Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients.

Background: Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors. Methods: We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals. Results: Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality. Conclusion: We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.

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.

Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients

Background Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors. Methods We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals. Results Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality. Conclusion We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.

Implementation of a Novel Concept of Emergency Department Management: e-Boss.

Hospital-based emergency services are frequently criticized worldwide for their management, which can lead to a decrease in staff motivation, with a potential impact on patient safety. This article describes how harnessing the power of social networks can facilitate the management of emergency department teams. Beyond teaching, promoting emergency medicine and recruiting health professionals, these tools can unite employees around a virtual leader and help develop a true service culture. The concept of management through social networks is a novel manner to reach out to staff and should be further explored for use in the health care context.

A pilot clinical and radiographic study on the association between periodontitis and serious COVID-19 infection.

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.

Blood Transfusion Reactions-A Comprehensive Review of the Literature including a Swiss Perspective.

Blood transfusions have been the cornerstone of life support since the introduction of the ABO classification in the 20th century. The physiologic goal is to restore adequate tissue oxygenation when the demand exceeds the offer. Although it can be a life-saving therapy, blood transfusions can lead to serious adverse effects, and it is essential that physicians remain up to date with the current literature and are aware of the pathophysiology, initial management and risks of each type of transfusion reaction. We aim to provide a structured overview of the pathophysiology, clinical presentation, diagnostic approach and management of acute transfusion reactions based on the literature available in 2022. The numbers of blood transfusions, transfusion reactions and the reporting rate of transfusion reactions differ between countries in Europe. The most frequent transfusion reactions in 2020 were alloimmunizations, febrile non-hemolytic transfusion reactions and allergic transfusion reactions. Transfusion-related acute lung injury, transfusion-associated circulatory overload and septic transfusion reactions were less frequent. Furthermore, the COVID-19 pandemic has challenged the healthcare system with decreasing blood donations and blood supplies, as well as rising concerns within the medical community but also in patients about blood safety and transfusion reactions in COVID-19 patients. The best way to prevent transfusion reactions is to avoid unnecessary blood transfusions and maintain a transfusion-restrictive strategy. Any symptom occurring within 24 h of a blood transfusion should be considered a transfusion reaction and referred to the hemovigilance reporting system. The initial management of blood transfusion reactions requires early identification, immediate interruption of the transfusion, early consultation of the hematologic and ICU departments and fluid resuscitation.

Blood Transfusion Reactions-A Comprehensive Review of the Literature including a Swiss Perspective

Blood transfusions have been the cornerstone of life support since the introduction of the ABO classification in the 20th century. The physiologic goal is to restore adequate tissue oxygenation when the demand exceeds the offer. Although it can be a life-saving therapy, blood transfusions can lead to serious adverse effects, and it is essential that physicians remain up to date with the current literature and are aware of the pathophysiology, initial management and risks of each type of transfusion reaction. We aim to provide a structured overview of the pathophysiology, clinical presentation, diagnostic approach and management of acute transfusion reactions based on the literature available in 2022. The numbers of blood transfusions, transfusion reactions and the reporting rate of transfusion reactions differ between countries in Europe. The most frequent transfusion reactions in 2020 were alloimmunizations, febrile non-hemolytic transfusion reactions and allergic transfusion reactions. Transfusion-related acute lung injury, transfusion-associated circulatory overload and septic transfusion reactions were less frequent. Furthermore, the COVID-19 pandemic has challenged the healthcare system with decreasing blood donations and blood supplies, as well as rising concerns within the medical community but also in patients about blood safety and transfusion reactions in COVID-19 patients. The best way to prevent transfusion reactions is to avoid unnecessary blood transfusions and maintain a transfusion-restrictive strategy. Any symptom occurring within 24 h of a blood transfusion should be considered a transfusion reaction and referred to the hemovigilance reporting system. The initial management of blood transfusion reactions requires early identification, immediate interruption of the transfusion, early consultation of the hematologic and ICU departments and fluid resuscitation.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Associated with COVID-19: An Emulated Target Trial Analysis.

Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0-9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, -2%; 95% confidence interval, -10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.

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.

SARS-CoV-2 infection as a trigger of humoral response against apolipoprotein A-1.

BACKGROUND: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes. DESIGN: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period. RESULTS: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004). CONCLUSION: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

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.

Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients.

OBJECTIVES: In many countries, large numbers of critically ill patients with coronavirus disease 2019 are admitted to the ICUs within a short period of time, overwhelming usual care capacities. Preparedness and reorganization ahead of the wave to increase ICU surge capacity may be associated with favorable outcome. The purpose of this study was to report our experience in terms of ICU organization and anticipation, as well as reporting patient characteristics, treatment, and outcomes. DESIGN: A prospective observational study. SETTING: The division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). PATIENTS: All consecutive adult patients with acute respiratory failure due to coronavirus disease 2019 admitted in the ICU between March 9, 2020, and May 19, 2020, were enrolled. Patients' demographic data, comorbidities, laboratory values, treatments, and clinical outcomes were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ICU was reorganized into cells of six to eight patients under the care of three physicians and five nurses. Its capacity increased from 30 to 110 beds, fully equipped and staffed, transforming the surgical intermediate care unit, the postoperative care facility, and operating theaters into ICUs. Surge capacity has always exceeded the number of patients hospitalized. Among 129 critically ill patients with severe acute hypoxemic respiratory failure, 96% required invasive mechanical ventilation. A total of 105 patients (81%) were discharged alive and 24 died, corresponding to a mortality of 19%. Patients who died were significantly older, with higher severity scores at admission, had higher levels of d-dimers, plasma creatinine, high-sensitive troponin T, C-reactive protein, and procalcitonin, and required more frequent prone sessions. CONCLUSIONS: A rapid increase in ICU bed capacity, including adequate equipment and staffing, allowed for a large number of critically ill coronavirus disease 2019 patients to be taken care of within a short period of time. Anticipation and preparedness ahead of the wave may account for the low mortality observed in our center. These results highlight the importance of resources management strategy in the context of the ongoing coronavirus disease 2019 pandemic.