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The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.

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., Journal of Clinical Monitoring and Computing, 35 (6), ISSN:1573-2614, ISSN:1387-1307

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.

Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with pre-disposition to severe COVID-19. Here, we screened for such autoantibodies in 103 critically-ill COVID-19 patients in a tertiary intensive care unit 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 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 (herpes simplex viruses types 1 and 2, HSV-1/-2; and/or cytomegalovirus, CMV) reactivations, which are linked to worse clinical outcomes. Indeed, all seven tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesvirus reactivations, and analysis revealed that these patients were substantially more likely to experience CMV reactivation than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for systemic steroid treatment (odds ratio 7.28, 95%-CI 1.14-46.31, p=0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates herpesvirus reactivations in critically-ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.

Patient safety has become a high priority in health care. The recognition, prevention and reduction of human errors are crucial for patient care. Diverse approaches to analyze roots of errors exist, however they all bear relevant limitations. In contrast, the technology of eye-tracking offers objective and measurable parameters linked to eye movements, allowing temporal and spatial assessment of visual patterns. Diverse studies in critical care have proved the usefulness of eye-tracking to analyze real-life scenarios. These insights could contribute to increased patient safety.

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients., Author summary COVID-19 caused by SARS-CoV-2 induces immune-paralysis characterized by misdirected host responses and altered levels of inflammatory mediators. Additionally, bacterial superinfections can further exacerbate the disease. Here, we report an in-depth functional characterization of the effector response and phenotypic properties of neutrophils and monocytes derived from critically ill COVID-19 patients towards bacterial superinfection. We show that elevated levels of specific cytokine clusters, positively correlate with the development of bacterial superinfections in these patients. Neutrophils and monocytes of critically ill COVID-19 patients showed impaired bactericidal capacity, which was mediated by elevated inflammatory mediators in the plasma. The observed impaired bactericidal capacity in critically ill COVID-19 patients was due to reduced classical effector functions of neutrophils and monocytes. Interestingly, lower levels of overall inflammatory mediators as well as reduction in length of ICU stay and ventilation-days in critically ill COVID-19 patients treated with dexamethasone was observed. These data suggest that the exhaustion and paralysis of the cellular innate immunity against bacterial challenge in critically ill COVID-19 patients is driven by a misdirected host-response, characterized by a hyperinflammatory environment including dysregulated cytokine levels. These results further emphasize the utility and importance of dampening these inflammatory mediators via broad anti-inflammatory therapy in COVID-19 patients, which improves the antibacterial effector functions of neutrophils and monocytes.

Background Patients in intensive care units are prone to the occurrence of medication errors. Look-alike, sound-alike drugs with similar drug names can lead to medication errors and therefore endanger patient safety. Capitalisation of distinct text parts in drug names might facilitate differentiation of medication labels. The aim of this study was to test whether the use of such ‘tall man’ lettering (TML) reduces the error rate and to examine effects on the visual attention of critical care nurses while identifying syringe labels. Methods This was a prospective, randomised in situ simulation conducted at the University Hospital Zurich, Zurich, Switzerland. Under observation by eye tracking, 30 nurses were given 10 successive tasks involving the presentation of a drug name and its selection from a dedicated set of 10 labelled syringes that included look-alike and sound-alike drug names, half of which had TML-coded labels. Error rate as well as dwell time, fixation count, fixation duration and revisits were analysed using a linear mixed-effects model analysis to compare TML-coded with non-TML-coded labels. Results TML coding of syringe labels led to a significant decrease in the error rate (from 5.3% (8 of 150 in non-TML-coded sets) to 0.7% (1 of 150 in TML-coded sets), p, BMJ Quality & Safety, 32 (1), ISSN:2044-5423, ISSN:2044-5415

BackgroundEvidence to date indicates that mortality of acute coronavirus disease (COVID-19) is higher in men than in women. Conversely, women seem more likely to suffer from long-term consequences of the disease and pronounced negative social and economic impacts. Sex- and gender specific risk factors of COVID-19-related long-term effects are unknown. MethodsWe conducted a multicentre prospective observational cohort study of 5838 (44.6% women) individuals in Switzerland who were tested positive for SARS-CoV-2 RNA between February and December 2020. Of all surviving individuals who met the inclusion criteria, 2799 (1285 [45.9%] women) completed a follow-up questionnaire. FindingsAfter a mean follow-up time of 197{+/-}77 days, women more often reported at least one persistent symptom (43.0% vs 31.5%, p

Background: Lung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes. Method: Prospective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume 2O, peak pressure 2O, peripheral oxygen saturation ≥88% and dynamic mechanical power Results: Forty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001). Conclusion: Among critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.

Critically ill COVID-19 patients are characterized by a severely dysregulated cytokine profile and elevated neutrophil counts, which are thought to contribute to disease severity. However, to date it remains unclear how neutrophils contribute to pathophysiology during COVID-19. Here, we assessed the impact of the dysregulated cytokine profile on the tightly regulated cell death program of neutrophils. We show that in a subpopulation of neutrophils, canonical apoptosis was skewed towards rapidly occurring necroptosis. This phenotype was characterized by abrogated caspase-8 activity and increased RIPK1 levels, favoring execution of necroptosis via the RIPK1-RIPK3-MLKL axis, as further confirmed in COVID-19 biopsies. Moreover, reduction of sFas-L levels in COVID-19 patients and hence decreased signaling to Fas directly increased RIPK1 levels and correlated with disease severity. Our results suggest an important role for Fas signaling in the regulation of cell death program ambiguity via the ripoptosome in neutrophils during COVID-19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome.

The impact of secondary bacterial infections (superinfections) in COVID-19 is not well understood. In this prospective, monocentric cohort study we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days (VFDs) at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37, 95%-CI 0.15-0.90, p=0.028). Patients with pulmonary superinfections have a higher incidence of bacteraemia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy., Graphical Abstract, Buehler et al. show that detection of bacterial pulmonary superinfection is associated with a more severe disease course in COVID-19 patients, especially a lower likelihood of being alive and off invasive mechanical ventilation at study day 28 (ventilator-free days at 28 days).

Supplemental Digital Content is available in the text., OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm–2), functional capillary density (mm × mm–2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (μm × s–1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s–1) and capillary RBC microaggregates (4 s–1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.

Bromelain-based enzymatic debridement has emerged as an alternative to surgical eschar removal. Indications include partial thickness, mixed pattern, and full-thickness burns. Enzymatic debridement has been approved by the European Medicines Agency for treating burn wounds affecting15% total body surface area (TBSA). Data and evidence for the treatment of areas15% TBSA in one session is scarce. The aim of this retrospective study was to retrospectively analyze off-label use of enzymatic debridement in a single burn center for large TBSA burns.Between 01/2017 and 12/2018, 59 patients with partial- to full-thickness burns underwent enzymatic debridement in a single center study. Patients were categorized into two groups: the regular use group with a treated area less than 15% TBSA and the off-label group (OG) with larger TBSA debrided in one session. Treatment was evaluated for systemic inflammatory reaction, bleeding, hemodynamic instability and electrolyte shifts.In total, 49 patients were treated in the regular use group with a median application area of 6% (IQR 2.5-9.5) and 10 patients were treated in the off-label group with a median application area of 18% (IQR 15-19) TBSA. We found no significant differences regarding blood pressure, body temperature or hemodynamic stability during and after enzymatic debridement. No treatment-related serious adverse events were observed in either group. Catecholamine use was similar in both groups. No differences in leukocyte counts, CRP, PCT and lactate prior to application and during the following three days were observed. Sodium, potassium, chloride and phosphate levels did not differ. We found no evidence of an electrolyte shift. Survival was 49 of 49 patients (100%) in the RG and 7 of 10 patients (70%) in the OG (p = 0.004).Enzymatic debridement did not result in any expected or unexpected side effects in the patient groups investigated. These preliminary results indicate the potential safety of bromelain-based enzymatic debridementin the treatment of burns greater than 15% TBSA.

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., Frontiers in Medicine, 8, ISSN:2296-858X

Background Patient safety is a top priority in healthcare. Little is known about the visual behaviour of professionals during high-risk procedures. The aim of this study was to assess feasibility, usability and safety of eye-tracking to analyse gaze patterns during the extubation-process in the intensive care unit. Methods Eye-tracking was used in this observational study to analyse the extubationprocess in 22 participants. Independent variables were average fixation time, dwell time, fixation count, hit ratio and revisit count for eighteen areas of interest. Primary outcome was dwell time for all areas of interest. Secondary outcomes were average fixation time, fixation count and revisits. In subgroup analyses, experienced and non-experienced physicians were compared. Results The most important area of interest was the patient, as analyzed by dwell time. Fixation of other areas of interest varied significantly among participants. Only 54% checked ventilator respiratory rate, despite declaring it as important in questionnaires. Other neglected areas of interest included tidal volume (59%), peak pressure (63.6%), CO2 (63.6%), temperature (18.2%), blood pressure (59%) and heart rate (68%). Experienced physicians gazed more frequently and longer at the patient while spending less time on monitor and ventilator parameters. Conclusions Eye-tracking can demonstrate that there is a mismatch between physicians' subjective evaluations and corresponding objective real-life measurements. Structured and standardized extubation-processes should be performed to improve patient safety. In the immediate post-extubation phase, long dwell time on the patient shows that clinical observation remains the most important cornerstone beyond monitoring devices.

Background: While superinfections are associated with unfavourable disease course, their impact on clinical outcomes in critically ill COVID-19 patients remains largely unknown. We aimed to investigate the impact of superinfections in critically ill patients with COVID-19. Methods: In this prospective single centre cohort study in an intensive care unit (ICU) setting patients aged ≥ 18 years with COVID-19 Acute Respiratory Distress Syndrome (CARDS) and confirmed SARS-CoV-2 infection were assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions (TBS), bronchoalveolar lavages (BAL) and blood. Our primary outcome was ventilator-free survival on day 28 in patients with and without clinically relevant superinfection. Further outcomes included the association of superinfection with ICU length of stay, incidence of bacteremia, viral reactivations, and fungal colonization. Findings: In a total of 45 critically ill COVID-19 patients, we identified 19 patients with superinfections (42·2%) by longitudinal analysis of 433 TBS, 35 BAL and 455 blood samples, respectively. On average, superinfections were detected on day 10 after ICU admission despite the majority of patients already being on empiric antibiotic therapy. The most frequently isolated clinically relevant bacteria were Enterobacter/Citrobacter , Klebsiella spp., Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. Ventilator-free survival (VFS) at 28 days was substantially lower in patients with superinfection (subhazard ratio 0·37, 95%-CI 0·15-0·90, p=0·028). Patients with pulmonary superinfections more often had bacteraemia, virus reactivations, yeast colonization, and needed ICU treatment for a significantly longer time. Interpretation: The detection of superinfections was frequent and associated with reduced ventilator-free survival. A more severe disease course in critically ill COVID-19 patients with superinfections thus seems likely, also reflected by a substantially increased ICU length of stay despite empirical broad-spectrum antimicrobial therapy. Longitudinal microbiologic sampling in COVID-19 patients could allow targeted antimicrobial therapy, and therefore minimize the use of broad-spectrum and reserve antibiotics. Funding: Promedica-Foundation, unrestricted grant. Declaration of Interests: All other authors have no conflict of interest. Ethics Approval Statement: The study was approved by the local ethics committee of the Canton of Zurich, Switzerland (Kantonale Ethikkommission Zurich BASEC ID 2020 - 00646).