Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

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/)

Traitement chirurgical de l' aspergillose pulmonaire invasive

L aspergillose pulmonaire invasive (API) est une complication infectieuse fréquente et grave de l immunodépression, avec un taux de mortalité de 20 à 80% selon les populations de patients. Le voriconazole est devenu le traitement médical de référence depuis sa mise sur le marché. La chirurgie, considérée comme un traitement potentiellement curatif dans les années 90, a été peu étudiée depuis l apparition de ce nouvel antifongique. Trente patients opérés entre 1990 et 2010 pour une suspicion d aspergillose pulmonaire invasive ont été étudiés de façon globale et en 2 sous-groupes : le groupe A ayant été traité principalement par l amphotéricine B, et le groupe B ayant reçu du voriconazole. Vingt-neuf patients présentaient une pathologie hématologique, et 1 une infection par le VIH. Le diagnostic d API était certain ou probable pour 60% d entre eux. Les indications principales de la chirurgie étaient l élimination d une masse fongique résiduelle avant la poursuite des traitements immunosuppresseurs (50%), le contrôle insatisfaisant de l infection (43%), et le risque d hémoptysie (10%). La mortalité péri-opératoire était faible (3%), et le taux de rechute de 17%. L infection aspergillaire a été confirmée chez 85% des patients du groupe A, et 20% des patients du groupe B (p<0.001). Un autre diagnostic a été découvert pour 40% des patients du groupe B (p=0.008), dont 2 infections à Mucorales. La chirurgie semble être un traitement efficace et relativement bien toléré de l aspergillose pulmonaire invasive. Avec le voriconazole, la proportion de lésions contenant des filaments d Aspergillus semble diminuer, alors que d autres infections sont mises en évidence.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Update on ventilator-associated pneumonia [version 1; referees: 2 approved]

Ventilator-associated pneumonia (VAP) is the most frequent life-threatening nosocomial infection in intensive care units. The diagnostic is difficult because radiological and clinical signs are inaccurate and could be associated with various respiratory diseases. The concept of infection-related ventilator-associated complication has been proposed as a surrogate of VAP to be used as a benchmark indicator of quality of care. Indeed, bundles of prevention measures are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory secretions must be collected for bacteriological secretions before any new antimicrobials. Quantitative distal bacteriological exams may be preferable for a more reliable diagnosis and therefore a more appropriate use antimicrobials. To improve the prognosis, the treatment should be adequate as soon as possible but should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic selection pressure. For empiric treatments, the selection of antimicrobials should consider the local prevalence of microorganisms along with their associated susceptibility profiles. Critically ill patients require high dosages of antimicrobials and more specifically continuous or prolonged infusions for beta-lactams. After patient stabilization, antimicrobials should be maintained for 7–8 days. The evaluation of VAP treatment based on 28-day mortality is being challenged by regulatory agencies, which are working on alternative surrogate endpoints and on trial design optimization

Kyste hydatique pulmonaire autochtone

International audienc

Transplantation pulmonaire : complications per et post-opératoires précoces

La transplantation pulmonaire, traitement de référence des insuffi sances respiratoires terminales, connaît un essorimportant depuis quelques années. Les suites postopératoires dépendent de l’indication de la transplantation pulmonaire,du type de procédure, de la phase peropératoire et de la survenue de complications précoces. Ces complications, chezces patients immunodéprimés, sont dominées par la défaillance primaire du greffon, liée aux phénomènes d’isché-mie–reperfusion, les complications infectieuses essentiellement bactériennes pulmonaires et le rejet aigu cellulaireet/ou humoral. La mortalité précoce est encore de 10 % dans le premier mois. Une prise en charge multidisciplinaireest indispensable pour gérer au mieux cette phase per et postopératoire précoce. </jats:p

Impact of natural light exposure on delirium burden in adult patients receiving invasive mechanical ventilation in the ICU: a prospective study

Abstract Objective To determine whether potential exposure to natural light via windows is associated with reduced delirium burden in critically ill patients admitted to the ICU in a single room. Design Prospective single-center study. Setting Medical ICU of a university hospital, Paris, France. Patients Adult patients receiving invasive mechanical ventilation. Methods Consecutive patients admitted to a single room with (LIGHT group) or without (DARK group) exposure to natural light via windows were evaluated for delirium. The primary endpoint was the incidence of delirium. Main secondary endpoints included incidence of severe agitation intervened with antipsychotics and incidence of hallucinations. Results A total of 195 patients were included (LIGHT group: n = 110; DARK group: n = 85). The incidence of delirium was similar in the LIGHT group and the DARK group (64% vs. 71%; relative risk (RR) 0.89, 95% CI 0.73–1.09). Compared with the DARK group, patients from the LIGHT group were less likely to be intervened with antipsychotics for agitation episodes (13% vs. 25%; RR 0.52, 95% CI 0.27–0.98) and had less frequent hallucinations (11% vs. 22%; RR 0.49, 95% CI 0.24–0.98). In multivariate logistic regression analysis, natural light exposure was independently associated with a reduced risk of agitation episodes intervened with antipsychotics (adjusted odds ratio = 0.39; 95% CI 0.17–0.88). Conclusion Admission to a single room with potential exposure to natural light via windows was not associated with reduced delirium burden, as compared to admission to a single room without windows. However, natural light exposure was associated with a reduced risk of agitation episodes and hallucinations. </jats:sec

Pleural effusion during weaning from mechanical ventilation: a prospective observational multicenter study

Abstract Background Pleural effusion is common during invasive mechanical ventilation, but its role during weaning is unclear. We aimed at assessing the prevalence and risk factors for pleural effusion at initiation of weaning. We also assessed its impact on weaning outcomes and its evolution in patients with difficult weaning. Methods We performed a prospective multicenter study in five intensive care units in France. Two hundred and forty-nine patients were explored using ultrasonography. Presence of moderate-to-large pleural effusion (defined as a maximal interpleural distance ≥ 15 mm) was assessed at weaning start and during difficult weaning. Results Seventy-three (29%) patients failed weaning, including 46 (18%) who failed the first spontaneous breathing trial (SBT) and 39 (16%) who failed extubation. Moderate-to-large pleural effusion was detected in 81 (33%) patients at weaning start. Moderate-to-large pleural effusion was associated with more failures of the first SBT [27 (33%) vs. 19 (11%), p < 0.001], more weaning failures [37 (47%) vs. 36 (22%), p < 0.001], less ventilator-free days at day 28 [21 (5–24) vs. 23 (16–26), p = 0.01], and a higher mortality at day 28 [14 (17%) vs. 14 (8%), p = 0.04]. The association of pleural effusion with weaning failure persisted in multivariable analysis and sensitivity analyses. Short-term (48 h) fluid balance change was not associated with the evolution of interpleural distance in patients with difficult weaning. Conclusions In this multicenter observational study, pleural effusion was frequent during the weaning process and was associated with worse weaning outcomes