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1.
Deutsches Arzteblatt International ; 118(47):A2212-A2216+A4, 2021.
Article in German | EMBASE | ID: covidwho-1865987
2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333728

ABSTRACT

BACKGROUND: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. METHOD: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. FINDINGS: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.2-1.6) and COVID-19 related mortality (HR 1.5, 95%CI 1.3-1.8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2.0, 95%CI 1.6-2.6), venous thromboembolism (OR 1.7, 95%CI 1.2-2.4), and hepatic injury (OR 1.6, 95%CI 1.2-2.0). Risk allele carriers <= 60 years had higher odds of death or severe respiratory failure (OR 2.6, 95%CI 1.8-3.9) compared to those > 60 years OR 1.5 (95%CI 1.3-1.9, interaction p-value=0.04). Amongst individuals <= 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31.8% (95%CI 27.6-36.2) were risk variant carriers, compared to 13.9% (95%CI 12.6-15.2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those <= 60 years improved when including the risk allele (AUC 0.82 vs 0.84, p=0.016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. INTERPRETATION: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals <= 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. FUNDING: Funding was obtained by each of the participating cohorts individually.

3.
Degenhardt, F.; Ellinghaus, D.; Juzenas, S.; Lerga-Jaso, J.; Wendorff, M.; Maya-Miles, D.; Uellendahl-Werth, F.; ElAbd, H.; Rühlemann, M. C.; Arora, J.; Özer, O.; Lenning, O. B.; Myhre, R.; Vadla, M. S.; Wacker, E. M.; Wienbrandt, L.; Ortiz, A. B.; de Salazar, A.; Chercoles, A. G.; Palom, A.; Ruiz, A.; Garcia-Fernandez, A. E.; Blanco-Grau, A.; Mantovani, A.; Zanella, A.; Holten, A. R.; Mayer, A.; Bandera, A.; Cherubini, A.; Protti, A.; Aghemo, A.; Gerussi, A.; Ramirez, A.; Braun, A.; Nebel, A.; Barreira, A.; Lleo, A.; Teles, A.; Kildal, A. B.; Biondi, A.; Caballero-Garralda, A.; Ganna, A.; Gori, A.; Glück, A.; Lind, A.; Tanck, A.; Hinney, A.; Nolla, A. C.; Fracanzani, A. L.; Peschuck, A.; Cavallero, A.; Dyrhol-Riise, A. M.; Ruello, A.; Julià, A.; Muscatello, A.; Pesenti, A.; Voza, A.; Rando-Segura, A.; Solier, A.; Schmidt, A.; Cortes, B.; Mateos, B.; Nafria-Jimenez, B.; Schaefer, B.; Jensen, B.; Bellinghausen, C.; Maj, C.; Ferrando, C.; de la Horra, C.; Quereda, C.; Skurk, C.; Thibeault, C.; Scollo, C.; Herr, C.; Spinner, C. D.; Gassner, C.; Lange, C.; Hu, C.; Paccapelo, C.; Lehmann, C.; Angelini, C.; Cappadona, C.; Azuure, C.; Bianco, C.; Cea, C.; Sancho, C.; Hoff, D. A. L.; Galimberti, D.; Prati, D.; Haschka, D.; Jiménez, D.; Pestaña, D.; Toapanta, D.; Muñiz-Diaz, E.; Azzolini, E.; Sandoval, E.; Binatti, E.; Scarpini, E.; Helbig, E. T.; Casalone, E.; Urrechaga, E.; Paraboschi, E. M.; Pontali, E.; Reverter, E.; Calderón, E. J.; Navas, E.; Solligård, E.; Contro, E.; Arana-Arri, E.; Aziz, F.; Garcia, F.; Sánchez, F. G.; Ceriotti, F.; Martinelli-Boneschi, F.; Peyvandi, F.; Kurth, F.; Blasi, F.; Malvestiti, F.; Medrano, F. J.; Mesonero, F.; Rodriguez-Frias, F.; Hanses, F.; Müller, F.; Hemmrich-Stanisak, G.; Bellani, G.; Grasselli, G.; Pezzoli, G.; Costantino, G.; Albano, G.; Cardamone, G.; Bellelli, G.; Citerio, G.; Foti, G.; Lamorte, G.; Matullo, G.; Baselli, G.; Kurihara, H.; Neb, H.; My, I.; Kurth, I.; Hernández, I.; Pink, I.; de Rojas, I.; Galván-Femenia, I.; Holter, J. C.; Afset, J. E.; Heyckendorf, J.; Kässens, J.; Damås, J. K.; Rybniker, J.; Altmüller, J.; Ampuero, J.; Martín, J.; Erdmann, J.; Banales, J. M.; Badia, J. R.; Dopazo, J.; Schneider, J.; Bergan, J.; Barretina, J.; Walter, J.; Quero, J. H.; Goikoetxea, J.; Delgado, J.; Guerrero, J. M.; Fazaal, J.; Kraft, J.; Schröder, J.; Risnes, K.; Banasik, K.; Müller, K. E.; Gaede, K. I.; Garcia-Etxebarria, K.; Tonby, K.; Heggelund, L.; Izquierdo-Sanchez, L.; Bettini, L. R.; Sumoy, L.; Sander, L. E.; Lippert, L. J.; Terranova, L.; Nkambule, L.; Knopp, L.; Gustad, L. T.; Garbarino, L.; Santoro, L.; Téllez, L.; Roade, L.; Ostadreza, M.; Intxausti, M.; Kogevinas, M.; Riveiro-Barciela, M.; Berger, M. M.; Schaefer, M.; Niemi, M. E. K.; Gutiérrez-Stampa, M. A.; Carrabba, M.; Figuera Basso, M. E.; Valsecchi, M. G.; Hernandez-Tejero, M.; Vehreschild, M. J. G. T.; Manunta, M.; Acosta-Herrera, M.; D'Angiò, M.; Baldini, M.; Cazzaniga, M.; Grimsrud, M. M.; Cornberg, M.; Nöthen, M. M.; Marquié, M.; Castoldi, M.; Cordioli, M.; Cecconi, M.; D'Amato, M.; Augustin, M.; Tomasi, M.; Boada, M.; Dreher, M.; Seilmaier, M. J.; Joannidis, M.; Wittig, M.; Mazzocco, M.; Ciccarelli, M.; Rodríguez-Gandía, M.; Bocciolone, M.; Miozzo, M.; Ayo, N. I.; Blay, N.; Chueca, N.; Montano, N.; Braun, N.; Ludwig, N.; Marx, N.; Martínez, N.; Cornely, O. A.; Witzke, O.; Palmieri, O.; Faverio, P.; Preatoni, P.; Bonfanti, P.; Omodei, P.; Tentorio, P.; Castro, P.; Rodrigues, P. M.; España, P. P.; Hoffmann, P.; Rosenstiel, P.; Schommers, P.; Suwalski, P.; de Pablo, R.; Ferrer, R.; Bals, R.; Gualtierotti, R.; Gallego-Durán, R.; Nieto, R.; Carpani, R.; Morilla, R.; Badalamenti, S.; Haider, S.; Ciesek, S.; May, S.; Bombace, S.; Marsal, S.; Pigazzini, S.; Klein, S.; Pelusi, S.; Wilfling, S.; Bosari, S.; Volland, S.; Brunak, S.; Raychaudhuri, S.; Schreiber, S.; Heilmann-Heimbach, S.; Aliberti, S.; Ripke, S.; Dudman, S.; Wesse, T.; Zheng, T.; Bahmer, T.; Eggermann, T.; Illig, T.; Brenner, T.; Pumarola, T.; Feldt, T.; Folseraas, T.; Cejudo, T. G.; Landmesser, U.; Protzer, U.; Hehr, U.; Rimoldi, V.; Monzani, V.; Skogen, V.; Keitel, V.; Kopfnagel, V.; Friaza, V.; Andrade, V.; Moreno, V.; Albrecht, W.; Peter, W.; Poller, W.; Farre, X.; Yi, X.; Wang, X.; Khodamoradi, Y.; Karadeniz, Z.; Latiano, A.; Goerg, S.; Bacher, P.; Koehler, P.; Tran, F.; Zoller, H.; Schulte, E. C.; Heidecker, B.; Ludwig, K. U.; Fernández, J.; Romero-Gómez, M.; Albillos, A.; Invernizzi, P.; Buti, M.; Duga, S.; Bujanda, L.; Hov, J. R.; Lenz, T. L.; Asselta, R.; de Cid, R.; Valenti, L.; Karlsen, T. H.; Cáceres, M.; Franke, A..
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-330452

ABSTRACT

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ~0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

4.
Sci Rep ; 11(1): 20143, 2021 10 11.
Article in English | MEDLINE | ID: covidwho-1462040

ABSTRACT

Rapid, high-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. While RT-PCR tests performed in centralized laboratories remain the gold standard, rapid point-of-care antigen tests might provide faster results. However, they are associated with markedly reduced sensitivity. Bedside breath gas analysis of volatile organic compounds detected by ion mobility spectrometry (IMS) may enable a quick and sensitive point-of-care testing alternative. In this proof-of-concept study, we investigated whether gas analysis by IMS can discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from other respiratory viruses in an experimental set-up. Repeated gas analyses of air samples collected from the headspace of virus-infected in vitro cultures were performed for 5 days. A three-step decision tree using the intensities of four spectrometry peaks correlating to unidentified volatile organic compounds allowed the correct classification of SARS-CoV-2, human coronavirus-NL63, and influenza A virus H1N1 without misassignment when the calculation was performed with data 3 days post infection. The forward selection assignment model allowed the identification of SARS-CoV-2 with high sensitivity and specificity, with only one of 231 measurements (0.43%) being misclassified. Thus, volatile organic compound analysis by IMS allows highly accurate differentiation of SARS-CoV-2 from other respiratory viruses in an experimental set-up, supporting further research and evaluation in clinical studies.


Subject(s)
Antigens, Viral/isolation & purification , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Animals , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/instrumentation , Chlorocebus aethiops , Coronavirus NL63, Human/immunology , Coronavirus NL63, Human/isolation & purification , Diagnosis, Differential , High-Throughput Screening Assays/instrumentation , High-Throughput Screening Assays/methods , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/isolation & purification , Ion Mobility Spectrometry , Proof of Concept Study , SARS-CoV-2/immunology , Vero Cells
6.
Med Klin Intensivmed Notfmed ; 117(4): 305-308, 2022 May.
Article in German | MEDLINE | ID: covidwho-1107747

ABSTRACT

BACKGROUND: In early 2020 the German healthcare system was put into a state of emergency due to the coronavirus disease 2019 (COVID-19) pandemic. Bavaria had to deal with more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections than any other German state during the first wave and currently has over 270,000 cases, accounting for about one fifth of all COVID-19 cases in Germany. The Bavarian Ministry of Interior together with the Bavarian Sate Ministry of Health and Care issued a general ruling at the beginning of the first wave that ordered the centralised organisation of hospital capacity, a redesign of the information technology (IT) management system and introduced reporting obligations for SARS-CoV-2/COVID-19. The goal of this analysis was to investigate the role that university hospitals played in the inpatient treatment of COVID-19 patients. METHODS: A retrospective evaluation of all inpatient COVID-19 cases that were reported through the "IVENA Sonderlage" (Ivena eHEALTH, [IVENA, interdisziplinärer Versorgungsnachweis, mainis IT-Service GmbH, Offenbach am Main, Germany]), a special module for the "Interdisciplinary Medical Care Capacity Management System" designed for extraordinary events and circumstances, was conducted by analysing the number of reported treatment days of all Bavarian hospitals that participated in the treatment of COVID-19 patients. RESULTS: During the first wave university hospitals provided relevant scientific contributions and played an important role in advising physicians, hospitals and politicians on the pandemic. In all, 20% of intensive care unit (ICU) and intermediate care (IMC) treatment days were provided by the university hospitals in particular for treatment of complex courses of COVID-19.

7.
Pneumologie ; 75(2): 88-112, 2021 Feb.
Article in German | MEDLINE | ID: covidwho-1033360

ABSTRACT

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Inpatients , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
8.
Notf Rett Med ; 24(6): 943-952, 2021.
Article in German | MEDLINE | ID: covidwho-648616

ABSTRACT

BACKGROUND: Since end of March, the health care system in Germany has been placed into a state of emergency in order to gain resources for the spreading coronavirus disease 2019 (COVID-19) pandemic. The overall goal of this study is to evaluate the number of emergency room patients at the time of the pandemic in order to draw conclusions about the influence of the COVID 19 pandemic on the number of patients in an emergency department. MATERIALS AND METHODS: With this descriptive epidemiologic study we collected and analyzed anonymized patient-related data of 19,357 cases presenting to the emergency department of the Klinikum rechts der Isar (Munich) from 01 February 2019 to 30 April 2019 and from 01 February 2020 to 30 April 2020. RESULTS: Despite an increase in the number of patients from 2019 to 2020, there was a significant drop in the number of emergencies from February to March 2020 and proceeding in April to a level below that of 2019. This was particularly observed in the field of trauma surgery, with a 40% decrease in the number of patients. With regard to the individual complaint patterns in March 2020, it was found that an increased incidence of malaise (+47%) and breathing problems (+36%) was recorded, whereas back pain (-41%), wounds (-29%), thoracic (-24%) and abdominal pain (-23%) were significantly less common than in the previous year. In terms of the severity of the complaints, the decline was mainly due to complaints with a low degree of urgency. CONCLUSION: In the course of the COVID-19 pandemic we observed a significant decline in the number of patients in one of the largest emergency rooms in Munich. This has to be avoided with existing hospital capacities, in order to prevent potential damage to health caused by postponed or missing emergency presentations.

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