ventricular global longitudinal strain of -11.2% (-7.6% to -15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (-11.2% [-9.2% to -14.7%] versus -15.6% [-12.5% to -19.6%] at follow-up; P=0.041). CONCLUSIONS: In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.

Prognostic Value of Admission Chest CT Findings for Invasive Ventilation Therapy in COVID-19 Pneumonia

(1) Background: To assess the value of chest CT imaging features of COVID-19 disease upon hospital admission for risk stratification of invasive ventilation (IV) versus no or non-invasive ventilation (non-IV) during hospital stay. (2) Methods: A retrospective single-center study was conducted including all patients admitted during the first three months of the pandemic at our hospital with PCR-confirmed COVID-19 disease and admission chest CT scans (n = 69). Using clinical information and CT imaging features, a 10-point ordinal risk score was developed and its diagnostic potential to differentiate a severe (IV-group) from a more moderate course (non-IV-group) of the disease was tested. (3) Results: Frequent imaging findings of COVID-19 pneumonia in both groups were ground glass opacities (91.3%), consolidations (53.6%) and crazy paving patterns (31.9%). Characteristics of later stages such as subpleural bands were observed significantly more often in the IV-group (52.2% versus 26.1%, p = 0.032). Using information directly accessible during a radiologist’s reporting, a simple risk score proved to reliably differentiate between IV- and non-IV-groups (AUC: 0.89 (95% CI 0.81–0.96), p <0.001). (4) Conclusions: Information accessible from admission CT scans can effectively and reliably be used in a scoring model to support risk stratification of COVID-19 patients to improve resource and allocation management of hospitals.

Liver transplantation in a patient after COVID-19 - Rapid loss of antibodies and prolonged viral RNA shedding.

To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA.

Attenuated early inflammatory response in solid organ recipients with COVID-19.

Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non-transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.