Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection

IntroductionBronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making.AimTo identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDSMethodsMulticenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance.ResultsAfter adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-α were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1α, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a protein-based prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively.ConclusionBAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BAS-based protein testing emerges as a novel tool for risk assessment in the ICU

Diferencias en los valores de procalcitonina en las bacteriemias por gram positivos y gram negativos en pacientes con sepsis grave y shock séptico

Introduction: Procalcitonin (PCR) is elevated in bacterial infections and discriminates between bacterial infections and of a noninfectious inflammatory response (SIRS). Objective: To determine whether there are differences between the values of PCT for gram negative (GN) and gram positive (GP) in bacteremias secondary to severe sepsis and septic shock and identify their behavior in renal failure (RF). Material and method: Retrospective observational cohort .Bacteremias by GN and GP from 1 January to 31 December 2011. The focus, clinical features, severity scales, hyperlactataemia (lactate ≥ 3 mmol / l) and average, minimum and maximum concentrations of PCT and CRP (PCR) were estudied. PCT clearance at 48 and 72 h. Quantitative variables analyzed by chi-square and t-Student by continuous or non-parametric tests. Results: 106 bacteremia in 97 patients. Main focus: 32 lung (30.2%). Bacteremia: GN 59.4% and 40.6% GP. Major pathogen: 34.9% E Coli. We show no significant differences in SIRS criteria and severity scales. The hyperlactataemia and hypoxemia were more frequent in the GP in GN (38.5% vs 11.9% p = 0.02 and 48.7% vs 27.1% p = 0.03). PCT values in GN bacteremia were higher without statistical significance. There was statistical significance in the mean serum PCT values (p = 0.05) in patients with chronic renal failure. Conclusions: There was not significant differences in determinations of PCT in GN and GP bacteremia. In patients with chronic renal failure PCT concentrations were higher in episodes of bacteremia GN. The hyperlactatemia was more frequent bacteremia GP.Introducción: La procalcitonina (PCT) se eleva en infecciones bacterianas y discrimina entre una infección bacteriana de una respuesta inflamatoria no infecciosa (SIRS). Objetivo: Determinar si existen diferencias entre valores de PCT para gram negativo (GN) y gram positivo (GP) en bacteriemias secundaria a sepsis grave y shock séptico e identificar su comportamiento en insuficiencia renal (IR). Material y método: Estudio de cohortes observacional retrospectivo .Bacteriemias por GN y GP del 1 enero al 31 de diciembre 2011 .Se estudió el foco, características clínicas, escalas de gravedad e hiperlactacidemia (lactato ≥ 3mmol/l). Concentraciones medias, mínimas y máximas de PCT y proteína C reactiva (PCR). El aclaramiento de PCT a 48 y 72 h. Analizamos variables cuantitativas mediante chi-cuadrado y continuas mediante t-Student o pruebas no paramétricas. Resultados: 106 bacteriemias en 97 pacientes. Principal foco: 32 pulmonar (30,2%). Bacteriemias: 59,4% de GN y un 40,6% GP. Principal patógeno: 34,9% E Coli. No evidenciamos diferencias significativas en criterios de SIRS y escalas de gravedad. Hiperlactacidemia e hipoxemia fueron más frecuentes en GP que en GN (38,5% vs 11,9% p=0,02 y 48,7% vs 27,1% p=0,03). Valores de PCT en bacteriemias por GN eran más elevados sin significación estadística. En pacientes con fracaso renal crónico si encontramos significación estadística en valores séricos medios de PCT (p=0,05). Conclusiones: No encontramos diferencias significativas en determinaciones de PCT en bacteriemias por GN y GP. Pacientes con fracaso renal crónico, concentraciones de PCT fueron más elevadas en episodios de bacteriemia por GN. La hiperlactacidemia fue más frecuente en bacteriemias por GP