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Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron ( n  = 148) is different from that in those infected with variant Delta ( n  = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p  = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p  = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 ( n  = 109) and BA.2 ( n  = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality. SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.

Introduction: Aim of this study is to analyse the characteristics of ventilator-associated pneumonia (VAP) inpatients infected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Materials and Methods: A retrospective study was conducted, including coronavirus infectious disease 2019 (COVID-19) patients who developed VAP from March to May 2020 (VAP COVID-19). They were compared to non-COVID-19 patients who developed VAP from January 2011 to December 2019 (VAP NO COVID-19) and COVID-19 patients who did not develop VAP (NO VAP COVID-19). Results: Overall, 42 patients were included in the VAP COVID-19group, 37 in the NO VAP COVID-19 group, and 188 in the VAP NO COVID-19 group. VAP COVID-19 had significantly higher rates of shock (71% vs. 48%, p = 0.009), death in ICU (52% vs. 30%, p = 0.011), VAP recurrence (28% vs. 4%, p < 0.0001), positive blood culture (26% vs. 13%, p = 0.038), and polymicrobial culture (28% vs. 13%, p = 0.011) than VAP NO COVID-19. At the multivariate analysis, death in patients with VAP was associated with shock (p = 0.032) and SARS-CoV-2 (p = 0.008) infection. Conclusions: VAP in COVID-19 patients is associated with shock, bloodstream, and polymicrobial infections.

Background Severe COVID-19 is associated with dysregulated immune responses. Immune responses heterogeneity was previously reported during the first waves of the pandemic. We aimed to characterise mucosal transcriptomic profiles in critically-ill patients during the Omicron era. Methods This prospective multicentre study included 94 critically-ill COVID-19 patients between May 2022 and August 2023. Upper respiratory tract mucosal transcriptomes were obtained from nasopharyngeal swabs and clustered based on KEGG cytokine-cytokine receptor interaction pathways using an unsupervised algorithm. Differential transcript expression, cell population abundance and gene set enrichment analyses were performed. Results Here we show that in 56 critically ill COVID-19 patients, transcriptomic clustering reveals two distinct COVID-19 Immune Transcriptomic Respiratory Profiles (CITRP), including CITRP-1 and CITRP-2, characterised by differential expression of cytokine and immune response pathways. Patients in the CITRP-2 group display a more pronounced immune and inflammatory response, involving specific innate immune pathways, neutrophil degranulation and T-helper 2 cytokines (e.g., IL-1, IL-4 and IL-13), and a significantly higher proportion of neutrophils than patients in the CITRP-1 group. No significant differences are observed between the two transcriptomic clusters in clinical, biological and virological characteristics at ICU admission or in patient outcomes. Conclusions This study highlights the heterogeneity of the immune response in critically-ill COVID-19 patients in the Omicron era, identifies two endotypes from the analysis of upper airway mucosal transcriptomics. Our findings suggest the existence of two distinct pathogenic mechanisms and the detrimental role of neutrophil and Th2 helper cell-mediated inflammation in a subset of patients with severe disease. They support the need for personalised treatment strategies targeting neutrophil-mediated lung damage and/or specific cytokine production in a subset of critically-ill COVID-19 patients. Plain language summary Severe forms of COVID-19 are associated with an immune response that behaves irregularly. While previous studies have demonstrated that this response can vary significantly between patients, most of this research was conducted prior to the emergence of the Omicron variant. The aim of this study was to explore whether this diversity in immune responses also exists in critically ill patients infected with Omicron. We analysed the immune systems in samples taken from the upper airways of critically ill patients and grouped them based on similarities in their immune response. Two distinct categories of immune response were identified. One group showed a stronger immune response and more inflammation, but no clear differences were observed in how symptoms or disease progression presented between the two groups. These findings emphasise the diversity of immune responses in critically ill patients infected with the Omicron variant, highlighting the need for more personalised treatment strategies. Bay et al. investigate upper respiratory mucosal transcriptomic profiles in critically ill COVID-19 patients infected with Omicron using an unsupervised clustering approach. Their study identifies two distinct immune response profiles, one characterised by enhanced innate and inflammatory activation compared with the other, highlighting the immune heterogeneity in severe COVID-19.

BackgroundDespite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality.ResultsThe study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up.ConclusionsCritically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.

IntroductionNon-invasive ventilation (NIV) is recommended as first-line therapy in respiratory failure of critically ill immunocompromised patients as it can decrease intubation and mortality rates as compared with standard oxygen. However, its recommendation is only conditional. Indeed, the use of NIV in this setting has been challenged recently based on results of trials finding similar outcomes with or without NIV or even deleterious effects of NIV. To date, NIV has been compared with standard oxygen but not to high-flow nasal oxygen therapy (HFOT) in immunocompromised patients. Several studies have found lower mortality rates using HFOT alone than when using HFOT with NIV sessions in patients with de novo respiratory failure, and even in immunocompromised patients. We are hypothesising that HFOT alone is more effective than HFOT with NIV sessions and reduces mortality of immunocompromised patients with acute hypoxemic respiratory failure.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing HFOT alone or with NIV in immunocompromised patients admitted to intensive care unit (ICU) for severe acute hypoxemic respiratory failure. Around 280 patients will be randomised with a 1:1 ratio in two groups. The primary outcome is the mortality rate at day 28 after inclusion. Secondary outcomes include the rate of intubation in each group, length of ICU and hospital stay and mortality up to day 180.Ethics and disseminationThe study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT02978300

Pulmonary embolism (PE) remains a frequent and potentially fatal condition, with early mortality largely driven by (RV) failure and hemodynamic collapse. Rapid and accurate prognostic assessment is therefore central to management. Current European Society of Cardiology (ESC) strategies rely first on hemodynamic status to identify high-risk patients requiring urgent reperfusion consideration, and then—when patients are normotensive—on a stepwise approach combining clinical risk scores, RV imaging, and circulating biomarkers. Clinical tools such as HESTIA and the Pulmonary Embolism Severity Index (PESI)/simplified PESI (sPESI) enable early identification of low-risk patients suitable for outpatient pathways and stratify 30-day mortality risk, but do not integrate biological data. Consequently, biomarkers have an expanding role in refining prognosis, particularly within the heterogeneous intermediate-risk group. This review provides a practical overview of established and emerging biomarkers for PE risk stratification. Conventional cardiac biomarkers—troponins and natriuretic peptides (BNP/NT-proBNP)—reflect RV myocardial injury and strain and, when combined with imaging evidence of RV dysfunction, allow discrimination between intermediate–low- and intermediate–high-risk PE, guiding monitoring intensity and escalation strategies. D-dimer, while essential in diagnostic algorithms because of its high negative predictive value, has only an adjunctive and indirect prognostic role. Beyond these markers, growing evidence supports additional biomarkers capturing complementary pathways: neurohormonal stress (copeptin), early myocardial injury (H-FABP), inflammation and hypoxia (GDF-15), tissue hypoperfusion (lactate), and molecular regulation (circulating microRNAs). Readily available inflammatory indices derived from blood counts (NLR, PLR, LMR), red cell distribution width, and hs-CRP may further contribute within multimarker models, although specificity and validation remain limitations. Future directions include multimodal and omics-driven biomarker profiling integrated with advanced imaging to enable more precise, dynamic, and personalized PE care, from acute risk prediction to long-term follow-up and prevention of chronic thromboembolic complications.

Background The lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario. We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others. Methods We conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France. We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support. Results A total of 508 patients were admitted with suspected septic shock. Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset. Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay. There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support. The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock. A sensitivity analysis was performed in the subgroup ( n  = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results. Conclusions One quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker. Outcome did not differ between patients with early-confirmed septic shock and other patients.

PurposeData on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality.MethodsA 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up).ResultsAmong the 306 included patients, 126 (41.2%; 95% CI 35.6–46.9) died and 180 (58.8%; 95% CI 53.3–64.3) survived during the follow-up period [13 (3–24) days], including 51/180 patients (28.3%, 95% CI 21.9–35.5) who eventually required limb amputations, with a median number of 3 (1–4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR) = 1.03 (1.02–1.04); p < 0.001], lower leucocytes [HR 0.83 (0.69–0.99); p = 0.034] and platelet counts [HR 0.77 (0.60–0.91); p = 0.007], and arterial blood lactate levels [HR 2.71 (1.68–4.38); p < 0.001] were independently associated with hospital death, while a neck stiffness [HR 0.51 (0.28–0.92); p = 0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06–3.38); p = 0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis.ConclusionPurpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation.Trials registrationNCT03216577.

Objectives Our objectives were (1) to characterize the distribution of serum potassium levels at ICU admission, (2) to examine the relationship between dyskalemia at ICU admission and occurrence of cardiac events, and (3) to study both the association between dyskalemia at ICU admission and dyskalemia correction by day 2 on 28-day mortality. Design Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1999–2014) Setting 22 French OUTCOMEREA network ICUs Patients Patients were classified into six groups according to their serum potassium level at admission: three groups of hypokalemia and three groups of hyperkalemia defined as serious hypokalemia [K+] < 2.5 and serious hyperkalemia [K+] > 7 mmol/L, moderate hypokalemia 2.5 ≤ [K+] < 3 mmol/L and moderate hyperkalemia 6 < [K+] ≤ 7 mmol/L, and mild hypokalemia 3 ≤ [K+] < 3.5 mmol/L and mild hyperkalemia 5 < [K+] ≤ 6 mmol/L. We sorted evolution at day 2 of dyskalemia into three categories: balanced, not-balanced, and overbalanced. Intervention None Measurements and main results Of 12,090 patients, 2108 (17.4%) had hypokalemia and 1445 (12%) had hyperkalemia. Prognostic impact of dyskalemia and its correction was assessed using multivariate Cox models. After adjustment, hypokalemia and hyperkalemia were independently associated with a greater risk of 28-day mortality. Mild hyperkalemic patients had the highest mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) [1.13–1.47], p  < 0.001). Adjusted 28-day mortality was higher if serum potassium level was not-balanced at day 2 (aHR = 1.51, 95% CI [1.30–1.76], p  < 0.0001) and numerically higher but not significantly different if serum potassium level was overbalanced at day 2 (aHR = 1.157, 95% CI [0.84–1.60], p  = 0.38). Occurrence of cardiac events was evaluated by logistic regression. Except for patients with serious hypokalemia at admission, the depth of dyskalemia was associated with increased risk of cardiac events. Conclusions Dyskalemia is common at ICU admission and associated with increased mortality. Occurrence of cardiac events increased with dyskalemia depth. A correction of serum potassium level by day 2 was associated with improved prognosis.