Delirium in Adults With COVID-19-related ARDS: Comparison With Other Etiologies.

BACKGROUND AND OBJECTIVES: Neurological complications have been associated with COVID-19, including deliriumSuch complications have been reported to be frequent among ICU admitted patients. We hypothesized that the rate of neurological complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. METHODS: We conducted a retrospective cohort study in the adult intensive care unit (ICU) of our hospital, including all consecutive patients fulfilling Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurological complications of the central (stroke, hemmorhage, vasculitis) or critical illness weakness, and 30 and 180 days all-cause mortality. RESULTS: 311 patients were included in the study (253 with COVID-19 and 58 with other causes); CAM-ICU was assessed in 231 (74.3% in COVID-19 vs. 74,1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison(69.1% vs 60.5%, P=0.246). Yet, COVID-19 patients had higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol, dexmedetomidine). After adjusting for these factors in COVID-19 patients in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted odds ratio (OR) (95% CI): 0.86 (0.35-2.1)). Similarly, COVID-19 related ARDS had no impact on all-cause mortality at 30 days (adjusted OR: 0.87 (0.39-1.92)) and 180 days (adjusted OR: 0.67 (0.33-1.35)). Finally, neurological complications affecting the central nervous system (adjusted OR: 1.15 (0.25-5.29)) and critical illness weakness (adjusted OR: 2.99 (0.97-9.1)) were not higher in the COVID-19 group.Discussion: Compared to other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurological complications, after accounting for underlying disease severity in ARDS patients. Management of COVID-19 associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.

Response to the first awake prone positioning relates with intubation rate in SARS-CoV-2 patients suffering from acute respiratory failure with moderate to severe hypoxaemia: a retrospective study.

AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a "do not intubate order", 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001). CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.

The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients.

The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a 'discovery' cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P < 0.05 to P < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two 'validation' cohorts, i.e. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.

Postmortem Cardiopulmonary Pathology in Patients with COVID-19 Infection: Single-Center Report of 12 Autopsies from Lausanne, Switzerland.

We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35-96) died 6-38 days after onset of symptoms (median: 14.5 days). Eight patients received mechanical ventilation. Ten patients showed diffuse alveolar damage (DAD), 7 as exudative and 3 as proliferative/organizing DAD. One case presented as acute fibrinous and organizing pneumonia. Seven patients (58%) had acute bronchopneumonia, 1/7 without associated DAD and 1/7 with aspergillosis and necrotic bronchitis. Microthrombi were present in 5 patients, only in exudative DAD. Reverse transcriptase quantitative PCR detected high virus amounts in 6 patients (50%) with exudative DAD and symptom-duration ≤14 days, supported by immunohistochemistry and in-situ RNA hybridization (RNAscope). The 6 patients with low viral copy levels were symptomatic for ≥15 days, comprising all cases with organizing DAD, the patient without DAD and one exudative DAD. We show the high prevalence of DAD as a reaction pattern in COVID-19, the high number of overlying acute bronchopneumonia, and high-level pulmonary virus detection limited to patients who died ≤2 weeks after onset of symptoms, correlating with exudative phase of DAD.

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.

Multisystem inflammatory syndrome with refractory cardiogenic shock due to acute myocarditis and mononeuritis multiplex after SARS-CoV-2 infection in an adult.

A 22-year-old male with a typical history of pauci-symptomatic COVID-19 3 weeks earlier, confirmed by positive serology for SARS-CoV-2 (IgG), was admitted to the intensive care unit because of severe myocarditis with refractory cardiogenic shock that required extracorporeal life support. Due to a clinical presentation suggestive of Kawasaki-like disease with coronary aneurysm and severe systemic inflammation, intravenous immunoglobulins were administered in combination with tocilizumab. The initial clinical course was favourable with these treatments. However, the patient subsequently developed a severe mononeuritis multiplex leading to bilateral foot drop, which required intensive immunosuppressive therapy (corticosteroids, cyclophosphamide and rituximab). The clinical presentation meets the criteria for multisystem inflammatory syndrome associated with SARS-CoV-2, but includes very severe organ damages. Early recognition, a multidisciplinary approach and aggressive therapeutic intervention can lead to a favourable outcome.