Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

NUCLEAR REACTION ANALYSIS OF HYDROGEN SURFACE CONTAMINATION OF Al(Li) ALLOYS

The resonant nuclear reaction 1H(15N, αγ) has been used to non destructively depth-profile hydrogen near the suzface of Al(Li) binary alloys. Lithium is one of the rare interference of this technique but we show how to extract its contribution. In order to reduce or eliminate the hydrogen surface contamination (affecting the bulk content determination) various treatments (machining-annealing) have been investigated

Transpulmonary thermodilution detects rapid and reversible increases in lung water induced by positive end-expiratory pressure in acute respiratory distress syndrome

Purpose: It has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (PEEP) may lead to an artefactual overestimation of extravascular lung water (EVLW) by transpulmonary thermodilution (TPTD). Methods: In 60 ARDS patients, we measured EVLW (PiCCO2 device) at a PEEP level set to reach a plateau pressure of 30&nbsp;cmH2O (HighPEEPstart) and 15 and 45&nbsp;min after decreasing PEEP to 5&nbsp;cmH2O (LowPEEP15′ and LowPEEP45′, respectively). Then, we increased PEEP back to the baseline level (HighPEEPend). Between HighPEEPstart and LowPEEP15′, we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (Crs) in the whole population, or by measuring the lung derecruited volume in 30 patients. We defined patients with a large derecruitment from the other ones as patients in whom the Crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population. Results: Reducing PEEP from HighPEEPstart (14 ± 2&nbsp;cmH2O) to LowPEEP15′ significantly decreased EVLW from 20 ± 4 to 18 ± 4&nbsp;mL/kg, central venous pressure (CVP) from 15 ± 4 to 12 ± 4&nbsp;mmHg, the arterial oxygen tension over inspired oxygen fraction (PaO2/FiO2) ratio from 184 ± 76 to 150 ± 69&nbsp;mmHg and lung volume by 144 [68–420]&nbsp;mL. The EVLW decrease was similar in “large derecruiters” and the other patients. When PEEP was re-increased to HighPEEPend, CVP, PaO2/FiO2 and EVLW significantly re-increased. At linear mixed effect model, EVLW changes were significantly determined only by changes in PEEP and CVP (p &lt; 0.001 and p = 0.03, respectively, n = 60). When the same analysis was performed by estimating recruitment according to lung volume changes (n = 30), CVP remained significantly associated to the changes in EVLW (p &lt; 0.001). Conclusions: In ARDS patients, changing the PEEP level induced parallel, small and reversible changes in EVLW. These changes were not due to an artefact of the TPTD technique and were likely due to the PEEP-induced changes in CVP, which is the backward pressure of the lung lymphatic drainage. Trial registration ID RCB: 2015-A01654-45. Registered 23 October 2015