Indications and results in cholestatic liver disease - PSC, SSC, PBC.

Primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and primary biliary cholangitis (PBC) are impor-tant indications for liver transplantation. An emerging indication for liver transplantation in selected cases is SSC after severe COVID-19 infection. The clinical presenta-tion of these cholestatic diseases is highly heterogeneous - from asymptomatic and mild elevations of liver enzymes to severe disease-specific complications like recurrent cholangitis or severe bone disorder to de-compensated liver cirrhosis. Such disease-specific clinical complications, disease-spe-cific scores, as well as the MELD score, need to be considered when selecting patients for liver transplantation.Copyright © 2023 Dustri-Verlag Dr. K. Feistle.

Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021

Background: Tracking person-to-person SARS-CoV-2 transmission in the population is important to under-stand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective. Aim: We demonstrate the successful appli-cation of the integrated genomic surveillance (IGS) system of the German city of Dusseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters. Methods: Genomic sur-veillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two geneti-cally defined clusters of SARS-CoV-2 isolates detected by IGS in Dusseldorf in July 2021. Results: Cluster 1 (n = 67 Dusseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Dusseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June;28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multi-ple independent introduction events of a viral strain circulating in Catalonia and other European coun-tries, followed by diffuse community transmission in Dusseldorf.

INCREASED PROTEASE-ACTIVATED RECEPTOR 1 AUTOANTIBODIES ARE ASSOCIATED with SEVERE COVID-19

Background: In acute COVID-19 infection, growing evidence hints towards a broad activation of plasma cells and the presence of pathologic autoantibodies (abs). A systematic screening for abs confrmed induction of diverse functional abs by SARS-CoV-2 infection (1, 2). Immune-mediated thrombosis, involving platelet activation, has been identifed as one of the key pathogenic mechanisms in COVID-19 and is linked to morbidity and mortality (3). As natural abs against G protein-coupled receptors, functional abs against the thrombin receptor type-1 (PAR-1) might predispose for increased activation of the coagulation system present in COVID-19 infection. Objectives: The aim of this study is to identify the diagnostic value of anti-PAR1 antibodies and their capacity to predict the outcome of COVID-19 infection. Methods: 82 serum samples from 55 individuals with COVID-19 derived from three different hospitals in Schleswig-Holstein, Germany, and 88 single time point samples from healthy controls were subjected to ELISA-based quantifcation of anti-PAR-1 abs (CellTrend GmbH Luckenwalde, Germany). The levels of anti-AT1R abs were compared with clinical and laboratory parameters. Results: COVID-19 patients revealed markedly increased levels of circulating anti-PAR1 abs in hospitalized patients particularly in those required intensive care treatment in comparison to controls (p < 0.0001, Figure 1a). Anti-PAR1 ab levels were highest in patients with fatal outcome (p = 0.006, Figure 1a). Receiver operating characteristic (ROC) analysis of PAR1 abs levels in COVID-19 patients revealed a sensitivity of 84.00% and a specifcity 79.25% for patients requiring intensive care unit (ICU) treatment and a sensitivity of 87.50 % and a specifcity 84.51 % to distinguish fatal vs. non-fatal disease outcome (Figure 1b). We found correlation of circulating anti-PAR1 abs with D dimers. Conclusion: The increased anti-PAR1 abs, their prediction to identify patients requiring ICU and fatal outcome, and the correlation with markers for blood clotting suggest a role for antibodies against PAR1 in the disease development of blood clotting in COVID-19.

SARS-CoV-2 antigen rapid tests For reliable detection of SARS-CoV-2 infection not suitable

Background. For detection of SARS-CoV-2-infected persons ("severe acute respiratory syndrome coronavirus 2") quantitative Real-Time PCR (qRT-PCR) remains the gold standard. SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) have the advantage of being fast and simple to use at any location. According to previous studies, Ag-RDTs seem to have poorer sensitivity and specificity. There are currently a few hundred Ag-RDTs available, but many of them have not been independently evaluated. Objectives. Evaluation of diagnostic performance of rapid antigen tests detecting SARS-CoV-2 from 6 different manufacturers. Materials and methods. We performed Ag-RDTS with naso- and oropharnygeal swabs from laboratory routine which had had already resulted in a positive qRT-PCR test. To exclude possible dilution effects when samples were used for a second time, we also performed qRT-PCR analytics for already used samples. The initially measured Ct values could be confirmed. Results. Ag-RDTs showed differences in discrimination between positive and negative results. In samples with lower virus concentrations (Ct value > 30), the results were not reliable and the discrimination between negative and positive results was not unambigious. Conclusions. Ag-RDTs with high sensitivity allow the identification of highly contagious patients anywhere. There are differences between manufacturers which are important when testing patients. An independent transparent evaluation of Ag-RDTs is necessary.

Predicting the potential for zoonotic transmission and host associations for novel viruses.

Host-virus associations have co-evolved under ecological and evolutionary selection pressures that shape cross-species transmission and spillover to humans. Observed virus-host associations provide relevant context for newly discovered wildlife viruses to assess knowledge gaps in host-range and estimate pathways for potential human infection. Using models to predict virus-host networks, we predicted the likelihood of humans as hosts for 513 newly discovered viruses detected by large-scale wildlife surveillance at high-risk animal-human interfaces in Africa, Asia, and Latin America. Predictions indicated that novel coronaviruses are likely to infect a greater number of host species than viruses from other families. Our models further characterize novel viruses through prioritization scores and directly inform surveillance targets to identify host ranges for newly discovered viruses.

STUDY OF SPREAD OF AEROSOLS DURING DIFFERENT BREATHING CYCLES USING COMPUTATIONAL FLUID DYNAMICS

With COVID-19 having spread so rapidly across the world, detailed physics of transmission of com- municable diseases must be understood to recommend effective preventive measures. Computational fluid dynamics can provide insights into the physics of transport of droplets. Droplets are not only emitted during sneezing and coughing, but also during normal activities such as breathing, speak- ing, and singing. In this paper, different breathing patterns and their effect on the spread of droplets of 1 micron size are studied. It has been found that long steady exhalations, as well as sinusoidal exhalations can cause the droplets to travel greater distances. Also, some observations of the effects of the inhalation cycle and its small region of influence are included in this work. © 2021 by Begell House, Inc.

Déterminants et impact pronostique de la dépense énergétique de repos des patients Covid-19 sous ventilation mécanique invasive en réanimation

Déclaration de liens d’intérêts: Les auteurs déclarent ne pas avoir de liens d’intérêts.

Evolution of the nutritional status of COVID-19 critically-ill patients: A prospective observational study from ICU admission to three months after ICU discharge.

BACKGROUND & AIMS: Malnutrition following intensive care unit (ICU) stay is frequent and could be especially prominent in critically ill Coronavirus Disease 2019 (COVID-19) patients as they present prolonged inflammatory state and long length stay. We aimed to determine the prevalence of malnutrition in critically ill COVID-19 patients both at the acute and recovery phases of infection. METHODS: We conducted a prospective observational study including critically ill COVID-19 patients requiring invasive mechanical ventilation discharged alive from a medical ICU of a university hospital. We collected demographic, anthropometric and ICU stay data (SAPS2, recourse to organ support and daily energy intake). Nutritional status and nutritional support were collected at one month after ICU discharge (M1) by phone interview and at 3 months after ICU discharge (M3) during a specialized and dedicated consultation conducted by a dietitian. Malnutrition diagnosis was based on weight loss and body mass index (BMI) criteria following the Global Leadership Initiative on Malnutrition. Primary outcome was the prevalence of malnutrition at M3 and secondary outcomes were the evolution of nutritional status from ICU admission to M3 and factors associated with malnutrition at M3. RESULTS: From march 13th to may 15th, 2020, 38 patients were discharged alive from the ICU, median [IQR] age 66 [59-72] years, BMI 27.8 [25.5-30.7] kg/m2 and SAPS2 47 [35-55]. Thirty-three (86%) patients were followed up to M3. Prevalence of malnutrition increased during the ICU stay, from 18% at ICU admission to 79% at ICU discharge and then decreased to 71% at M1 and 53% at M3. Severe malnutrition prevailed at ICU discharge with a prevalence of 55% decreasing 32% at M3. At M3, the only factors associated with malnutrition in univariate analysis were the length of invasive mechanical ventilation and length of ICU stay (28 [18-44] vs. 13 [11-24] days, P = 0.011 and 32 [22-48] vs. 17 [11-21] days, P = 0.006, respectively), while no ICU preadmission and admission factors, nor energy and protein intakes distinguished the two groups. Only 35% of undernourished patients at M3 had benefited from a nutritional support. CONCLUSION: Malnutrition is frequent, protracted and probably underrecognized among critically ill Covid-19 patients requiring invasive mechanical ventilation with more than half patients still being undernourished three months after ICU discharge. A particular attention should be paid to the nutritional status of these patients not only during their ICU stay but also following ICU discharge.