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Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.

The primary objective of this study was to compare the plasma levels of copper, selenium, and zinc between critically ill COVID-19 patients and less severe COVID-19 patients. The secondary objective was to investigate the association of these trace element levels with adverse outcomes, including the duration of mechanical ventilation, occurrence of septic shock, and mortality in critically ill COVID-19 patients. All COVID-19 patients admitted to the ICU of the Geneva University Hospitals between 9 March 2020 and 19 May 2020 were included in the study. Plasma levels of copper, selenium and zinc were measured on admission to the ICU and compared with levels measured in COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. To analyze the association of trace elements with clinical outcomes, multivariate linear and logistic regressions were performed. Patients in the ICU had significantly lower levels of selenium and zinc and higher levels of copper compared to COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. In ICU patients, lower zinc levels tended to be associated with more septic shock and increased mortality compared to those with higher zinc levels (p = 0.07 for both). Having lower copper or selenium levels was associated with a longer time under mechanical ventilation (p = 0.01 and 0.04, respectively). These associations remained significant in multivariate analyses (p = 0.03 for copper and p = 0.04 for selenium). These data support the need for interventional studies to assess the potential benefit of zinc, copper and selenium supplementation in severe COVID-19 patients.

Background Influenza‐associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR‐confirmed influenza infection and treatment on intensive‐care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in‐hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. Results One hundred fifty‐eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non‐IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1–67.2]) and days of mechanical ventilation (OR 1.1 [1.1–1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non‐IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU‐mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3–253.4]), influenza A (OR 3.3 [1.4–7.8]), and higher SAPS II score (OR 1.07 [1.05–1.10]) were independent predictors of poor outcome. Interpretation High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Purpose In recent years, point-of-care ultrasonography (POCUS) has been integrated into internal medicine practice with most curricula composed of a single course. Despite competency acquisition during the course, a significant decline in proficiency occurs in the subsequent weeks due to a lack of regular practice and training. This study aims to evaluate the impact of a structured POCUS tutoring, on POCUS use and skills retention at 6 months. Methods In this randomized controlled trial, internal medicine residents were enrolled after completing a practical course focused on heart and lung ultrasonography. Residents assigned to the intervention group were paired with a tutor, and time slots were scheduled for bedside direct supervision over the following 6 months. The primary outcome was the proportion of residents who successfully completed at least 25 POCUS examinations six months after inclusion. Secondary outcomes included self- and blinded-expert-assessed POCUS competency skills. Results Between January and May 2022, 23 residents were included in the study. The intervention significantly increased the proportion of participants reaching the primary outcome (70% versus 0%; p  < 0.001) with a median of 27 (interquartile range, IQR, 6 to 44) supervised examinations performed versus 0 (IQR 0 to 0) in intervention and control arm respectively; p  < 0.001. After 6 months, proficiency was higher for most heart imaging but not for lung imaging, as assessed through self-assessment by participants or independently by blinded experts. Conclusion Structured POCUS supervision significantly enhances the number of POCUS examinations and proficiency at 6-months, particularly in applications requiring greater visuospatial skills.

Background Critical illness is known to reduce gut microbiota (GM) diversity, a change associated with adverse outcomes. Among potential mechanisms, splanchnic hypoperfusion may play a key role. Cardiac arrest (CA), characterized by transient global hypoperfusion, provides a relevant model to explore this effect. Results We conducted a secondary, propensity score-matched analysis of a cohort study investigating GM changes during early intensive care unit stay. Stool samples were collected at ICU admission (S1) and at least 24 h later (S2). GM profiling was performed using 16S rRNA sequencing. Shannon diversity index and taxonomic composition were compared between CA and non-CA patients. Propensity score matching and generalized linear models (GLM) were used to adjust for confounding. A total of 26 patients were included in this analysis (13 CA, 13 matched controls). At S1, CA patients had significantly lower GM diversity (Shannon index: 3.6 [3.0–3.8] vs. 4.3 [3.9–4.8], p  = 0.019). This was confirmed in the GLM ( β  = − 0.30, SE 0.12, p  = 0.022). At S2, diversity remained lower (3.2 [2.7–3.8] vs. 4.0 [3.7–4.3], p  = 0.064). While no global compositional shifts were observed between groups, differences in the abundance of specific taxa were noted. Conclusion CA is associated with reduced GM diversity in the first few days of intensive care unit admission compared to non-CA patients, supporting a role for splanchnic hypoperfusion in GM modulation. Further research should investigate clinical consequences and evaluate microbiota-targeted interventions in this high-risk population.

COVID-19 patients often present with rapidly progressing acute hypoxemic respiratory failure, requiring orotracheal intubation with different prognostic issues. However, ICU specialists lack predictive tools to stratify these patients. We conducted a single-center cross-sectional retrospective study to evaluate if the ROX index, measured under non-invasive oxygenation support, can predict ICU mortality in a COVID-19 intubated patient cohort. This study took place in the division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). We included all consecutive adult patients treated by non-invasive oxygenation support and requiring intubation for acute respiratory failure due to COVID-19 between 9 September 2020 and 30 March 2021, corresponding to the second local surge of COVID-19 cases. Baseline demographic data, comorbidities, median ROX between H0 and H8, and clinical outcomes were collected. Overall, 82 patients were intubated after failing a non-invasive oxygenation procedure. Women represented 25.6% of the whole cohort. Median age and median BMI were 70 (60–75) years and 28 (25–33), respectively. Before intubation, the median ROX between H0 and H8 was 6.3 (5.0–8.2). In a multivariate analysis, the median ROX H0–H8 was associated with ICU mortality as a protective factor with an odds ratio (95% CI) = 0.77 (0.60–0.99); p < 0.05. In intubated COVID-19 patients treated initially by non-invasive oxygenation support for acute respiratory failure, the median ROX H0–H8 could be an interesting predictive factor associated with ICU mortality.

COVID-19, a systemic multi-organ disease resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to result in a wide array of disease outcomes, ranging from asymptomatic to fatal. Despite persistent progress, there is a continued need for more accurate determinants of disease outcomes, including post-acute symptoms after COVID-19. In this study, we characterised the serum metabolomic changes due to hospitalisation and COVID-19 disease progression by mapping the serum metabolomic trajectories of 71 newly hospitalised moderate and severe patients in their first week after hospitalisation. These 71 patients were spread out over three hospitals in Switzerland, enabling us to meta-analyse the metabolomic trajectories and filter consistently changing metabolites. Additionally, we investigated differential metabolite–metabolite trajectories between fatal, severe, and moderate disease outcomes to find prognostic markers of disease severity. We found drastic changes in serum metabolite concentrations for 448 out of the 901 metabolites. These results included markers of hospitalisation, such as environmental exposures, dietary changes, and altered drug administration, but also possible markers of physiological functioning, including carboxyethyl-GABA and fibrinopeptides, which might be prognostic for worsening lung injury. Possible markers of disease progression included altered urea cycle metabolites and metabolites of the tricarboxylic acid (TCA) cycle, indicating a SARS-CoV-2-induced reprogramming of the host metabolism. Glycerophosphorylcholine was identified as a potential marker of disease severity. Taken together, this study describes the metabolome-wide changes due to hospitalisation and COVID-19 disease progression. Moreover, we propose a wide range of novel potential biomarkers for monitoring COVID-19 disease course, both dependent and independent of the severity.

Background During the pandemic of COVID‐19, the scientific community tried to identify the risk factors that aggravate the viral infection. Oral health and specifically periodontitis have been shown to have a significant impact on overall health. Current, yet limited, evidence suggests a link between periodontal status and severity of COVID‐19 infection. Objectives The present pilot study aimed to assess whether younger patients (≤60 years) that have been hospitalized in the intensive care unit (ICU) for severe COVID‐19 infection were susceptible to severe periodontitis. Material and Methods All dentate patients ≤60 years of age diagnosed with COVID‐19 and surviving hospitalization in the ICU were considered for inclusion. Susceptibility to periodontitis was determined by assessing radiographic bone loss (RBL) in recent dental radiographs (posterior bitewings, periapical, and panoramic X‐rays). RBL in % was obtained from the most affected tooth and patients were classified into: Stage I, RBL ≤ 15%; Stage II, RBL = 15%−33% and Stage III/IV, RBL ≥ 33%. The grade was defined using the RBL to age ratio on the most severely affected tooth. Patients were attributed to: Grade A, ratio <0.25; Grade B, ratio 0.25−1 and Grade C, ratio >1. Patients classified into Stage III/IV and Grade C were considered highly susceptible to periodontitis. Results Of 87 eligible patients, 30 patients were finally assessed radiographically and/or clinically; from the remaining 57 patients, 16 refused participation for various reasons and 41 could not be reached. Based on the radiographic assessment, all patients were periodontally compromised. Half of them were classified with Stage III/IV and Grade B or C; 26.7% were classified with Stage III/IV and Grade C. Conclusions The present pilot study showed that about half of the patients suffering from severe forms of COVID‐19 infection in need of ICU admission suffered also from severe periodontitis, and about one‐fourth of them were highly susceptible to it.

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.