Background: Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia. Methods: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls. Findings: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA. Interpretation: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.

The evolving dynamics of coronavirus disease 2019 (COVID-19) and the increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on polymerase chain reaction (PCR) testing. Two radiologists evaluated the severity of findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for ICU treatment. Patients with a severe course of COVID-19 had significantly increased interleukin (IL)-6, C-reactive protein (CRP), and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean ± standard deviation sensitivity, specificity and accuracy of 0.72 ± 0.1, 0.86 ± 0.16 and 0.80 ± 0.1 and a receiver operating characteristic-area under curve (ROC-AUC) of 0.79 ± 0.1. The need for ICU treatment is independently associated with affected lung volume, radiological severity score, CRP, and IL-6.

Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of cirrhosis‐associated immune dysfunction, humoral immunodeficiency, cell‐mediated dysfunction and systemic inflammation. Besides classical risk factors for invasive fungal infection, acute‐on‐chronic liver failure, corticosteroid use, gastrointestinal bleeding, and prophylactic use of antibiotics are all additional conditions which are related to the potential development of fungal infections. Therefore, high‐risk patients should be carefully followed by microbiological surveillance including cultures but also by imaging and fungal biomarkers for providing early diagnosis. Echinocandins are still the mainstay and first line antifungal therapy in cases of invasive candidiasis. Due to concerns of liver toxicity and in cases of renal impairment liposomal amphotericin B is a suitable alternative to voriconazole in patients with invasive pulmonary aspergillosis. Although, data of isavucoanzole and posaconazole use in those patients are also promising more specific studies in the subgroup of patients with liver impairment are needed. Especially, due to the late diagnosis and multiple organ dysfunction usually present in patients with liver impairment morbidity and mortality rates remain high. Based on the broad spectrum of diverse reports with varying content and quality and in some cases lack of evidence we performed a systematic review on this topic.

Acute-on-chronic liver failure (ACLF) is associated with high mortality. Objective prognostic scores are important for treatment decisions. EASIX (Endothelial Activation and Stress Index) is a simple biomarker consisting of LDH, platelets, and creatinine, reflecting endothelial dysfunction after allogeneic stem cell transplantation. Considering endothelial dysfunction in the pathogenesis of ACLF, this study aimed to test the discriminative ability of EASIX in advanced liver disease. We retrospectively analysed the prognostic potential of EASIX to predict 28-day and 3-month mortality in a total of 188 liver cirrhotic patients requiring treatment at the intensive care unit. We evaluated the ability of EASIX to rule out early infections and predict the need for hemodialysis. EASIX performed moderately better than established scores in predicting 28-day mortality (AUC = 0.771) and was nearly equivalent (AUC = 0.791) to SOFA and APACHE-II in the prediction of 3-month mortality. Importantly, EASIX showed better diagnostic potential in ruling out clinically apparent infections than common proinflammatory markers (AUC = 0.861, p < 0.001) and showed suitable accuracy in predicting the need for hemodialysis (AUC = 0.833). EASIX is an accurate, objective and easily assessable biomarker for predicting mortality and complications in patients with advanced liver disease.