Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Die Rolle von inaktivem Rhomboid-Protein 2 (iRhom2) im akuten Myokardinfarkt

Purpose: Tumor necrosis factor-alpha (TNF-alpha) is released by immune cells in the course of acute myocardial infarction (AMI) and involved in impaired recovery of myocardial function and adverse cardiac remodeling. The interaction of recently discovered inactive rhomboid protein 2 (iRhom2) with the TNF-alpha converting enzyme (TACE) is required for proper shedding of soluble TNF-alpha from the cell surface of immune cells. We hypothesized that iRhom2 expression increases in monocytes of patients with AMI. Methods: Monocytes were MACS-sorted from peripheral blood from 50 patients with AMI (NSTEMI, n = 16; STEMI n = 34) at the day of admission (day 1) and 3 days after admission as well as from 50 patients with stable coronary artery disease (CAD), and 25 young and healthy volunteers as comparison groups. mRNA was isolated from sorted monocytes and expression levels of iRhom2, TACE and TNF-alpha were evaluated by real-time quantitative reverse transcription PCR (RT-qPCR). TNF-alpha protein levels were assessed in the serum. Levels of circulating classical, intermediate and non-classical monocyte subsets were determined by flow cytometry. Results: There was a significant increase of iRhom2 mRNA expression in monocytes and TNF-alpha levels in the serum at day 3 after AMI compared to day 1 (p=0.012 and p<0.001, respectively). Expression levels on day 3 were similar to those observed in patients with stable CAD. The increased iRhom2 expression in monocytes on day 3 was associated with increased levels of TACE mRNA expression (r=0.72, p<0.001), elevated serum TNF-alpha levels (r=0.33, p=0.019) and higher levels of circulating intermediate monocytes (r=0.37, p=0.009). Conclusions: Following AMI, iRhom2 expression in monocytes increases in parallel to TNF-alpha in the serum and levels of intermediate monocytes in the blood, reaching levels found in individuals with manifest CAD. These findings suggest that iRhom2 contributes to the potentially harmful inflammatory processes during AMI via regulation of TNF-alpha and may therefore serve as a potential therapeutic target.Hintergrund: Tumor-Nekrose-Faktor-alpha (TNF-alpha) wird infolge eines akuten Myokardinfarktes (AMI) vermehrt freigesetzt und spielt eine relevante Rolle bei der Entstehung von ungünstigen kardialen Remodeling im Verlauf. Die Interaktion zwischen dem vor kurzem bekannt gewordenen inaktiven Rhomboid-Protein 2 (iRhom2) und des TNF-alpha converting enzyme (TACE) ist essentiell für die Abspaltung von löslichem TNF-alpha von der Zelloberfläche myeloischer Zellen. Wir nehmen daher an, dass die mRNA-Expression von iRhom2 in Monozyten infolge eines AMI ansteigt. Methoden: Aus dem peripheren Blut von 50 Patienten mit AMI (NSTEMI, n = 16; STEMI, n = 34) wurden innerhalb von 24 Stunden (Tag 1) nach Krankenhausvorstellung sowie 3 Tage danach Monozyten mittels des MACS-Isolations-Kits isoliert. Anschließend wurde die mRNA der Monozyten extrahiert und die mRNA-Expression von iRhom2, TACE und TNF-alpha mit quantitativer Echtzeit-Reverse-Transkriptase-Polymerase-Kettenreaktion (RT-qPCR) quantifiziert. Zudem wurde an Tag 1 und Tag 3 nach AMI die TNF-alpha-Konzentration im Serum erhoben und die Monozyten-Subpopulationen mittels Durchflusszytometrie bestimmt. Als Vergleichsgruppen dienten 50 Patienten mit koronarer Herzerkrankung (KHK) sowie 25 junge, gesunde Probanden. Ergebnisse: Von Tag 1 zu Tag 3 nach AMI zeigte sich ein signifikanter Anstieg der mRNA-Expression von iRhom2 in Monozyten sowie der TNF-alpha-Konzentration im Serum (p = 0.012 bzw. p < 0.001). Das mRNA-Expressionsniveau an Tag 3 nach AMI war ähnlich dem von Patienten mit KHK. Die iRhom2-Expression in Monozyten war 3 Tage nach AMI positiv mit der mRNA-Expression von TACE (r = 0.72, p < 0.001), der Serum-TNF-alpha-Konzentration (r = 0.33, p = 0.019) und dem Anteil zirkulierender intermediärer Monozyten (r = 0.37, p = 0.009) assoziiert. Schlussfolgerung: Infolge eines AMI steigt die iRhom2-mRNA-Expression parallel zu der Serum-TNF-alpha-Konzentration und dem Anteil intermediärer Monozyten im Blut an und erreicht jeweils Level vergleichbar mit denen von Patienten mit manifester KHK. Diese Beobachtungen suggerieren, dass iRhom2 über die Modulation der TNF-alpha-Sekretion in myeloischen Zellen an den potentiell schädlichen inflammatorischen Prozessen nach einem AMI beteiligt ist und daher als neuartiges therapeutisches Target in Frage kommt

Changes in lignin and cellulose content during leaf litter decomposition in a Mediterranean ecosystem

The clinical utility of computational phenotyping for both genetic and rare diseases is increasingly appreciated; however, its true potential is yet to be fully realized. Alongside the growing clinical and research availability of sequencing technologies, precise deep and scalable phenotyping is required to serve unmet need in genetic and rare diseases. To improve the lives of individuals affected with rare diseases through deep phenotyping, global big data interrogation is necessary to aid our understanding of disease biology, assist diagnosis, and develop targeted treatment strategies. This includes the application of cutting-edge machine learning methods to image data. As with most digital tools employed in health care, there are ethical and data governance challenges associated with using identifiable personal image data. There are also risks with failing to deliver on the patient benefits of these new technologies, the biggest of which is posed by data siloing. The Minerva Initiative has been designed to enable the public good of deep phenotyping while mitigating these ethical risks. Its open structure, enabling collaboration and data sharing between individuals, clinicians, researchers and private enterprise, is key for delivering precision public health

Enabling Global Clinical Collaborations on Identifiable Patient Data: The Minerva Initiative

The clinical utility of computational phenotyping for both genetic and rare diseases is increasingly appreciated; however, its true potential is yet to be fully realized. Alongside the growing clinical and research availability of sequencing technologies, precise deep and scalable phenotyping is required to serve unmet need in genetic and rare diseases. To improve the lives of individuals affected with rare diseases through deep phenotyping, global big data interrogation is necessary to aid our understanding of disease biology, assist diagnosis, and develop targeted treatment strategies. This includes the application of cutting-edge machine learning methods to image data. As with most digital tools employed in health care, there are ethical and data governance challenges associated with using identifiable personal image data. There are also risks with failing to deliver on the patient benefits of these new technologies, the biggest of which is posed by data siloing. The Minerva Initiative has been designed to enable the public good of deep phenotyping while mitigating these ethical risks. Its open structure, enabling collaboration and data sharing between individuals, clinicians, researchers and private enterprise, is key for delivering precision public health.status: publishe

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose!#!Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course.!##!Methods!#!A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed.!##!Results!#!Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p &amp;lt; 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p &amp;lt; 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p &amp;lt; 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients.!##!Conclusions!#!Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19