Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges

A Systematic Review of the High-flow Nasal Cannula for Adult Patients

Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Vasopressor and inotrope treatment for septic shock: An umbrella review of reviews

Purpose: To review the characteristics, findings and quality of systematic reviews (SRs) on the effect of any vasopressor/inotrope on outcomes in adult patients with sepsis compared with either no treatment, another vasopressor or inotrope or fluids. Materials and methods: We systematically searched Cochrane Central Register of Controlled Trials, PubMed and Embase (January 1993–March 2021). Descriptive statistics were used. Results: Among the 28 SRs identified, mortality was the primary outcome in most (26/28) and mortality was usually (23/28) studied using randomised controlled trials (RCTs). Fifteen SRs focused exclusively on patients with sepsis or septic shock. Sepsis and septic shock were always grouped for the analysis. Publication bias was consistently low when studied. The most consistent findings were a survival advantage with norepinephrine versus dopamine, which disappeared in analyses restricted to 28-day mortality, and more arrhythmias with dopamine. However, these analyses were dominated by a single study. Only 2 SRs were judged to be of moderate-high quality. Lack of blinding and attrition bias may have affected the outcomes. Conclusions: The quality of SRs on the effect of vasopressors/inotropes on the outcomes of adult patients with sepsis can be improved, but high-quality, multicenter, RCTs should be preferred to additional SRs on this topic

Experimental and Compassionate Drug Use During the First Wave of the COVID-19 Pandemic: A Retrospective Single-Center Study

International audienc

Predictors of Hypoxemia and Related Adverse Outcomes in Patients Hospitalized with COVID-19: A Double-Center Retrospective Study

Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine predictors of hypoxemia and related adverse outcomes among patients hospitalized with COVID-19 in the two largest hospitals in Jerusalem, Israel, from 9 March through 16 July 2020. Patients were categorized as those who developed reduced (<94%) vs. preserved (≥94%) arterial oxygen saturation (SpO2) within the first 48 h after arrival to the emergency department. Overall, 492 hospitalized patients with COVID-19 were retrospectively analyzed. Patients with reduced SpO2 were significantly older, had more comorbidities, higher body surface area (BSA) and body mass index (BMI), lower lymphocyte counts, impaired renal function, and elevated liver enzymes, c-reactive protein (CRP), and D-dimer levels as compared to those with preserved SpO2. In the multivariable regression analysis, older age (odds ratio (OR) 1.02 per year, p < 0.001), higher BSA (OR 1.16 per 0.10 m2, p = 0.003) or BMI (OR 1.05 per 1 kg/m2, p = 0.011), lower lymphocyte counts (OR 1.72 per 1 × 103/μL decrease, p = 0.002), and elevated CRP (1.11 per 1 mg/dL increase, p < 0.001) were found to be independent predictors of low SpO2. Severe hypoxemia requiring ventilatory support, older age, and pre-existing comorbidities, including underlying renal dysfunction and heart failure, were found to be significantly associated with in-hospital mortality. These findings suggest that assessment of predictors of hypoxemia early at the time of hospitalization with COVID-19 may be helpful in risk stratification and management

Moderate Certainty Evidence Suggests the Use of High-Flow Nasal Cannula Does Not Decrease Hypoxia When Compared With Conventional Oxygen Therapy in the Peri-Intubation Period

International audienceObjective: The role of high-flow nasal cannula during and before intubation is unclear despite a number of randomized clinical trials. Our objective was to conduct a systematic review and meta-analysis examining the benefits of high-flow nasal cannula in the peri-intubation period.Data Sources: We performed a comprehensive search of relevant databases (MEDLINE, EMBASE, and Web of Science).Study Selection: We included randomized clinical trials that compared high-flow nasal cannula to other noninvasive oxygen delivery systems in the peri-intubation period.Data Extraction: Our primary outcome was severe desaturation (defined as peripheral oxygen saturation reading < 80% during intubation). Secondary outcomes included peri-intubation complications, apneic time, Pao2 before and after intubation, Paco2 after intubation, ICU length of stay, and short-term mortality.Data Synthesis: We included 10 randomized clinical trials (n = 1,017 patients). High-flow nasal cannula had no effect on the occurrence rate of peri-intubation hypoxemia (relative risk, 0.98; 95% CI, 0.68–1.42; 0.3% absolute risk reduction, moderate certainty), serious complications (relative risk, 0.87; 95% CI, 0.71–1.06), apneic time (mean difference, 10.3 s higher with high-flow nasal cannula; 95% CI, 11.0 s lower to 31.7 s higher), Pao2 measured after preoxygenation (mean difference, 3.6 mm Hg higher; 95% CI, 3.5 mm Hg lower to 10.7 mm Hg higher), or Pao2 measured after intubation (mean difference, 27.0 mm Hg higher; 95% CI, 13.2 mm Hg lower to 67.2 mm Hg higher), when compared with conventional oxygen therapy. There was also no effect on postintubation Paco2, ICU length of stay, or 28-day mortality.Conclusions: We found moderate-to-low certainty evidence that the use of high-flow nasal cannula likely has no effect on severe desaturation, serious complications, apneic time, oxygenation, ICU length of stay, or overall survival when used in the peri-intubation period when compared with conventional oxygen therapy

High flow nasal cannula in the immediate post-operative period: a systematic review and meta-analysis

International audienceBackground: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear.Research Question: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively?Study Design and Methods: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework.Results: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS.Interpretation: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surger