Objective To examine whether acute dysglycaemia predicts death in people admitted to hospital with community acquired pneumonia. Design Multicentre prospective cohort study. Setting Hospitals and private practices in Germany, Switzerland, and Austria. Participants 6891 patients with community acquired pneumonia included in the German community acquired pneumonia competence network (CAPNETZ) study between 2003 and 2009. Main outcome measures Univariable and multivariable hazard ratios adjusted for sex, age, current smoking status, severity of community acquired pneumonia using the CRB-65 score (confusion, respiratory rate >30/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years), and various comorbidities for death at 28, 90, and 180 days according to serum glucose levels on admission. Results An increased serum glucose level at admission to hospital in participants with community acquired pneumonia and no pre-existing diabetes was a predictor of death at 28 and 90 days. Compared with participants with normal serum glucose levels on admission, those with mild acute hyperglycaemia (serum glucose concentration 6-10.99 mmol/L) had a significantly increased risk of death at 90 days (1.56, 95% confidence interval 1.22 to 2.01; P<0.001), and this risk increased to 2.37 (1.62 to 3.46; P<0.001) when serum glucose concentrations were ≥14 mmol/L. In sensitivity analyses the predictive value of serum glucose levels on admission for death was confirmed at 28 days and 90 days. Patients with pre-existing diabetes had a significantly increased overall mortality compared with those without diabetes (crude hazard ratio 2.47, 95% confidence interval 2.05 to 2.98; P<0.001). This outcome was not significantly affected by serum glucose levels on admission (P=0.18 for interaction). Conclusions Serum glucose levels on admission to hospital can predict death in patients with community acquired pneumonia without pre-existing diabetes. Acute hyperglycaemia may therefore identify patients in need of intensified care to reduce the risk of death from community acquired pneumonia.

BACKGROUND: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2–specific immunity correlate with disease severity. METHODS: In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS: Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4 ⁺ T cells dominated over CD8 ⁺ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 ⁺ and CD8 ⁺ T cells in general. CONCLUSION: Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING: The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.

Background: Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods: Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results: The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions: ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

Rationale: Patients with interstitial lung disease and acute respiratory failure have a poor prognosis especially if mechanical ventilation is required. Objectives: To investigate the outcome of patients with acute respiratory failure in interstitial lung disease undergoing extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or transplantation. Methods: This was a retrospective analysis of all patients with interstitial lung disease and acute respiratory failure treated with or without ECMO from March 2012 to August 2015. Measurements and Main Results: Forty patients with interstitial lung disease referred to our intensive care unit for acute respiratory failure were included in the analysis. Twenty-one were treated with ECMO. Eight patients were transferred by air from other hospitals within a range of 320 km (linear distance) for extended intensive care including the option of lung transplant. In total, 13 patients were evaluated, and eight were finally found to be suitable for lung transplantation from an ECMO bridge. Four patients from external hospitals were de novo listed during acute respiratory failure. Six patients underwent lung transplant, and two died on the waiting list after 9 and 63 days on ECMO, respectively. A total of 14 of 15 patients who did not undergo lung transplantation (93.3%) died after 40.3 ± 27.8 days on ECMO. Five out of six patients (83.3%) receiving a lung transplant could be discharged from hospital. Conclusions: ECMO is a lifesaving option for patients with interstitial lung disease and acute respiratory failure provided they are candidates for lung transplantation. ECMO is not able to reverse the poor prognosis in patients that do not qualify for lung transplantation.

BACKGROUND. COVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment. METHODS. Patients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. Results. The primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group. Conclusion. CCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies. Trial registration. ClinicalTrials.gov NCT04433910. Funding. Bundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.

Background: Changes in pulmonary hemodynamics and ventilation/perfusion were proposed as hallmarks of Coronavirus disease 2019 (COVID‐19)–induced acute respiratory distress syndrome (ARDS). Inhaled nitric oxide (iNO) may overcome these issues and improve arterial oxygenation.Methods: We retrospectively analyzed arterial oxygenation and pulmonary vasoreactivity in seven COVID‐19 ARDS patients receiving 20 ppm iNO for 15‐30 minutes.Results: The inhalation of NO significantly improved oxygenation. All patients with severe ARDS had higher partial pressures of oxygen and reduced pulmonary vascular resistance. Significant changes in pulmonary shunting were not observed.Conclusion: Overall, iNO could provide immediate help and delay respiratory deterioration in COVID‐19–induced moderate to severe ARDS.