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.

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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. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) 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 fecal 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, such as Enterococcus . In contrast, less severe clinical outcomes are 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.

Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) (P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% (P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed.