Galactomannan-Antigen Testing from Non-Directed Bronchial Lavage for Rapid Detection of Invasive Pulmonary Aspergillosis in Critically Ill Patients: A Proof-of-Concept Study.

Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients' or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.

Secondary sclerosing cholangitis after COVID-19 pneumonia: a report of two cases and review of the literature.

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare disease characterized by chronic cholestasis. The underlying pathophysiology of SC-CIP is not fully understood, and prognosis in severe cases remains poor with liver transplantation remaining the only curative treatment option. There is a growing amount of literature describing patients with chronic cholangiopathy after COVID-19 infection. The vast majority of the patients described in these reports were male and had a poor outcome. While the exact percentage of patients with COVID-19-related SC-CIP cannot be estimated accurately due to a lack of larger studies, an increase in patients with long-term complications of chronic cholestatic liver disease after severe COVID19-pneumonia can be expected in the upcoming years. Treatment options remain limited and further research is needed to improve the dismal prognosis of SC-CIP. Here, we present the cases of two patients who developed SC-CIP after prolonged intensive care unit stay due to severe COVID-19 pneumonia. Both patients required invasive ventilation for 31 and 141 days, respectively, as well as extra-corporal membrane oxygenation for 23 and 87 days. The patients suffered from jaundice and severe pruritus, and typical features of SC-CIP were present by MRCP and ERC. Repeated removal of biliary casts resulted in some alleviation of their clinical symptoms, but cholestasis parameters remain elevated. Furthermore, an increased liver stiffness was indicative of advanced fibrosis in both patients. In addition to these two case reports, we provide a concise review of the literature of SC-CIP after COVID-19 infection and discuss risk factors, treatment options and prognosis.

Gut Microbial Disruption in Critically Ill Patients with COVID-19-Associated Pulmonary Aspergillosis.

OBJECTIVES: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). However, the causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a more complicated and severe disease course in COVID-19 patients, most likely due to immunological mechanisms. The aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbial composition. METHODS: We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potentially confounding influences on the microbiome during hospitalization. RESULTS: We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late-stage patients with CAPA superinfection exhibited an increased abundance of Staphylococcus epidermidis in the gut which was not found in late non-CAPA cases or early in the disease. The analysis of bronchial samples did not yield significant results. CONCLUSIONS: This is the first study showing that alterations in the gut microbiome accompany severe CAPA and possibly influence the host's immunological response. In particular, an increase in Staphylococcus epidermidis in the intestine could be of importance.

SARS-CoV-2 viral load dynamics in immunocompromised critically ill patients on remdesivir treatment.

The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long- COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 107 geq/ml (±33.25 x 107 geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 106 geq/ml (±6.93 x 106 geq/ml) on day 3 and to 1.4 x 105 geq/ml (±2.35 x 105 geq/ml) on day 5 of remdesivir treatment. Mean virus load dropped below <1% between day 1 and 5 of remdesivir treatment. Parent prodrug remdesivir and also GS441524 metabolite levels of antiviral activity in our patients were far in excess of EC 50. Our data present that remdesivir treatment potentially reduces the SARS-CoV-2 viral load in immunosuppressed critically ill patients. However, the implication of viral load reduction on morbidity and mortality needs further investigation.

Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders. METHODS: To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). RESULTS: In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. CONCLUSIONS: In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

Risk factors for Herpes simplex virus (HSV) and Cytomegalovirus (CMV) infections in critically-ill COVID-19 patients.

Background: To assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection. Methods: All mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohorts with and without HSV-1- infection. Results: 134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219). Conclusions: Our study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.

Risk factors for Herpes simplex virus (HSV) and Cytomegalovirus (CMV) infections in critically-ill COVID-19 patients

Background To assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection. Methods All mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohorts with and without HSV-1- infection. Results 134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219). Conclusions Our study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.

Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19.

There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.

Longitudinal Assessment of Health and Quality of Life of COVID-19 Patients Requiring Intensive Care-An Observational Study.

Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were prospectively followed-up at a median of 36, 75.5, 122 and 222 days after discharge. The health-related quality of life (HrQoL) (36-item Short Form Health Survey and St. George's Respiratory Questionnaire, SGRQ), cardiopulmonary function, laboratory parameters and chest imaging were assessed longitudinally. The HrQoL assessment revealed a reduced physical functioning, as well as increased SGRQ impact and symptoms scores that all improved over time but remained markedly impaired compared to the reference groups. The median radiological severity scores significantly declined; persistent abnormalities were found in 33.3% of the patients on follow-up. A reduced diffusion capacity was the most common abnormal pulmonary function parameter. The length of hospitalization correlated with role limitations due to physical problems, the SGRQ symptom and the impact score. In conclusion, in survivors of severe COVID-19, the pulmonary function and symptoms improve over time, but impairments in their physical function and diffusion capacity can persist over months. Longer follow-up studies with larger cohorts will be necessary to comprehensively characterize long-term sequelae upon severe COVID-19 and to identify patients at risk.

A Telemedicine-Guided Self-Collection Approach for PCR-Based SARS-CoV-2 Testing: Comparative Study.

BACKGROUND: Large-scale, polymerase chain reaction (PCR)-based SARS-CoV-2 testing is expensive, resource intensive, and time consuming. A self-collection approach is a probable alternative; however, its feasibility, cost, and ability to prevent infections need to be evaluated. OBJECTIVE: This study aims to compare an innovative self-collection approach with a regular SARS-CoV-2 testing strategy in a large European industrial manufacturing site. METHODS: The feasibility of a telemedicine-guided PCR-based self-collection approach was assessed for 150 employees (intervention group) and compared with a regular SARS-CoV-2 testing approach used for 143 employees (control group). Acceptance, ergonomics, and efficacy were evaluated using a software application. A simulation model was implemented to evaluate the effectiveness. An interactive R shiny app was created to enable customized simulations. RESULTS: The test results were successfully communicated to and interpreted without uncertainty by 76% (114/150) and 76.9% (110/143) of the participants in the intervention and control groups, respectively (P=.96). The ratings for acceptability, ergonomics, and efficacy among intervention group participants were noninferior when compared to those among control group participants (acceptability: 71.6% vs 37.6%; ergonomics: 88.1% vs 74.5%; efficacy: 86.4% vs 77.5%). The self-collection approach was found to be less time consuming (23 min vs 38 min; P<.001). The simulation model indicated that both testing approaches reduce the risk of infection, and the self-collection approach tends to be slightly less effective owing to its lower sensitivity. CONCLUSIONS: The self-collection approach for SARS-CoV-2 diagnosis was found to be technically feasible and well rated in terms of acceptance, ergonomics, and efficacy. The simulation model facilitates the evaluation of test effectiveness; nonetheless, considering context specificity, appropriate adaptation by companies is required.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

Dexamethasone therapy and rates of secondary pulmonary and bloodstream infections in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic. Bacterial superinfections seem to be associated with higher mortality in COVID-19 patients in intensive care units (ICUs). However, details on the prevalence and species distribution of secondary infections are limited. Moreover, the increasing use of dexamethasone may pose an additional risk of superinfections. METHODS: We performed a single-center retrospective study of the clinical and microbiological characteristics of 154 COVID-19 patients admitted to the ICU between March 2020 and January 2021, focusing on bacterial infections, use of antimicrobial agents and dexamethasone therapy. RESULTS: The median age was 68 years; 67.5% of the patients were men. Critically ill COVID-19 patients were treated with dexamethasone since July 2020 (second wave), which was not common during the first wave of the pandemic. In the dexamethasone group (n=90, 58.4%), respiratory pathogens were detected more frequently, as were multidrugresistant pathogens. The number of patients with polymicrobial detection of respiratory pathogens was significantly increased (p=0.013). The most frequently detected species were Enterobacterales, Staphylococcus aureus, and Aspergillus fumigatus. The rates of bloodstream infections did not differ between the groups. The use of dexamethasone in ICU COVID-19 patients was associated with higher rates of respiratory infectious complications. CONCLUSIONS: Secondary infections are present in a substantial fraction of critically ill COVID-19 patients. Respiratory pathogens were detectable in the majority of COVID-19 ICU patients. The use of dexamethasone poses a potential risk of secondary pulmonary infections. Infectious complications in patients with dexamethasone therapy could be associated with worse outcomes.

Convalescent plasma therapy in B-cell-depleted and B-cell sufficient patients with life-threatening COVID-19 - A case series.

OBJECTIVE: To investigate the effect of convalescent plasma therapy (CPT) on clinical courses of B-cell-sufficient and B-cell-depleted patients with life-threatening COVID-19. PATIENTS AND METHODS: In this case series, we retrospectively analysed clinical, laboratory and cardiopulmonary parameters of six patients with life-threatening COVID-19 receiving convalescent plasma (CP) as rescue therapy between April 11, 2020 to October 10, 2020. Clinical and laboratory parameters before and after transfusion were compared in two B-cell-depleted patients and four B-cell sufficient patients (control group). RESULTS: Both B-cell-depleted patients cleared SARS-CoV-2 virus and survived, while all other patients died within 14 days from intervention despite maximal therapeutic efforts. D-dimer levels increased in both cohorts subsequent to CPT. In control patients, mean Interleukin-6 increased and platelet levels decreased as opposed to decreasing and stable levels in B-cell-depleted patients, respectively. Control patients required increased doses of vasopressor compared to decreasing doses in B-cell depleted patients subsequent to CPT. PO2/FiO2 decrease was more pronounced and respiratory deterioration required postinterventional extracorporeal membrane oxygenation in two control patients. Transpulmonary thermodilution revealed a further increase of the Extravascular Lung Water Index upon CPT in control patients. CONCLUSION: Use of CP in late stages of life-threatening COVID-19 should be used with caution but may be beneficial in B-cell-depleted patients. Further studies are necessary to assess factors predicting potential therapeutic benefits as well as possible hazards.

Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.

PURPOSE: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure. METHODS: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire. RESULTS: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals. CONCLUSION: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.

Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany.

Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS.

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic.

BACKGROUND: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. METHODS: IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic's first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. RESULTS: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p < 0.01). Compared to hospitalized patients with a non-complicated course (non-ICU patients), seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p < 0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology > 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset. CONCLUSIONS: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2nd week following symptom onset.

Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study.

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.

High lipasemia is frequent in Covid-19 associated acute respiratory distress syndrome.

BACKGROUND: Covid-19 is a rapidly spreading viral disease that can cause severe acute respiratory distress syndrome (ARDS). Besides the lungs it can also affect other organs like the heart or the liver. Whether there is a pancreatic manifestation as well is currently unclear. METHODS: and aims: We prospectively collected patient information of patients with Covid-19 associated ARDS in a registry (COvid Registry REChts der Isar intensive care Trial - CORRECT) and analyzed this patient cohort for signs of acute pancreatitis (e.g. lipase activity >3 times the upper limit). RESULTS: 12/38 (31.6%) patients with Covid-19 associated ARDS had a serum lipase activity >180 U/l. Median lipase activity was 422 U/l (186-1127). No patient showed typical findings of acute pancreatitis on imaging studies. On hemodynamic monitoring no patient had signs of intravascular fluid demand regarding MAP, GEDVI and therapy with vasopressors. To avoid worsening respiratory function no treatment with crystalloids was initiated. Lipasemia was not explained by gastroenteritis or renal insufficiency, occurred before as well as after viral clearance and 16.1 ± 6.0 days after the first symptoms. No patient developed severe acute pancreatitis during the follow up period of 35.8 ± 8.3 days. CONCLUSION: High lipasemia without typical signs of acute pancreatitis is a frequent finding in severe Covid-19 associated ARDS. Considering the markedly high levels of serum lipase activity, we think impaired microcirculation in severely ill patients can explain this finding rather than extra-pancreatic co-morbidities (UTN: DRKS00021612).