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.

Stability of Drugs Stored in Helicopters for Use by Emergency Medical Services: A Prospective Observational Study.

STUDY OBJECTIVE: Drugs stored in rescue helicopters may be subject to extreme environmental conditions. The aim of this study was to measure whether drugs stored under the real-life conditions of a Swiss helicopter emergency medical service (HEMS) would retain their potency over the course of 1 year. METHODS: A prospective, longitudinal study measuring the temperature exposure and concentration of drugs stored on 2 rescue helicopters in Switzerland over 1 year. The study drugs included epinephrine, norepinephrine, amiodarone, midazolam, fentanyl, naloxone, rocuronium, etomidate, and ketamine. Temperatures were measured inside the medication storage bags and the crew cabins at 10-minute intervals. Drug stability was measured on a monthly basis over the course of 12 months using high-performance liquid chromatography. The medications were considered stable at a minimum remaining drug concentration of 90% of the label claim. RESULTS: Temperatures ranged from -1.2 °C to 38.1 °C (29.84 °F to 100.58 °F) inside the drug storage bags. Of all the temperature measurements inside the drug storage bags, 37% lay outside the recommended storage conditions. All drugs maintained a concentration above 90% of the label claim. The observation periods for rocuronium and etomidate were shortened to 7 months because of a supply shortage of reference samples. CONCLUSION: Drugs stored under the real-life conditions of Swiss HEMS are subjected to temperatures outside the manufacturer's approved storage requirements. Despite this, all drugs stored under these conditions remained stable throughout our study. Real-life stability testing could be a way to extend drug exchange intervals.

Critical care staffing ratio and outcome of COVID-19 patients requiring intensive care unit admission during the first pandemic wave: a retrospective analysis across Switzerland from the RISC-19-ICU observational cohort.

STUDY AIM: The surge of admissions due to severe COVID-19 increased the patients-to-critical care staffing ratio within the ICUs. We investigated whether the daily level of staffing was associated with an increased risk of ICU mortality (primary endpoint), length of stay (LOS), mechanical ventilation and the evolution of disease (secondary endpoints). METHODS: We employed a retrospective multicentre analysis of the international Risk Stratification in COVID-19 patients in the ICU (RISC-19-ICU) registry, limited to the period between March 1 and May 31, 2020, and to Switzerland. Hierarchical regression models were used to investigate crude and adjusted effects of the critical care staffing ratio on study endpoints. We adjusted for disease severity and weekly caseload. RESULTS: Among the 38 participating Swiss ICUs, 17 recorded staffing information. The study population included 437 patients and 2,342 daily assessments of patient-to-critical care staffing ratio. Median of daily patient-to-nurse ratio started at 1.0 [IQR 0.5-1.5; calendar week 9] and peaked at 2.4 (IQR 0.4-2.0; calendar week 16), while the median of daily patient-to-physician ratio started at 4.0 (IQR 2.1-5.0; calendar week 9) and peaked at 6.8 (IQR 6.3-7.3; calendar week 19). Neither the patient-to-nurse (adjusted OR 1.28, 95% CI 0.85-1.93; doubling of ratio) nor the patient-to-physician ratio (adjusted OR 1.07, 95% CI 0.87-1.32; doubling of ratio) were associated with ICU mortality. We found no association of daily critical care staffing on the secondary endpoints in adjusted models. CONCLUSION: We found no association of reduced availability of critical care staffing resources in Swiss ICUs with overall ICU length of stay nor mortality. Whether long-term outcome of critically ill patients with COVID-19 have been affected remains to be studied.

Pre-hospital care & interfacility transport of 385 COVID-19 emergency patients: an air ambulance perspective.

BACKGROUND: COVID-19, the pandemic caused by the severe acute respiratory syndrome coronavirus-2, is challenging healthcare systems worldwide. Little is known about problems faced by emergency medical services-particularly helicopter services-caring for suspected or confirmed COVID-19 patients. We aimed to describe the issues faced by air ambulance services in Europe as they transport potential COVID-19 patients. METHODS: Nine different HEMS providers in seven different countries across Europe were invited to share their experiences and to report their data regarding the care, transport, and safety measures in suspected or confirmed COVID-19 missions. Six air ambulance providers in six countries agreed and reported their data regarding development of special procedures and safety instructions in preparation for the COVID-19 pandemic. Four providers agreed to provide mission related data. Three hundred eighty-five COVID-19-related missions were analysed, including 119 primary transport missions and 266 interfacility transport missions. RESULTS: All providers had developed special procedures and safety instructions in preparation for COVID-19. Ground transport was the preferred mode of transport in primary missions, whereas air transport was preferred for interfacility transport. In some countries the transport of COVID-19 patients by regular air ambulance services was avoided. Patients in interfacility transport missions had a significantly higher median (range) NACA Score 4 (2-5) compared with 3 (1-7), needed significantly more medical interventions, were significantly younger (59.6 ± 16 vs 65 ± 21 years), and were significantly more often male (73% vs 60.5%). CONCLUSIONS: All participating air ambulance providers were prepared for COVID-19. Safe care and transport of suspected or confirmed COVID-19 patients is achievable. Most patients on primary missions were transported by ground. These patients were less sick than interfacility transport patients, for whom air transport was the preferred method.

Transport of COVID-19 and other highly contagious patients by helicopter and fixed-wing air ambulance: a narrative review and experience of the Swiss air rescue Rega

BackgroundThe current COVID-19 pandemic highlights the challenges air ambulance services are facing when transporting highly infectious patients for several hours in enclosed spaces. This overview provides an example of a standard operating procedure (SOP) for infection prevention measures in HEMS missions during the COVID-19 pandemic. Furthermore, we describe different methods used by several organizations in Europe and the experience of the Swiss air rescue organization Rega in transporting these patients.Possible benefits of the use of small patient isolation units (PIU) are discussed, including the fact that accompanying medical personnel do not need to wear personal protective equipment (PPE) during the transport but can still maintain full access to the patient. Rega has developed and patented its own PIU. This device allows spontaneously breathing or mechanically ventilated patients to be transported in pressurized jet cabins, small helicopters and ambulance vehicles, without the need to change between transport units. This PIU is unique, as it remains air-tight even when there is a sudden loss of cabin pressure.ConclusionA wide variety of means are being used for the aeromedical transport of infectious patients. These involve isolating either the patient or the medical crew. One benefit of PIUs is that the means of transport can be easily changed without contaminating the surroundings and while still allowing access to the patient.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Clinical and Imaging Features of COVID-19-Associated Pulmonary Aspergillosis.

BACKGROUND: COVID-19 superinfection by Aspergillus (COVID-19-associated aspergillosis, CAPA) is increasingly observed due to increased awareness and use of corticosteroids. The aim of this study is to compare clinical and imaging features between COVID-19 patients with and without associated pulmonary aspergillosis. MATERIAL AND METHODS: In this case-control study, hospitalized patients between March 2020 and March 2021 were evaluated. Two observers independently compared 105 chest CTs of 52 COVID-19 patients without pulmonary aspergillosis to 40 chest CTs of 13 CAPA patients. The following features were evaluated: lung involvement, predominant main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings. Chronological changes in the abnormal extent upon CT and chronological changes in the main patterns were compared with mixed models. Patient-wise comparisons of additional features and demographic and clinical data were performed using Student's t-test, Chi-squared test, Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: Compared to COVID-19 patients without pulmonary aspergillosis, CAPA patients were older (mean age (±SD): 70.3 (±7.8) versus 63.5 (±9.5) years (p = 0.01). The time-dependent evolution rates for consolidation (p = 0.02) and ground glass (p = 0.006) differed. In early COVID-19 disease, consolidation was associated with CAPA, whereas ground glass was less common. Chronological changes in the abnormal extent upon CT did not differ (p = 0.29). Regardless of the time point, bronchial wall thickening was observed more frequently in CAPA patients (p = 0.03). CONCLUSIONS: CAPA patients showed a tendency for consolidation in early COVID-19 disease. Bronchial wall thickening and higher patient age were associated with CAPA. The overall lung involvement was similar between both groups.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.