Predictive factors for secondary intensive care unit admission within 48 hours after hospitalization in a medical ward from the emergency room

International audienceBACKGROUND:Unplanned transfer to an ICU within 48 hours of admission from the emergency department (ED) can be considered an adverse event. Screening at risk for such an event is a challenge for ED staff. Our purpose was to identify the clinical and biological variables which may be identified in the ED setting and can predict short-term unplanned secondary transfer to the intensive care setting.METHODS:This was a three-year retrospective case controlled monocentric study. The cases were patients transferred to a medical ICU within 48 hours of admission to the general wards from the ED. Each case was matched to two controls (patients not transferred to the ICU) based on age, gender, year of admission, and hospital unit. A conditional logistic regression was performed.RESULTS:Three hundred nineteen patients, including 107 cases and 212 controls, were studied. Community-acquired pneumonia (CAP) was the most frequent diagnosis (23% of cases) followed by sepsis (16%). We identified six predictive factors of an unplanned short-term transfer to the ICU. Former smoking status, fever between 38°C and 40°C, dyspnea as the chief complaint in the ED, a lower MEDS score, an elevated acute physiology age chronic health evaluation score, and the ordering of an arterial blood gas each correlate with secondary transfer to an intensive care setting.CONCLUSION:We report a higher risk of short-term unscheduled ICU transfer in patients meeting these criteria. These patients should be closely monitored and frequently re-evaluated before being transferred to a general ward

Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study

International audienceBackgroundEarly sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP).MethodsSubjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP).ResultsA total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78–0.84] and 0.86 [0.84–0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79–0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84–0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83–0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2–7.1, 95% CI] and Sepsis-3 by 7.6 [5.1–11.3, 95% CI].ConclusionsMDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department.Trial Registration ClinicalTrials.gov (NCT03588325)

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old