The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Health related quality of life, physical function, and cognitive performance in mechanically ventilated COVID-19 patients: A long term follow-up study.

BACKGROUND: Survivors of severe COVID-19 related respiratory failure may experience durable functional impairments. We aimed at investigating health-related quality of life (HR-QoL), physical functioning, fatigue, and cognitive outcomes in COVID-19 patients who received invasive mechanical ventilation (IMV). METHODS: Case-series, prospective, observational cohort study at 18 months from hospital discharge. Patients referring to the Intensive Care Unit (ICU) of Humanitas Research Hospital (Milan, Italy) were recruited if they needed IMV due to COVID-19 related respiratory failure. After 18 months, these patients underwent the 6-min walking test (6MWT), the Italian version of the 5-level EQ-5D questionnaire (EQ-5D-5L), the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire (FACIT-F), the Trail Making Test-B (TMT-B) and the Montreal Cognitive Assessment-BLIND test (MoCA-BLIND). RESULTS: 105 patients were studied. The population's age was 60 ± 10 years on average, with a median Frailty Scale of 2 (Hodgson et al., 2017; Carenzo et al., 2021a [2,3]). EQ-VAS was 80 [70-90] out of 100, walked distance was 406 [331-465] meters, corresponding to about 74 ± 19,1% of the predicted value. FACIT-F score was 43 [36-49] out of 52, and MoCa-BLIND score was 19 (DeSalvo et al., 2006; von Elm et al., 2008; Herdman et al., 2011; Scalone et al., 2015 [16-20]) out of 22. The median TMT-B time was 90 [62-120] seconds. We found a possible age and gender specific effect on HR-QoL and fatigue. CONCLUSIONS: After 18 months from ICU discharge, survivors of severe COVID-19 respiratory failure experience a moderate reduction in HR-QoL, and a severe reduction in physical functioning. Fatigue prevalence is higher in younger patients and in females. Finally, cognitive impairment was present at a low frequency.

Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study.

OBJECTIVES: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient's respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN: Retrospective observational cohort study. SETTING: Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION: The transition period from CMV to PSV was evaluated. We defined it as "failure of assisted breathing" if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99-1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42-3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS: Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Estimation of normal lung weight index in healthy female domestic pigs.

INTRODUCTION: Lung weight is an important study endpoint to assess lung edema in porcine experiments on acute respiratory distress syndrome and ventilatory induced lung injury. Evidence on the relationship between lung-body weight relationship is lacking in the literature. The aim of this work is to provide a reference equation between normal lung and body weight in female domestic piglets. MATERIALS AND METHODS: 177 healthy female domestic piglets from previous studies were included in the analysis. Lung weight was assessed either via a CT-scan before any experimental injury or with a scale after autopsy. The animals were randomly divided in a training (n = 141) and a validation population (n = 36). The relation between body weight and lung weight index (lung weight/body weight, g/kg) was described by an exponential function on the training population. The equation was tested on the validation population. A Bland-Altman analysis was performed to compare the lung weight index in the validation population and its theoretical value calculated with the reference equation. RESULTS: A good fit was found between the validation population and the exponential equation extracted from the training population (RMSE = 0.060). The equation to determine lung weight index from body weight was: [Formula: see text] At the Bland and Altman analyses, the mean bias between the real and the expected lung weight index was - 0.26 g/kg (95% CI - 0.96-0.43), upper LOA 3.80 g/kg [95% CI 2.59-5.01], lower LOA - 4.33 g/kg [95% CI = - 5.54-(- 3.12)]. CONCLUSIONS: This exponential function might be a valuable tool to assess lung edema in experiments involving 16-50 kg female domestic piglets. The error that can be made due to the 95% confidence intervals of the formula is smaller than the one made considering the lung to body weight as a linear relationship.