A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2.

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.

A Dedicated Expert ECMO-Team and Strict Patient Selection Improve Survival of Patients with Severe SARS-CoV-2 ARDS Supported by VV-ECMO.

The SARS-CoV-2 pandemic has overwhelmed health care systems worldwide since its first wave. Intensive care units have been under a significant amount of pressure as patients with the most severe form of the disease presented with acute respiratory distress syndrome (ARDS). A proportion of them experienced refractory acute respiratory failure and had to be supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO). The present retrospective study reports the experiences of our ECMO center in the management of COVID-19 patients with refractory ARDS. Patient characteristics and outcomes are presented through the different waves of the pandemic. A cohort study was conducted on patients with refractory ARDS due to COVID-19 infection who were admitted to the intensive care unit (ICU) at the Geneva University Hospital and supported with VV-ECMO between 14 March 2020 and January 2022. The VV-ECMO implementation criteria were defined according to an institutional algorithm validated by the local crisis unit of the hospital and the Swiss Society of Intensive Care Medicine. Among the 500 ARDS patients admitted to our ICU, 41 patients with a median age of 57 (52−63) years, a body mass index (BMI) of 28 (26−32) kg/m2, and a SAPS II score of 57 (47−67), and 27 (66%) of whom were men required VV-ECMO. None of the patients were vaccinated. The time of ventilation, including noninvasive ventilation (NIV) and mechanical ventilation (MV), and the time of MV before ECMO were 7 (4−11) days and 4 (1−7) days, respectively. The time under ECMO was 20 (10−27) days. The ICU and hospital lengths of stay were 36 (21−45) days and 45 (33−69) days, respectively. The survival rate for patients on ECMO was 59%. Comparative analysis between survivors and non-survivors highlighted that survivors had a significantly shorter ventilation duration before ECMO (NIV + MV: 5.5 (1.3−9) vs. 9 (6.5−13.5) days, p = 0.0026 and MV alone: 1.6 (0.4−5.5) vs. 5.8 (5−8) days, p < 0.0001). The management of patients on ECMO by an experienced ECMO team dedicated to this activity was associated with improved survival (78% vs. 28%, p = 0.0012). Between the first wave and the following waves, patients presented with a higher incidence of ventilator-associated pneumonia (100% vs. 82%, p = 0.0325) but had better survival rates (74% vs. 35%, p = 0.024). The present study suggests that both the prompt insertion of VV-ECMO to control refractory hypoxemia and the involvement of an ECMO team improve the survival of COVID-19 patients.

Is the prognosis of non-hypertensive, COVID-19 patients treated with renin-angiotensin-aldosterone system inhibitors more uncertain?

Previous studies suggested that ongoing treatment with renin-angiotensin-aldosterone system (RAAS) inhibitor drugs may alter the course of SARS-CoV-2 infection and promote the development of more severe forms of the disease. The authors conducted a comparative, observational study to retrospectively analyze data collected from 394 patients admitted to ICU due to SARS-CoV-2 pneumonia. The primary aim of the study was to establish an association between the use of RAAS inhibitor drugs and mortality in the ICU. The secondary aims of the study were to establish an association between the use of RAAS inhibitor drugs and clinical severity at ICU admission, the need for tracheal intubation, total days of mechanical ventilation, and the ICU length of stay. The authors found no statistically significant difference in ICU mortality between patients on RAAS inhibitor drugs at admission and those who were not (31.3% versus 26.2% mortality, p-value 0.3). However, the group of patients taking RAAS inhibitor drugs appeared to be more critical at ICU admission, and this difference became statistically significant in the subgroup of non-hypertensive patients. ICU mortality in the subgroup of non-hypertensive patients treated with RAAS inhibitor drugs also tended to be higher. Overexpression of the angiotensin-converting enzyme 2 (ACE2) in human cells, induced by RAAS inhibitor drugs, promotes viral entry-replication of SARS-CoV-2 and alters the basal balance of the RAAS, which may explain the findings observed in the present study. These phenomena may be amplified in non-hypertensive patients treated with RAAS inhibitor therapy.

How things changed during the COVID-19 pandemic's first year: A longitudinal, mixed-methods study of organisational resilience processes among healthcare workers.

COVID-19 had a huge impact on healthcare systems globally. Institutions, care teams and individuals made considerable efforts to adapt their practices. The present longitudinal, mixed-methods study examined a large sample of healthcare institution employees in Switzerland. Organisational resilience processes were assessed by identifying problematic real-world situations and evaluating how they were managed during three phases of the pandemic's first year. Results highlighted differences between resilience processes across the different types of problematic situations encountered by healthcare workers. Four configurations of organisational resilience were identified depending on teams' performance and ability to adapt over time: "learning from mistakes", "effective development", "new standards" and "hindered resilience". Resilience trajectories differed depending on professional categories, hierarchical status and the problematic situation's perceived severity. Factors promoting or impairing organisational resilience are discussed. Findings highlighted the importance of individuals', teams' and institutions' meso- and micro-level adaptations and macro-level actors' structural actions.

How Can We Help Healthcare Workers during a Catastrophic Event Such as the COVID-19 Pandemic?

Healthcare workers (HCWs) have significantly suffered during the COVID-19 pandemic, reporting a high prevalence of anxiety, depression and post-traumatic stress disorder (PTSD). We investigated with this survey whether HCWs benefitted from supportive measures put in place by hospitals and how these measures were perceived. This cross-sectional survey, which was conducted during the first wave of COVID-19 at the Geneva University Hospitals, Switzerland, between May and July 2021, collected information on the use and perception of practical and mental health support measures provided by the hospital. In total, 3461 HCWs participated in the study. Regarding the practical support measures, 2896 (84%) participants found them useful, and 2650 (76%) used them. Regarding the mental health support measures, 3149 (90%) participants found useful to have the possibility of attending hypnosis sessions, 3163 (91%) to have a psychologist within hospital units, 3202 (93%) to have a medical nursing psychiatric permanence available seven days a week, and 3171 (92%) to have a hotline available seven days a week. In total, 436 (13%) HCWs used at least one of the available mental health support measures. During the COVID-19 pandemic, the support measures were valued by HCWs. Given the high prevalence of psychiatric issues among HCWs, these measures seem necessary and are likely to have alleviated the suffering of HCWs.

Delayed intubation is associated with mortality in patients with severe COVID-19: A single-centre observational study in Switzerland.

INTRODUCTION: Switzerland experienced two waves of COVID-19 in 2020, but with a different ICU admission and treatment management strategy. The timing of ICU admission and intubation remains a matter of debate in severe patients. The aim of our study was to describe the characteristics of ICU patients between two subsequent waves of COVID-19 who underwent a different management strategy and to assess whether the timing of intubation was associated with differences in mortality. PATIENTS AND METHODS: We conducted a prospective observational study of all adult patients with acute respiratory failure due to COVID-19 who required intubation between the 9th of March 2020 and the 9th of January 2021 in the intensive care unit (ICU) at Geneva University Hospitals, Switzerland. RESULTS: Two hundred twenty-three patients were intubated during the study period; 124 during the first wave, and 99 during the second wave. Patients admitted to the ICU during the second wave had a higher SAPS II severity score (52.5 vs. 60; p = 0.01). The time from hospital admission to intubation was significantly longer during the second compared to the first wave (4 days [IQR, 1-7] vs. 2 days [IQR, 0-4]; p < 0.01). All-cause ICU mortality was significantly higher during the second wave (42% vs. 23%; p < 0.01). In a multivariate analysis, the delay between hospital admission and intubation was significantly associated with ICU mortality (OR 3.25 [95% CI, 1.38-7.67]; p < 0.05). CONCLUSIONS: In this observational study, delayed intubation was associated with increased mortality in patients with severe COVID-19. Further randomised controlled trials are needed.

Hypophosphatemia on ICU Admission Is Associated with an Increased Length of Stay in the ICU and Time under Mechanical Ventilation.

Hypophosphatemia is frequently observed in the ICU and is associated with several impairments such as respiratory failure or infections. We hypothesized that hypophosphatemia on ICU admission is associated with a prolonged duration of mechanical ventilation and ICU length of stay (LOS), particularly in COVID-19 patients. This cross-sectional study analyzed data from 1226 patients hospitalized in the ICU of the Geneva University Hospitals from August 2020 to April 2021. Patients were categorized as having hypophosphatemia (phosphatemia ≤ 0.8 mmol/L) or non-hypophosphatemia (phosphatemia > 0.8 mmol/L) on ICU admission. Linear regressions were performed to investigate the association between hypophosphatemia on ICU admission and ICU LOS and duration of mechanical ventilation. Overall, 250 (20%) patients presented hypophosphatemia on ICU admission. In the univariable analysis, hypophosphatemic patients had longer ICU LOS than non-hypophosphatemic patients, 7.4 days (±10.4) versus 5.6 days (±8.3), (p < 0.01). Hypophosphatemia on ICU admission was associated with a prolonged duration of mechanical ventilation, 7.4 days (±11.2) versus 5.6 days (±8.9), (p < 0.01). These associations were confirmed in the multivariable analysis (p < 0.01). In the subgroup of COVID-19 patients, a significant association between hypophosphatemia and ICU LOS and duration of mechanical ventilation was also observed. In conclusion, hypophosphatemia on ICU admission is associated with a longer ICU LOS and time under mechanical ventilation, both in the general ICU population and in COVID-19 patients.

Mental health outcomes of ICU and non-ICU healthcare workers during the COVID-19 outbreak: a cross-sectional study.

BACKGROUND: Intensive care workers are known for their stressful work environment and for a high prevalence of mental health outcomes. The aim of this study was to evaluate the mental health, well-being and changes in lifestyle among intensive care unit (ICU) healthcare workers (HCW) during the first wave of the COVID-19 pandemic and to compare these results with those of HCW in other hospital units. Another objective was to understand which associated factors aggravate their mental health during the COVID-19 outbreak. METHODS: This cross-sectional survey collected socio-demographic data, lifestyle changes and mental health evaluations as assessed by the Generalized Anxiety Disorder 7 items (GAD-7), the Patient Health Questionnaire 9 items (PHQ-9), the Peritraumatic Distress Inventory (PDI) and the World Health Organization Well-Being Index (WHO-5) from the 28th May to 7th July 2020. The study was carried out at Geneva University Hospitals, a group of eight public hospitals in Switzerland. ICU HCW were analyzed for mental health outcomes and lifestyles changes and then compared to non-ICU HCW. A series of linear regression analyses were performed to assess factors associated with mental health scores. RESULTS: A total of 3461 HCW were included in the study, with 352 ICU HCW. Among ICU HCW, 145 (41%) showed low well-being, 162 (46%) symptoms of anxiety, 163 (46%) symptoms of depression and 76 (22%) had peritraumatic distress. The mean scores of GAD-7, PHQ-9 and WHO-5 were worse in ICU HCW than in non-ICU HCW (p < 0.01). Working in the ICU rather than in other departments resulted in a change of eating habits, sleeping patterns and alcohol consumption (p < 0.01). Being a woman, the fear of catching and transmitting COVID-19, anxiety of working with COVID-19 patients, work overload, eating and sleeping disorders as well as increased alcohol consumption were associated with worse mental health outcomes. CONCLUSION: This study confirms the suspicion of a high prevalence of anxiety, depression, peritraumatic distress and low well-being during the first COVID-19 wave among HCW, especially among ICU HCW. This allows for the identification of associated risk factors. Long-term psychological follow-up should be considered for HCW.

Impact of nutritional therapy during the first wave of the COVID-19 pandemic in intensive care patients: A retrospective observational study.

BACKGROUND & AIMS: The COVID-19 pandemic has caused major organizational challenges to healthcare systems concerning staff, material and bed availability. Nutrition was not a priority in the intensive care unit (ICU) at the beginning of the pandemic with the need for simplified protocols. We aimed to assess the impact of a simplified nutritional protocol for critically ill COVID-19 patients during the pandemic first wave. METHODS: We included all patients with SARS-CoV-2 infections, admitted to the ICU of the Geneva University Hospitals for at least 4 days from March 9 to May 19, 2020. Data on the route and solution of nutritional therapy, prescribed and received volume, calorie and protein intake, amount of insulin, propofol and glucose administered were collected daily during the entire ICU stay. We compared nutritional outcomes between patients admitted to the ICU before and after implementing the simplified nutritional protocol using unpaired t-test. RESULTS: Out of 119 patients, 48 were hospitalized in the ICU before, 47 across and 24 after the implementation of the nutritional protocol. The mean age was 63.2 (±12.7) years and 76% were men without significant difference between before and after group. The nutritional protocol implementation led to an increase in caloric intake (1070 vs. 1357 kcal/day, p = 0.018) and in the percentage of days within 80-100% of the energy target (11 vs. 20%, p = 0.021). The protein debt decreased significantly from 48 g/day to 37 g/day (p = 0.015). No significant difference in the percentage of days within the protein target (80-100%) was observed. CONCLUSIONS: Calorie and protein coverage improved after the implementation of the simplified nutritional protocol in critically ill COVID-19 patients. Further studies are needed to assess the impact of such an approach on patients' clinical outcomes.

Adapting to the unexpected: Problematic work situations and resilience strategies in healthcare institutions during the COVID-19 pandemic's first wave.

The COVID-19 pandemic's first wave required considerable adaptation efforts on the part of healthcare workers. The literature on resilient healthcare describes how the collective regulation strategies implemented by frontline employees make essential contributions to institutions' abilities to cope with major crises. The present mixed-methodology study was thus conducted among a large sample of employees in a variety of Swiss healthcare institutions and focused on problematic real-world situations experienced by them and their managers during the pandemic's first wave. It highlighted the anticipatory and adaptive strategies implemented by institutions, teams and individuals. The most frequently cited problematic situations involved organisational changes, interpersonal conflicts and workloads. In addition to the numerous top-down measures implemented by institutions, respondents also identified personal or team regulation strategies such as increasing staff flexibility, prioritising tasks, interprofessional collaboration, peer support or creating new communication channels to families. The present findings underlined the importance of taking greater account of healthcare support staff and strengthening managerial capacity to support interprofessional teams including those support staff.