German Contributions to the 15th International Congress of Slavists, Minsk 2013

Der Sammelband enthält die 39 Beiträge der deutschen Teilnehmerinnen und Teilnehmer am 15. Internationalen Slavistenkongress, der vom 20.-27. August 2013 in Minsk stattfand.Beitr. teilw. dt., teilw. engl., teilw. franz., teilw. in kyrill. Schr., russ., teilw. in kyrill. Schr., weißruss.German Contributions to the 15th International Congress of Slavists, Minsk 2013. Comprises all 39 German papers (linguistics 31, literature 8). Published on behalf of the German Association of Slavists (Deutscher Slavistenverband)

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

Effects of pulmonary immunostimulation with MALP-2 on the course of secondary pneumococcal infection in influenza virus-infected mice

Sekundäre bakterielle Infektionen stellen eine bedeutende Komplikation der Infektion mit dem Influenza-A-Virus dar. Die Influenzavirusinfektion führt zu einer Schwächung der angeborenen Immunabwehr der Lunge und damit zu einer verringerten pulmonalen Erregerelimination. Häufigster Erreger der sekundären Pneumonie bei Influenza ist das Bakterium Streptococcus pneumoniae. Trotz moderner antibiotischer Therapie ist die Letalität der sekundären Pneumonie bei Influenza beträchtlich. Die lokale Stimulation des angeborenen Immunsystems der Lunge stellt eine neuartige Therapiestrategie dar, die auf die Aktivierung vorhandener Abwehrmechanismen des Organismus abzielt. Toll- like Rezeptoren (TLR) erkennen bestimmte, hochkonservierte Bestandteile von Pathogenen und führen zu einer Aktivierung des angeborenen Immunsystems. Das in dieser Arbeit verwendete Lipopeptid macrophage-activating lipopeptide of 2 kDa (MALP-2) ist ein spezifischer Agonist des TLR-2/6-Rezeptordimers. Ziel der vorliegenden Arbeit war die Untersuchung der Wirksamkeit einer lokalen Stimulation der pulmonalen Immunabwehr mit MALP-2 in der Prävention der sekundären Pneumokokkenpneumonie nach pulmonaler Vorschädigung durch Influenzavirusinfektion. Zur Analyse der Auswirkungen von MALP-2 auf eine vorbestehende Influenzavirusinfektion wurden weibliche C57BL/6 Mäuse transnasal mit dem Influenzavirus A/H1N1/PR/8/34 infiziert und 5 d später intratracheal mit MALP-2 behandelt. Die Applikation des MALP-2 induzierte eine Rekrutierung von Leukozyten in die Influenzavirus-infizierte Lunge mit Ausschüttung proinflammatorischer Zytokine. Die Auswirkungen der MALP-2-Stimulation blieben dabei auf die Lunge beschränkt und ohne Einfluss auf den Verlauf der viralen Infektion. Um den Effekt der MALP-2-Stimulation auf die sekundäre Pneumokokkenpneumonie zu untersuchen wurden Influenzavirus- infizierte Tiere mit S. pneumoniae transnasal infiziert. Durch die sekundäre bakterielle Infektion wandelte sich das histologische Bild der Virus-bedingten bronchointerstitiellen Pneumonie zu einer eitrigen Bronchopneumonie. Die pulmonale MALP-2 Behandlung der Influenzavirus-infizierten Tiere 24 h vor der S. pneumoniae-Infektion reduzierte die bakterielle Erregerlast in der Lunge und verbesserte die Überlebensrate bei sekundärer Pneumokokkenpneumonie. Die immunstimulatorische Behandlung mit MALP-2 führte jedoch nicht zu quantitativen Veränderungen in der Zytokinsekretion oder der Leukozytenrekrutierung in den bronchoalveolären Raum während der sekundären Pneumokokkenpneumonie. Es kam auch nicht zu einer überschießenden systemischen Entzündungsreaktion. Zusammenfassend zeigen die Ergebnisse der vorliegenden Arbeit eine Verbesserung der pulmonalen Immunabwehr bei Influenzavirusinfektion durch lokale Stimulation mit MALP-2 mit verbesserter Erregerelimination und gesteigerter Überlebensrate bei sekundärer Pneumokokkenpneumonie.Pulmonary infection with influenza virus is frequently complicated by secondary bacterial pneumonia. Influenza virus infection impairs the innate immune system resulting in reduced elimination of bacterial pathogens in the respiratory tract. The most prevalent pathogen inducing secondary pneumonia following primary influenza virus infection is Streptococcus pneumoniae. Despite potent antimicrobial therapy bacterial superinfection is still associated with a high case fatality rate. Local stimulation of the innate immune system in the lung is a novel strategy to prevent secondary bacterial infections by improving the host innate immune response. Specific molecular components of bacteria and other pathogens induce a local inflammatory reaction by activating Toll-like receptors of host cells. The macrophage- activating lipopeptide of 2 kDa (MALP-2) used in this study is a specific agonist for the TLR-2/6 receptor dimer. The objective of this study was to evaluate the effect of local stimulation of the pulmonary immune response with MALP-2 in influenza virus-infected mice on the course of secondary pneumococcal pneumonia. In a first set of experiments, female C57BL/6N mice were treated intratracheally with MALP-2 5 d after transnasal infection with influenza virus A/H1N1/PR/8/34 to study the effect of the pulmonary immuno- stimulation on the preexisting influenza virus infection. In influenza virus- infected mice, MALP-2 induced the release of proinflammatory cytokines and the recruitment of leukocytes into the bronchoalveolare space. The impact of the immuno-stimulation with MALP-2 was limited to the lung without any detectable systemic effects. Furthermore, no significant changes of the clinical parameters, the viral replication or the course of the influenza virus infection were observed. To study the impact of MALP-2 stimulation on secondary pneumococcal pneumonia, influenza virus-infected mice were transnasally infected with S. pneumoniae 24 h after intratracheal MALP-2 treatment. The bacterial superinfection caused purulent bronchopneumonia revealed by histopathological examination of the lung. In this model, MALP-2 treatment significantly reduced the bacterial burden of the lung and increased the survival rate after secondary pneumococcal infection. MALP-2 stimulation prior to secondary S. pneumoniae infection had, however, no effect on the local and systemic leukocyte recruitment and cytokine release. In conclusion, the results of this study indicate that local immunostimulation with the TLR2/6-agonist MALP-2 in influenza virus-infected mice prior to secondary pneumococcal superinfection improves bacterial elimination and increases survival

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