Immediate Clinical Complications Occurring During Membrane Change in Patients on Veno-Venous Extracorporeal Membrane Oxygenation.

The clinical tolerance of extracorporeal membrane oxygenation (ECMO) membrane changes in acute respiratory distress syndrome (ARDS) patients under veno-venous ECMO (VV-ECMO) has not been reported. The aim of this study was to describe the tolerance of membrane change. Patients requiring VV-ECMO were retrospectively included between March 2020 and May 2022. In case of membrane dysfunction or an increase in hemolysis markers or an alteration in gas exchange, a membrane change was performed. The primary outcome was a composite measure defined as the occurrence of at least one of the following events within 1 hour of membrane change: severe hypoxemia, hemodynamic collapse, bradycardia, arrhythmia, cardiac arrest, and death. During the study period, 70 patients required a VV-ECMO, 29 (41%) of whom died. Thirty-two patients required a membrane change for a total of 56 changes. The primary outcome occurred for 33 (59%) changes. Arterial desaturation <80% occurred for all complicated membrane changes and cardiac arrest concerned nine changes (16%). Low tidal volume (VT), respiratory system compliance (Crs), PaO2, and high ECMO blood flow (QECMO) were associated with poor tolerance of membrane change. Threshold values of 130 ml for VT, 9.3 cm H2O for Crs, 72 mm Hg for PaO2, and 3.65 L/minute for QECMO best determined the risk of poor tolerance of membrane change.

End-tidal carbon dioxide during spontaneous breathing trial to predict extubation failure: A prospective observational study.

Despite advances in weaning protocols, extubation failure (EF) is associated with poor outcomes. Many predictors of EF have been proposed, including hypercapnia at the end of the spontaneous breathing test (SBT). However, performing arterial blood gases at the end of SBT is not routinely recommended, whereas end-tidal carbon dioxide (EtCO2) can be routinely monitored during SBT. We aimed to evaluate the clinical utility of EtCO2 to predict EF. Patients undergoing planned extubation were eligible. Non-inclusion criteria were tracheostomy and patients extubated after successful T-tube SBT. We recorded clinical data and EtCO2 in 189 patients during a successful one-hour low pressure support SBT. EtCO2 measured before successful SBT was lower in patients with EF compared to those with successful extubation (27 [24-29] vs 30 [27-47] mmHg, p = 0.02), while EtCO2 measured at five minutes and at the end of the SBT was not different between the two groups (26 [22-28] vs. 29 [28-49] mmHg, p = 0.06 and 26 [26-29] vs. 29 [27-49] mmHg, p = 0.09, respectively). Variables identified by multivariable analysis as independently associated with EF were acute respiratory failure as the cause of intubation and ineffective cough. Our study suggests that recording EtCO2 during successful SBT appears to have limited predictive value for EF.

Hematological features and alternate diagnoses in critically ill thrombotic antiphospholipid syndrome patients.

OBJECTIVES: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome. METHODS: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied. RESULTS: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients. CONCLUSION: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated.

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum ß-lactamase-producing Enterobacterales rectal carriage.

BACKGROUND: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. METHODS: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. RESULTS: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1-35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6-22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5-22.1), p = 0.01). CONCLUSION: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024.

BACKGROUND: A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. METHODS: The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). RESULTS: During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). CONCLUSIONS: Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Community-acquired Klebsiella pneumoniae pneumonia in ICU: a multicenter retrospective study.

BACKGROUND: Alongside the recent worldwide expansion of hypervirulent Klebsiella pneumoniae (KP) infections, the available literature regarding cases of community acquired pneumonias (KP-CAP) remains scarce but reports a strikingly high and early mortality. We performed a retrospective multicenter study (7 ICU in France) between 2015 and 2019, comparing prognosis and severity of KP-CAP versus Streptococcus pneumoniae - CAP (SP-CAP). METHODS: For each KP-CAP, three SP-CAP admitted in ICUs within the same center and within the same 6-month window were selected. When available, KP strains were studied, and bacterial virulence was genetically assessed for virulence factors. The primary outcome was in-hospital mortality. Associations between clinical outcomes and type of infection were tested using univariate and multivariate logistic regressions, adjusted for pairing variables. RESULTS: Twenty-seven KP-CAP and 81 SP-CAP were included. Respective in-hospital mortality rates were 59% (n = 16) and 17% (n = 14, p < 0.001), despite adequate antibiotic therapy. KP-CAP median time from admission to death was 26.9 h [IQR 5.75-44 h] and were significantly associated with higher rates of multiple organ failures (93% vs. 42%, p < 0.001), disseminated intravascular coagulation (12% vs. 1.3%, p = 0.046), septic shock (median lactate on ICU admission 4.60 vs. 2.90 mmol/L, p = 0.030) and kidney failure (KDIGO-3: 87% vs. 44%, p < 0.001). Interestingly, alcoholism was the only identified predisposing factor of KP-CAP. Severity on ICU admission (2-fold higher for KP-CAP) was the only factor associated with mortality in a multivariate analysis. CONCLUSION: We described a strong association between KP-CAP infection and higher and earlier mortality when compared to SP-CAP. Moreover, alcoholism was the sole predisposing factor associated with KP-CAP infection. These findings should raise awareness of clinicians involved in the management of severe CAP about this microbiological etiology. Future prospective studies are needed to confirm these results and to design strategies to improve the prognosis of such infections.

Regional pulmonary perfusion, blood volume, and their relationship change in experimental early ARDS.

Regional pulmonary perfusion (Q) has been investigated using blood volume (Fb) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and Fb differently. Five sheep were anesthetized and received lung protective mechanical ventilation for 20 h while endotoxin was continuously infused. Using dynamic 18F-FDG and 13NN Positron Emission Tomography (PET), regional Fb and Q were analysed in 30 regions of interest (ROIs) and normalized by tissue content (Fbn and Qn, respectively). After 20 h, the lung injury showed characteristics of early ARDS, including gas exchange and lung mechanics. PET images of Fbn and Qn showed substantial differences between baseline and lung injury. Lung injury caused a significant change in the Fbn-Qn relationship compared to baseline (p < 0.001). The best models at baseline and lung injury were Fbn = 0.32 + 0.690Qn and Fbn = 1.684Qn-0.538Qn2, respectively. Endotoxine-associated early ARDS changed the relationship between Fb and Q, shifting from linear to curvilinear. Effects of endotoxin exposure on the vasoactive blood flow regulation were most likely the key factor for this change limiting the quantitative accuracy of Fb imaging as a surrogate for regional Q.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

PURPOSE: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. METHODS: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization. RESULTS: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. CONCLUSION: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Low-flow ECCO2R conjoined with renal replacement therapy platform to manage pulmonary vascular dysfunction with refractory hypercapnia in ARDS.

Background: Hypercapnia worsens lung vascular dysfunction during acute respiratory distress syndrome (ARDS). We tested whether an extracorporeal carbon dioxide removal (ECCO2R) device based on a renal replacement therapy platform (Prismalung®) may reduce PaCO2 and alleviate lung vascular dysfunction in ARDS patients with refractory hypercapnia. Methods: We planned to prospectively include 20 patients with moderate-to-severe ARDS, pulmonary vascular dysfunction on echocardiography, and PaCO2 ≥ 48 mmHg despite instrumental dead space reduction and the increase in respiratory rate. Hemodynamics, echocardiography, respiratory mechanics, and arterial blood gases were recorded at 2 (H2), 6 (H6) and 24 (H24) hours as ECCO2R treatment was continued for at least 24 h. Results: Only eight patients were included, and the study was stopped due to worldwide shortage of ECCO2R membranes and the pandemic. Only one patient fulfilled the primary endpoint criterion (decrease in PaCO2 of more than 20 %) at H2, but this objective was achieved in half of patients (n = 4) at H6. The percentage of patients with a PaCO2 value < 48 mmHg increased with time, from 0/8 (0 %) at H0, to 3/8 (37.5 %) at H2 and 4/8 (50 %) at H6 (p = 0.04). There was no major change in hemodynamic and echocardiographic variables with ECCO2R, except for a significant decrease in heart rate. ECCO2R was prematurely discontinued before H24 in five (62.5 %) patients, due to membrane clotting in all cases. Conclusions: This pilot study testing showed a narrow efficacy and high rate of membrane thrombosis with the first version of the system. Improved versions should be tested in future trials. Trial registration: Registered at clinicaltrials.gov, identifier: NCT03303807, Registered: October 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03303807.

Clinical Phenotypes and Molecular Characteristics of Respiratory Syncytial Virus in Adults: A Monocentric Prospective Study Between 2019 and 2022.

Respiratory syncytial virus (RSV) infection is a major cause of pneumonia in adults. Little is known on the viral genetic diversity and the associated clinical phenotypes in this population. This single-center prospective cohort study included RSV-infected patients hospitalized between January 2019 and December 2022. Of 100 patients, including 41 with severe infection, 72 were infected with RSV-B. RSV genome sequencing showed no clustering according to severity. Patients infected with RSV-B with risk factors for severe pneumonia had significantly higher fusion protein diversity scores. No amino acid substitutions conferring resistance to nirsevimab were detected.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study.

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? STUDY DESIGN AND METHODS: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in critically ill COVID-19 patients.

Severe coronavirus disease 2019 (COVID-19) is related to dysregulated immune responses. We aimed to explore the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on the immune response by nasopharyngeal transcriptomic in critically-ill patients. This prospective monocentric study included COVID-19 patients requiring intensive care unit (ICU) admission between March 2020 and 2022. Patients were classified according to VOC (ancestral, Alpha, Delta, and Omicron). Eighty-eight patients with severe COVID-19 were included after matching (on prespecified clinical criteria). Profiling of gene expression markers of innate and adaptive immune responses were investigated by respiratory transcriptomics at ICU admission. Eighty-eight patients were included in the study after matching (ancestral [n = 24], Alpha [n = 24], Delta [n = 22], and Omicron [n = 18] variants). Respiratory transcriptomic analysis revealed distinct innate and adaptive immune profiling between variants. In comparison with the ancestral variant, there was a reduced expression of neutrophil degranulation, T cell activation, cytokines signalling pathways in patients infected with Alpha and Delta variants. In contrast, there was a higher expression of neutrophil degranulation, T and B cells activation, and inflammatory interleukins pathways in patients infected with Omicron. To conclude, Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in patients with severe COVID-19, pointing to an evolving pathophysiology of severe COVID-19 in the Omicron era.

Chest Computed Tomography Characteristics of Critically Ill COVID-19 Patients with Auto-antibodies Against Type I Interferons.

PURPOSE: Patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. METHODS: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. RESULTS: Two hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8) versus 24.0 (19.0-30.0), p = 0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175). CONCLUSION: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.