The Effect of Positive Pressure Ventilation on Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: An Observational Study.

INTRODUCTION: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS. METHODS: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected. RESULTS: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively. CONCLUSIONS: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function.

Extended criteria liver donation after circulatory death with prolonged warm ischemia: a pilot experience of normothermic regional perfusion and no subsequent ex-situ machine perfusion.

BACKGROUND: Livers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. METHODS: Prospectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. RESULTS: The median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. CONCLUSIONS: This pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the "classic ARDS", showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. METHODS: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. RESULTS: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32-47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. CONCLUSIONS: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

Coagulopathy and COVID-19.

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called 'COVID-19 associated coagulopathy' (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined.

A 57-year-old man with rapidly progressive pulmonary hypertension.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a rare condition associated with neoplastic disorders, predominantly gastric cancer, leading to pre-capillary Pulmonary Hypertension (PH). The pathologic mechanism involved is a fibrocellular intimal proliferation of small pulmonary vessels sustained by nests of carcinomatous cells lodged in pulmonary vasculature. Clinical presentation is nonspecific, including progressive dyspnea and dry cough. Diagnosis of PTTM is extremely challenging ante-mortem and prognosis is poor. Here we describe the case of a middle-aged man, without known previous cancer history. The clinical course was rapidly unfavorable, with progressive dyspnea and PH associated with hemodynamic instability, eventually culminating in patient's death. PTTM diagnosis was made post-mortem. PTTM should be considered in any patient presenting with unexplained PH, especially if it is rapidly progressive, poorly responsive to standard approaches or there is suspected history of malignancy. A prompt diagnosis of PTTM could help in bringing light into this still under-recognized condition.

Biomarkers of Inflammation and Lung Recovery in Extracorporeal Membrane Oxygenation Patients With Persistent Pulmonary Hypertension of the Newborn: A Feasibility Study.

OBJECTIVES: Extracorporeal membrane oxygenation is a treatment for Persistent Pulmonary Hypertension of the Newborn with high mortality. HYPOTHESIS: the extracorporeal membrane oxygenation circuit results in inflammatory responses that mitigate against successful weaning. DESIGN: Single-center prospective observational feasibility study. SETTING: PICU. PATIENTS: Twenty-four neonates requiring extracorporeal membrane oxygenation support for Persistent Pulmonary Hypertension of the Newborn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The reference outcome was death or more than 7 days of extracorporeal membrane oxygenation support. Other outcomes included serial measures of plasma-free hemoglobin and markers of its metabolism, leucocyte, platelet and endothelial activation, and biomarkers of inflammation. Of 24 participants recruited between February 2016 and June 2017, 10 died or required prolonged extracorporeal membrane oxygenation support. These patients were sicker at baseline with higher levels of plasma-free hemoglobin within 12 hours of cannulation (geometric mean ratio, 1.92; 95% CIs, 1.00-3.67; p = 0.050) but not thereafter, versus those requiring less than 7 days extracorporeal membrane oxygenation. Serum haptoglobin concentrations were significantly elevated in both groups. Patients who died or required prolonged extracorporeal membrane oxygenation support demonstrated elevated levels of platelet-leucocyte aggregation, but decreased concentrations of mediators of the inflammatory response: interleukin-8, C-reactive protein, and tumor necrosis factor α. CONCLUSIONS: Clinical status at baseline and not levels of plasma-free hemoglobin or the systemic inflammatory response may determine the requirement for prolonged extracorporeal membrane oxygenation support in neonates.

The ELSO Maastricht Treaty for ECLS Nomenclature: abbreviations for cannulation configuration in extracorporeal life support - a position paper of the Extracorporeal Life Support Organization.

BACKGROUND: The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. METHODS: We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. RESULTS: The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. CONCLUSIONS: A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.

The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A Position Paper of the Extracorporeal Life Support Organization.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.

Leadless Pacemaker Implantation, Focusing on Patients With Conduction System Disorders Post-Transcatheter Aortic Valve Replacement: A Retrospective Analysis.

Background: Impairment of the conduction system is a common complication of transcatheter aortic valve replacement (TAVR), which is typically performed in elderly patients. A leadless pacemaker (LP) may be a suitable option in this frail population, but the available scientific data concerning the efficacy and safety of leadless pacing after TAVR are sparse. The purpose of this analysis was to evaluate the efficacy and safety of LP implantation in patients with relevant bradycardias after TAVR, compared to other indications. Methods: Consecutive patients were retrospectively enrolled. Demographics, background heart diseases, interventional parameters, and follow-up data were collected. Results: A total of 257 consecutive patients who underwent LP implantation were included. In 26 patients, the device was implanted due to bradycardias after TAVR (TAVR group), whereas the remaining 231 patients were in the population without previous TAVR (non-TAVR group). The mean implantation duration (56 ± 22 minutes in the TAVR group vs 48 ± 20 minutes in the non-TAVR group; P = not significant [NS]) and the implantation success rate (100% in the TAVR group vs 98.7% in the non-TAVR group; P = NS) were similar in the 2 cohorts. No significant differences occurred in pacing parameters (sensing, impedance, and threshold, respectively) between the 2 groups, either at implantation or during follow-up. A total of 8 major periprocedural complications (3.1% of patients in total; 3.8% in the TAVR group vs 3.0% in the non-TAVR group; P = NS) occurred within 30 days, without significant difference between the 2 groups. Conclusions: LP implantation appears to be safe and effective in patients after TAVR, and therefore, this procedure is a suitable option for this often old and frail population.

Contexte: L'atteinte du système de conduction cardiaque est une complication courante du remplacement valvulaire aortique par cathéter (RVAC), une intervention habituellement pratiquée chez les patients âgés. Un stimulateur cardiaque sans sonde peut être une option convenable pour cette population fragile, mais les données scientifiques actuelles concernant l'efficacité et l'innocuité de la stimulation sans sonde après un RVAC sont fragmentaires. Cette analyse visait à évaluer l'efficacité et l'innocuité de l'implantation d'un stimulateur cardiaque sans sonde chez des patients atteints de bradycardies pertinentes après un RVAC, comparativement à d'autres indications. Méthodologie: Des patients consécutifs ont été recrutés de manière rétrospective. Les données démographiques, les maladies cardiaques sous-jacentes, les paramètres interventionnels et les données de suivi ont été colligés. Résultats: Un total de 257 patients consécutifs qui se sont fait implanter un stimulateur cardiaque sans sonde ont été inclus. Chez 26 patients, le dispositif a été implanté en raison d'une bradycardie après un RVAC (groupe RVAC), alors que les 231 autres patients formaient la population sans RVAC antérieur (groupe sans RVAC). La durée moyenne de l'intervention d'implantation (56 ± 22 minutes dans le groupe RVAC vs 48 ± 20 minutes dans le groupe sans RVAC; p = non significatif [NS]) et le taux de réussite de l'implantation (100 % dans le groupe RVAC vs 98,7 % dans le groupe sans RVAC; p = NS) étaient similaires dans les deux cohortes. Aucune différence significative n'a été observée dans les paramètres de stimulation (sensibilité, impédance et seuil, respectivement) entre les 2 groupes, que ce soit au moment de l'implantation ou pendant le suivi. Un total de 8 complications périopératoires majeures (3,1 % de l'ensemble des patients; 3,8 % dans le groupe RVAC vs 3,0 % dans le groupe sans RVAC; p = NS) sont survenues dans les 30 jours, sans différence notable entre les 2 groupes. Conclusions: L'implantation d'un stimulateur cardiaque sans sonde semble sûre et efficace après un RVAC; par conséquent, cette intervention représente une option convenable pour cette population souvent âgée et fragile.

Living Donor Lung Transplantation After Hematopoietic Stem Cell Transplantation From the Same Donor: A Risk Worth Taking.

Living donor (LD) lung transplantation (LT) represents an exceptional procedure in Western countries. However, in selected situations, it could be a source of unique advantages, besides addressing organ shortage. We report a successful case of father-to-child single-lobe LT, because of the complications of hematopoietic stem cell transplantation from the same donor, with initial low-dose immunosuppressive therapy and subsequent early discontinuation. Full donor chimerism was hypothesized to be a mechanism of transplant tolerance, and this postulated immunological benefit was deemed to outweigh the risks of living donation and the possible drawbacks of single compared with bilateral LT. Favorable size matching and donor's anatomy, accurate surgical planning, and specific expertise in pediatric transplantation also contributed to the optimal recipient and donor outcomes. Ten months after LD LT, the patient's steadily good lung function after withdrawal of immunosuppressive therapy seems to confirm the original hypothesis.

Leadless Pacemaker Implantation in Patients With a Prior Conventional Pacing System.

Background: Leadless pacing has been established as an alternative approach to transvenous devices for selected patients. Often, leadless pacemaker (LP) implantation is a de novo procedure, but in an increasing number of patients, an LP is used after previous implantation of a conventional pacing system (CPS). Methods: A retrospective analysis was conducted of the efficacy and safety of LP implantation in the context of a previously implanted CPS, from 2 large Swiss centres. Results: A total of 257 consecutive patients undergoing LP implantation were included. They were divided into 2 groups: group 1 consisted of 233 patients who did not have a previous CPS, and group 2 consisted of 24 patients with an in situ CPS. In group 2, a total of 20 patients (83%) required transvenous lead extraction due to infection, malfunction, or other reasons. In 3 patients with device-related infection, lead extraction and LP implantation was performed as a single procedure, whereas in the remaining 11 cases, a time window occurred between the 2 procedures (median: 11.5 days; range: 2-186 days). Electrical device parameters at implantation and during follow-up did not differ between the 2 groups (mean: 12.5 ± 9.3 months). Eight major periprocedural complications (3.1%) were encountered (4 pericardial effusions, 3 instances of femoral bleeding, and 1 instance of intra-abdominal bleeding) in the entire cohort within a 30-day period. No complications occurred in the group with a previous device. No infections were registered, even when complete extraction of an infected CPS was performed prior to LP implantation. Conclusions: Implantation of an LP in patients with a prior CPS (with or without extraction of the previous system) was effective and safe in our population of patients.

Contexte: La stimulation cardiaque sans fil a été établie comme une solution de substitution aux dispositifs transveineux chez certains patients. L'implantation d'un stimulateur cardiaque sans fil est souvent une intervention de novo, mais chez un nombre croissant de patients, ce type de stimulateur est utilisé après l'implantation d'un stimulateur classique. Méthodologie: Une analyse rétrospective de l'efficacité et de l'innocuité de la stimulation cardiaque sans fil dans le contexte de l'implantation d'un stimulateur classique a été réalisée dans deux grands centres suisses. Résultats: Un total de 257 patients consécutifs ayant subi l'implantation d'un stimulateur cardiaque sans fil ont été inclus. Les patients étaient répartis dans deux groupes; le groupe 1 était composé de 233 patients non porteurs d'un stimulateur classique, et le groupe 2, de 24 patients porteurs d'un stimulateur classique in situ. Dans le groupe 2, 20 patients au total (83 %) ont eu besoin d'une extraction de la sonde transveineuse en raison d'une infection, d'un défaut de fonctionnement, ou pour d'autres motifs. Chez 3 patients présentant une infection liée au stimulateur, l'extraction de la sonde et l'implantation d'un stimulateur cardiaque sans fil ont été réalisées simultanément, tandis que dans les 11 autres cas, il s'est écoulé un temps médian de 11,5 jours entre les deux interventions (min.-max. : 2-186 jours). Les paramètres relatifs au dispositif électrique au moment de l'implantation et pendant le suivi n'étaient pas différents entre les deux groupes (moyenne : 12,5 ± 9,3 mois). Huit complications périopératoires importantes (3,1 %) sont survenues (4 cas d'épanchement péricardique, 3 cas d'hémorragie fémorale et 1 cas d'hémorragie intra-abdominale) dans l'ensemble de la cohorte au cours d'une période de 30 jours. Aucune complication ne s'est produite dans le groupe de patients porteurs d'un stimulateur classique. On n'a enregistré aucun cas d'infection, même lorsque l'extraction complète du stimulateur classique infecté a été effectuée avant l'implantation du stimulateur cardiaque sans fil. Conclusions: L'implantation d'un stimulateur cardiaque sans fil chez les patients porteurs d'un stimulateur classique (avec ou sans extraction de ce stimulateur) était une intervention efficace et sûre dans cette population de patients.

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study.

The performance of viscoelastic coagulation monitor (VCM) compared with TEG 5000 (TEG) is unknown. In this multicenter study, the authors evaluated the agreement among VCM/TEG parameters and their relationship with standard coagulation tests in critically ill patients. Viscoelastic coagulation monitor, TEG, and laboratory samples were analyzed simultaneously. Viscoelastic coagulation monitor/TEG agreement was computed by Bland and Altman's plots, association with laboratory parameters was studied with Spearman's correlation coefficient and random-intercept linear models. One-hundred and twenty-seven patients enrolled, 320 paired observations: 210 (65.6%) under unfractioned heparin (UFH), 94 (29.4%) under low molecular weight heparin (LMWH), 16 (5.0%) no heparin. Under UFH prolonged clot formation times and reduced the amplitude of viscoelastic tracings on both devices, especially on TEG. The type of heparin affected the agreement between VCM/TEG homolog parameters. Reaction time (TEG-R) resulted 23.1 min longer than the homolog clotting time (VCM-CT) under UFH; maximum amplitude (TEG-MA) resulted 29.5 mm higher than maximum clot firmness (VCM-MCF) under LMWH. Weak correlation was observed between VCM-CT/TEG-R and activated partial thromboplastin time (aPTT)/anti-Xa; no correlation was found between VCM-alpha/TEG-angle and fibrinogen concentration. Viscoelastic coagulation monitor-MCF showed strong (LWMH) to moderate (UFH) correlation with platelet count, while TEG-MA only showed lower correlation. Viscoelastic coagulation monitor and TEG are differently affected by heparin. The platelet count is well represented by VCM-MCF even during UFH administration.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Worsening of gas exchange parameters at high FiO2 in COVID-19: misleading or informative?

BACKGROUND: In COVID-19, higher than expected level of intrapulmonary shunt has been described, in association with a discrepancy between the initial relatively preserved lung mechanics and the hypoxia severity. This study aim was to measure the shunt fraction and variations of PaO2/FiO2 ratio and oxygen alveolar-arterial gradient (A-a O2) at different FiO2. METHODS: Shunt was measured by a non-invasive system during spontaneous breathing in 12 patients hospitalized at COVID-19 Semi-Intensive Care Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, between October 22 and November 23, 2020. RESULTS: Nine patients were men, mean age (±SD) 62±15 years, mean BMI 27.5±4.8 Kg/m2. Systemic hypertension, diabetes type 2 and previous myocardial infarction were referred in 33%, 17%, and 7%, respectively. Mean PaO2/FiO2 ratio was 234±66 and 11 patients presented a bilateral chest X-ray involvement. Mean shunt was 21±6%. Mainly in patients with a more severe respiratory failure, we found a progressive decrease of PaO2/FiO2 ratio with higher FiO2. Considering (A-a O2), we found a uniform tendency to increase with FiO2 increasing. Even in this case, the more severe were the patients, the higher was the slope, suggesting FiO2 insensitiveness due to a shunt effect, as strengthened by our measurements. CONCLUSION: Relying on a single evaluation of PaO2/FiO2 ratio, especially at high FiO2, could be misleading in COVID-19. We propose a two steps evaluation, the first at low SpO2 value (e.g., 92-94%) and the second one at high FiO2 (i.e., >0.7), allowing to characterize both the amendable (ventilation/perfusion mismatch), and the fixed (shunt) contribution quote of respiratory impairment, respectively.

Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection.

BACKGROUND: Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents. METHODS: We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-α levels were measured by ELISA. FINDINGS: Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-α serum levels. INTERPRETATION: In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity. FUNDING: Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.

Successful Treatment of Pregnant and Postpartum Women With Severe COVID-19 Associated Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation.

There are limited data on the use of extracorporeal membrane oxygenation (ECMO) for pregnant and peripartum women with COVID-19 associated acute respiratory distress syndrome (ARDS). Pregnant women may exhibit more severe infections with COVID-19, requiring intensive care. We supported nine pregnant or peripartum women with COVID-19 ARDS with ECMO, all surviving and suffering no major complications from ECMO. Our case series demonstrates high-maternal survival rates with ECMO support in the management of COVID-19 associated severe ARDS, highlighting that these pregnant and postpartum patients should be supported with ECMO during this pandemic.

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.