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Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04410263 .

Patient safety is a priority in healthcare, yet it is unclear how sources of errors should best be analyzed. Eye tracking is a tool used to monitor gaze patterns in medicine. The aim of this study was to analyze the distribution of visual attention among critical care nurses performing non-simulated, routine patient care on invasively ventilated patients in an ICU. ICU nurses were tracked bedside in daily practice. Eight specific areas of interest were pre-defined (respirator, drug preparation, medication, patient data management system, patient, monitor, communication and equipment/perfusors). Main independent variable and primary outcome was dwell time, secondary outcomes were hit ratio, revisits, fixation count and average fixation time on areas of interest in a targeted tracking-time of 60 min. 28 ICU nurses were analyzed and the average tracking time was 65.5 min. Dwell time was significantly higher for the respirator (12.7% of total dwell time), patient data management system (23.7% of total dwell time) and patient (33.4% of total dwell time) compared to the other areas of interest. A similar distribution was observed for fixation count (respirator 13.3%, patient data management system 25.8% and patient 31.3%). Average fixation time and revisits of the respirator were markedly elevated. Apart from the respirator, average fixation time was highest for the patient data management system, communication and equipment/perfusors. Eye tracking is helpful to analyze the distribution of visual attention of critical care nurses. It demonstrates that the respirator, the patient data management system and the patient form cornerstones in the treatment of critically ill patients. This offers insights into complex work patterns in critical care and the possibility of improving work flows, avoiding human error and maximizing patient safety.

Background Prehospital point-of-care ultrasound allows an unstable patient to be rapidly and accurately assessed. However, we are concerned that an excessive focus on the ultrasound device, in an already demanding emergency medical service environment, may distract from patient care, potentially leading to reduced situational awareness and the neglect of other crucial instruments, such as the patient monitor. Thus, in this study, we examined the influence of prehospital ultrasound on situational awareness, by studying the degree to which physicians were distracted from the patient monitor. Methods We observed HEMS physicians in a simulated setting and analysed their gaze behaviour using an eye tracker placed on three areas of interests: the ultrasound device, the patient and the patient monitor. In the course of the experiment, the simulated patient desaturated, which was presented on the patient monitor. The primary outcome was the fraction of gaze distribution across the three areas of interest, while secondary outcomes were different gaze metrics (dwell time, revisits, average duration of visual intake and entry time) on the patient monitor. We then compared the participants who noticed the patient’s deterioration with those who did not. Results In 75% of cases, the severely decreased oxygen saturation went unnoticed during the test. Moreover, the gaze distribution of the two groups differed, with the group that recognised the deterioration focusing longer on the patient monitor (7.8% (95% CI 5–10.7) vs 0.1% (95% CI 0–0.3), p : 0.124). Conclusions The task of performing an ultrasound examination appears to overwhelm some participants and distract them from other aspects of the scenario. Efforts to mitigate distractions and optimise the use of prehospital ultrasound, such as education, a focus on human factors aspects and standardisation, are crucial for maximising the potential benefits of prehospital ultrasound.

Background Necrotizing soft-tissue infections are infections with high mortality. The use of immunoglobulins within a combination therapy including broad-spectrum antibiotics has been debated. We assessed potential benefits of immunoglobulins and hypothesized that they were associated with a treatment benefit in a high-resource setting. Methods Patients with necrotizing soft-tissue infection hospitalized in the tertiary intensive care unit of the University Hospital of Zurich, Switzerland, between 2008 and 2020 were included retrospectively. The association between immunoglobulin administration and in-hospital survival, intensive care unit length of stay, the incidences of acute renal failure, acute respiratory distress syndrome and septic shock were analyzed. Results After adjustment for confounders, no difference for in-hospital survival (hazard ratio 2.20, 95% confidence interval [CI] 0.24–20.20, p = 0.5), intensive care unit length of stay (subhazard ratio [SHR] 0.90, CI 0.41–1.98, p = 0.8) and the development of acute respiratory distress syndrome (SHR 1.2, CI 0.36–4.03, p = 0.77) was observed in patients with or without immunoglobulin treatment. The Simplified Acute Physiology Score II, the risk of developing acute renal failure (SHR 2.86, CI 1.33–6.15, p = 0.01) and septic shock (SHR 1.86, CI 1.02–3.40, p = 0.04) was higher in patients treated with immunoglobulins, possibly reflecting a higher disease severity beyond measured confounders. Conclusions No clear evidence for a benefit of immunoglobulins in our cohort with consistent antibiotic use was found. Patients receiving immunoglobulins appeared more severely ill. Complementary to high treatment standards and appropriate antibiotics including beta lactams and protein synthesis inhibitors, immunoglobulins should be administered on a case-to-case basis, at least while more evidence from larger randomized controlled trials is missing.

BackgroundBacterial superinfections are common in patients with acute respiratory distress syndrome (ARDS) but diagnosing them is challenging. Exhaled carbon dioxide (V’CO2) may be increased during bacterial infection, suggesting a potential marker for detecting bacterial superinfections in ARDS patients.MethodsIn a prospective cohort study of mechanically ventilated adult patients with ARDS due to SARS-CoV-2 in a tertiary intensive care unit, we assessed V’CO2 measurements from continuous volumetric capnography and calculated daily median V’CO2 levels. The primary outcome was to determine if a first substantial increase in daily median V’CO2 was associated with a first bacterial superinfection. Protocolised microbiological sampling and adjudicated clinical interpretations were used to determine the onset of a first superinfection.ResultsA total of 150 days of continuous volumetric capnography were analysed in 31 mechanically ventilated adult patients with ARDS due to SARS-CoV-2. We observed 10 patients (32%) with a first episode of substantial increase of daily median V’CO2, and 12 (39%) patients with a first bacterial superinfection. A V’CO2 increase was not associated with a superinfection on the same day (OR 3.47, 95% CI 0.64 to 18.92, p=0.15, adjusted for age and gender). Investigating all 150 test days of median V'CO2 revealed a poor sensitivity (17%, 95% CI 2% to 48%) for detecting superinfections. However, a first V'CO2 increase indicated superinfection with high specificity (94%, 95% CI 89% to 98%). Patients with superinfections showed higher daily median V'CO2 levels (210 mL/min) than those without (176 mL/min, p<0.001), even after adjusting for age and gender (OR 1.56, 95% CI 1.16 to 2.08, p=0.003).ConclusionsA sudden increase in daily median V’CO2 did not reliably detect bacterial superinfections, which was reflected in a poor sensitivity and inability to rule out superinfections in patients without V’CO2 increase. Nevertheless, high specificity suggests that V’CO2 may be useful to rule in superinfections in patients with ARDS.Trial registration numberNCT04410263.

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report.

Background In intensive care units (ICUs) treating patients with Coronavirus disease 2019 (COVID-19) invasive ventilation poses a high risk for aerosol and droplet formation. Surface contamination of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) or bacteria can result in nosocomial transmission. Methods Two tertiary care COVID-19 intensive care units treating 53 patients for 870 patient days were sampled after terminal cleaning and preparation for regular use to treat non-COVID-19 patients. Results A total of 176 swabs were sampled of defined locations covering both ICUs. No SARS-CoV-2 ribonucleic acid (RNA) was detected. Gram-negative bacterial contamination was mainly linked to sinks and siphons. Skin flora was isolated from most swabbed areas and Enterococcus faecium was detected on two keyboards. Conclusions After basic cleaning with standard disinfection measures no remaining SARS-CoV-2 RNA was detected. Bacterial contamination was low and mainly localised in sinks and siphons.

Objectives Critically ill coronavirus disease 2019 (COVID‐19) patients are characterised by a severely dysregulated cytokine profile and elevated neutrophil counts, impacting disease severity. However, it remains unclear how neutrophils contribute to pathophysiology during COVID‐19. Here, we assessed the impact of the dysregulated cytokine profile on the regulated cell death (RCD) programme of neutrophils. Methods Regulated cell death phenotype of neutrophils isolated from critically ill COVID‐19 patients or healthy donors and stimulated with COVID‐19 or healthy plasma ex vivo was assessed by flow cytometry, time‐lapse microscopy and cytokine multiplex analysis. Immunohistochemistry of COVID‐19 patients and control biopsies were performed to assess the in situ neutrophil RCD phenotype. Plasma cytokine levels of COVID‐19 patients and healthy donors were measured by multiplex analysis. Clinical parameters were correlated to cytokine levels of COVID‐19 patients. Results COVID‐19 plasma induced a necroptosis‐sensitive neutrophil phenotype, characterised by cell lysis, elevated release of damage‐associated molecular patterns (DAMPs), increased receptor‐interacting serine/threonine‐protein kinase (RIPK) 1 levels and mixed lineage kinase domain‐like pseudokinase (MLKL) involvement. The occurrence of neutrophil necroptosis MLKL axis was further confirmed in COVID‐19 thrombus and lung biopsies. Necroptosis was induced by the tumor necrosis factor receptor 1 (TNFRI)/TNF‐α axis. Moreover, reduction of soluble Fas ligand (sFasL) levels in COVID‐19 patients and hence decreased signalling to Fas directly increased RIPK1 levels, exacerbated TNF‐driven necroptosis and correlated with disease severity, which was abolished in patients treated with glucocorticoids. Conclusion Our results suggest a novel role for sFasL signalling in the TNF‐α‐induced RCD programme in neutrophils during COVID‐19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome. This work highlights the role of cell death ambiguity in neutrophils and its contribution to pathophysiology during critical COVID‐19. The inflammatory COVID‐19 environment provoked a TNF‐α‐induced necroptosis‐sensitive neutrophil subpopulation, characterised by elevated release of DAMPs, increased RIPK1 levels and a pivotal role for MLKL. Neutrophil necroptosis through the RIPK1‐RIPK3‐MLKL axis was further confirmed in COVID‐19 thrombus and lung biopsies. Blunted Fas engagement by sFasL was identified to drive elevated RIPK1 levels upon TNF‐α‐induced necroptosis, while decreased sFasL plasma levels in critically ill COVID‐19 patients correlated to elevated disease severity, which was masked by glucocorticoid treatment.

Introduction: Closed-loop ventilation modes are increasingly being used in intensive care units to ensure more automaticity. Little is known about the visual behavior of health professionals using these ventilation modes. The aim of this study was to analyze gaze patterns of intensive care nurses while ventilating a patient in the closed-loop mode with Intellivent adaptive support ventilation® (I-ASV) and to compare inexperienced with experienced nurses. Materials and Methods: Intensive care nurses underwent eye-tracking during daily care of a patient ventilated in the closed-loop ventilation mode. Five specific areas of interest were predefined (ventilator settings, ventilation curves, numeric values, oxygenation Intellivent, ventilation Intellivent). The main independent variable and primary outcome was dwell time. Secondary outcomes were revisits, average fixation time, first fixation and fixation count on areas of interest in a targeted tracking-time of 60 min. Gaze patterns were compared between I-ASV inexperienced ( n = 12) and experienced ( n = 16) nurses. Results: In total, 28 participants were included. Overall, dwell time was longer for ventilator settings and numeric values compared to the other areas of interest. Similar results could be obtained for the secondary outcomes. Visual fixation of oxygenation Intellivent and ventilation Intellivent was low. However, dwell time, average fixation time and first fixation on oxygenation Intellivent were longer in experienced compared to inexperienced intensive care nurses. Discussion: Gaze patterns of intensive care nurses were mainly focused on numeric values and settings. Areas of interest related to traditional mechanical ventilation retain high significance for intensive care nurses, despite use of closed-loop mode. More visual attention to oxygenation Intellivent and ventilation Intellivent in experienced nurses implies more routine and familiarity with closed-loop modes in this group. The findings imply the need for constant training and education with new tools in critical care, especially for inexperienced professionals.