Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming

Rationale Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis;however, its function in the host response to viral infections during sepsis remains elusive. Objectives To investigate the role of IL-3 during viral pneumonia in sepsis. Methods We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). Measurements and main results Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. Conclusion Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs.

Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming.

Rationale: Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. Objectives: To investigate the role of IL-3 during viral pneumonia in sepsis. Methods: We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). Measurements and main results: Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. Conclusion: Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs.

Collateral effects of the SARS-CoV-2 pandemic on oncologic surgery in Bavaria.

BACKGROUND: The ongoing SARS-COV-2 pandemic has severe implications for people and healthcare systems everywhere. In Germany, worry about the consequences of the pandemic led to the deferral of non-emergency surgeries. Tumor surgery accounts for a large volume in the field of visceral surgery and cannot be considered purely elective. It is not known how the SARS-COV-2 pandemic has changed the surgical volume in tumor patients. METHODS: Retrospective analysis of the amount of oncological surgeries in three academic visceral surgery departments in Bavaria, Germany, in 2020. Procedures were split into subgroups: Upper Gastrointestinal (Upper GI), Colorectal, Hepato-Pancreato-Biliary (HPB), Peritoneal and Endocrine. Procedures in 2020 were compared to a reference period from January 1st, 2017 to December 31st 2019. Surgical volume was graphically merged with SARS-COV-2 incidence and the number of occupied ICU beds. RESULTS: Surgical volume decreased by 7.6% from an average of 924 oncologic surgeries from 2017 to 2019 to 854 in 2020. The decline was temporally associated with the incidence of infections and ICU capacity. Surgical volume did not uniformly increase to pre-pandemic levels in the months following the first pandemic wave with lower SARS-COV-2 incidence and varied according to local incidence levels. The decline was most pronounced in colorectal surgery where procedures declined on average by 26% following the beginning of the pandemic situation. CONCLUSION: The comparison with pre-pandemic years showed a decline in oncologic surgeries in 2020, which could have an impact on lost life years in non-COVID-19 patients. This decline was very different in subgroups which could not be solely explained by the pandemic.

[Economic impact of the COVID-19 pandemic in general and visceral surgery : A comparison of performance and revenue data from two departments of hospitals with different levels of referral]. / Ökonomische Auswirkung der COVID-19-Pandemie in der Allgemein- und Viszeralchirurgie : Ein Vergleich von Leistungs- und Erlösdaten zweier Kliniken aus Krankenhäusern unterschiedlicher Versorgungsstufen.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, German hospitals were required to limit the capacity for elective surgery to prevent the healthcare system from general overload. In March 2020, the German government passed the COVID-19 Hospital Relief Act that guaranteed compensation payments for these limitations. In this study the regional impact of this intervention were analyzed. MATERIAL AND METHODS: The performance data and revenue figures for the departments of general and visceral surgery of the University Hospital of Erlangen (UKER) and the District Hospital St. Anna Höchstadt/Aisch (KKH) during the period from 1 April to 30 June 2019 were compared with the respective period in 2020. RESULTS: There was a significant decrease in bed occupancy rates and case numbers of inpatient treatment. The latter declined by 20.06% in the UKER and 60.76% in the KKH. Nononcological elective surgery was reduced by 33.04% in the UKER and 60.87% in the KKH. The number of emergency procedures remained unchanged in the UKER, while they decreased by 51.58% in the KKH. The revenues from diagnosis-related groups (DRG) decreased by 22.12% (UKER) and 54% (KKH), respectively. After taking compensation payments and savings from variable material costs into account, the UKER recorded a loss of -3.87%, while there was a positive revenue effect of 6.5% in the KKH. DISCUSSION: The nonselective restriction of elective surgery had a significant impact on patient care and revenue figures at both locations. With respect to the increase of intensive care capacities, such untargeted measures do not appear to be efficient. In addition, the fixed rate of compensation payments led to an unbalanced distribution of the financial aid between the two departments.

Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.

Oncological colorectal surgery during the COVID-19pandemic-a national survey.

PURPOSE: The aim of this study was to clarify the surgical supply situation of oncological colorectal patients in Germany during limitations of the OR caseload due to the COVID-19 pandemic. METHODS: Between 11th and 19th April 2020, all members of a consortium of German colorectal cancer centers were invited to participate in a web-based survey on the current status of surgical care situation of colorectal cancer patients in Germany. RESULTS: A total of 112 colorectal surgeons of 101 German hospitals participated in the survey. Eighty-seven percent of the participating hospitals had to reduce their total surgical caseload and 34% their surgical volume for oncological colorectal patients during COVID-19 pandemic. Restrictions of the surgical caseload were independent of the size of the hospital and the number of cases of COVID-19 in the federal state of the hospital. Sixteen percent of colorectal surgeons consider surgical limitations to be not justified and 78% to be justified only if the care of oncological patients is ensured. Ninety-five percent of the colorectal surgeons interviewed stated that all oncological colorectal patients with an indication for surgery should be operated in time, despite the current reservations for COVID-19 patients. For the majority of the respondents (63% and 51%, respectively), an extended waiting time for surgery of up to 2 weeks was acceptable for non-metastatic and metastatic patients, respectively. CONCLUSION: In Germany, there is a temporarily relevant reduction of surgical volume in oncological colorectal patients. Most colorectal surgeons stated that oncological colorectal surgery should not be compromised despite the measures taken during the COVID-19 pandemic.