Early proximal tubular injury in COVID-19 related ARDS: the URICOV study (preprint)

Background: During COVID-19, renal impairment is the most frequent after lung impairment and is associated with a poor prognosis particularly in intensive care unit (ICU). In this work we aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and to compare them with patients with non-COVID-19-related ARDS. Methods: This prospective multicenter study was conducted in 3 ICUs. Patients aged 18 years and older with invasive mechanical ventilation for ARDS were enrolled. Precise evaluation of renal dysfunction markers including urinary proteins electrophoresis (UPE) and quantification, was performed within 24 hours after mechanical ventilation onset. Results: From March 2020 to December 2021, 135 patients in ICU for ARDS were enrolled: 100 COVID-19 ARDS and 35 non-COVID-19 ARDS. UPE found more tubular dysfunction in COVID-19 patients (68% vs. 21.4%, p<0.0001) and more normal profiles in non-COVID-19 patients (65.0% vs. 11.2%, p=0.0003). COVID-19 patients significantly displayed early urinary leakage of tubular proteins like beta-2-microglobulin and free-light chains, tended to display more frequently acute kidney injury (AKI) (51.0% vs 34.3%, p=0.088), and had longer mechanical ventilation (20 vs. 9 days, p<0.0001) and longer ICU length of stay (26 vs. 15 days, p<0.0001). In COVID-19 ARDS, leakage of free lambda light chain was significantly associated with the onset of KDIGO ≥2 AKI (OR: 1.014, 95%CI [1.003-1.025], p=0.011). Conclusion: Patients admitted to the ICU for COVID-19-related ARDS display a proximal tubular dysfunction, prior to the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable and non-invasive tool to assess proximal tubular dysfunction in the ICU. Trial Registration: Registered retrospectively with www.clinicaltrials.gov (NCT05699889) 26 January 2023.

Effects of a chair positioning session in awake non-intubated COVID-19 pneumonia patients: a multicenter, observational, pilot study using lung ultrasound (preprint)

BackgroundLung ultrasound (LUS) is a validated tool for the management of coronavirus disease 2019 (COVID-19)-related pneumonia. An awake prone positioning (PP) improves oxygenation and outcomes in COVID-19 non-intubated patients, but its tolerance remains an issue. A chair positioning (CP) may have beneficial effects on oxygenation and lung aeration. Thus, CP could be an easier alternative to PP. This study assessed the effects of a CP session on oxygenation (using SpO2:FiO2 ratio) and lung aeration (using lung reaeration score) changes in non-intubated COVID-19 patients. Methods An observational multicenter study was conducted in three university hospital intensive care units (ICUs). We retrospectively analyzed prospectively collected data from LUS exams performed before and after a CP session in non-intubated COVID-19 patients. Patients were divided into groups of responders or non-responders in terms of oxygenation and lung aeration.ResultsOf the 33 patients included in the study, 14 (44%) were oxygenation non-responders and 18 (56%) were oxygenation responders, and 13 (40.6%) and 19 (59.4%) patients were classified as lung aeration non-responders and responders, respectively. Changes in oxygenation and lung aeration before and after a CP session were not correlated (Pearson’s r = -0.19, p = 0.3, 95% CI: -0.5–0.17). The reaeration scores did not differ between oxygenation responders and non-responders (1 [-0.75–3.75] vs. 4, [-1–6], p = 0.41). The LUS score was significantly correlated with SpO2:FiO2 ratio before a CP session (Pearson’s r = 0.37, p = 0.04, 95% CI: 0.03–0.64) but not after (Pearson’s r = 0.17, p = 0.35, 95% CI: -0.19–0.50). Conclusion A CP session was associated with improved oxygenation and lung aeration in more than half of the non-intubated COVID-19 patients. However, oxygenation and lung aeration changes were not associated, suggesting that a CP session induces a ventilation:perfusion matching alteration.

Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically Ill Patients with COVID-19 (preprint)

Background: Kidney failure is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe acute kidney injury (AKI) in critically ill COVID-19 patients.MethodsIn this cohort study, data from consecutive patients hospitalized in 6 ICUs for COVID-19 were retrospectively collected. The incidence and severity of AKI were monitored during the entire ICU stay. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included.Results164 patients were included in the final analysis, 97 (59.1%) displayed AKI, of which 39 (23.8%) severe stage 3 AKI and 21 (12.8%) requiring renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with Angiotensin Converting Enzyme inhibitors (ACEI) exposure (p=0.016), arterial hypertension (p=0.029), APACHE-II score (p=0.004) and mortality at D28 (p=0.008), D60 (p<0.001) and D90 (p<0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307-13.736), p=0.016), APACHE II score (without age) (OR: 1.138 (1.044-1.241), p=0.003) and iNO (OR: 5.694 (1.953-16.606), p=0.001). Protective factors were prone positioning (OR: 0.234 (0.057-0.967), p=0.045) and dexamethasone (OR: 0.194 (0.053-0.713), p=0.014).ConclusionsDexamethasone was associated with a prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19 related ARDS.

Characteristics and outcomes of Acute Respiratory Distress Syndrome related to COVID-19 in Belgian and French Intensive Care Units according to antiviral strategies. The COVADIS multicenter observational study. (preprint)

BackgroundLimited data are available for antiviral therapy efficacy especially for the most severe patients under mechanical ventilation suffering from Covid-19 related Acute Respiratory Distress Syndrome (ARDS). MethodsObservational multicenter cohort of patients with moderate to severe Covid-19 ARDS, comparing antiviral strategies (none, hydroxychloroquine (HCQ), lopinavir/ritonavir (L/R), others (combination or remdesivir). The primary end-point was the day-28 ventilator free days (VFD), patients which died before d28 were considered as having 0 VFD. The variable was dichotomized in patients still ventilated or dead at day 28 vs patients being extubated and alive at day 28 (VFD = or >0). ResultsWe analyzed 376 patients (80 with standard of care (SOC), 49 treated with L/R, 197 with HCQ, and 50 others). The median number of d28-VFD was 0 (IQR 0-13) and was different across the different groups (P=0.01), the SOC patients having the highest d28-VFD. A multivariate logistic regression including antiviral strategies, showed that age (OR 0.95 CI95%:0.93-0.98), male gender (OR 0.53 CI95%:0.31-0.93), Charlson score (OR 0.85 CI95%:0.73-0.99) and plateau pressure (OR 0.94 CI95%:0.88-0.99) were associated with having 0 d28-VFD whereas P/F ratio (OR 1.005 CI95%:1.001-1.010) was associated with having [≥]1 d28-VFD (ie. being extubated and alive). Acute kidney injury (AKI) was frequent (64%), its incidence was different across the patients groups (P=0.01). In a post-hoc logistic multivariate regression apart from demographics characteristics and comorbidities, the use of L/R (administered to 81 of 376 patients was associated with occurrence of AKI (OR 2.07 CI95%:1.17-3.66) and need for renal replacement therapy (RRT). ConclusionIn this observational study of moderate to severe Covid-19 ARDS patients, we did not observed a benefit of treating patients with any specific antiviral treatment. We observed an association between L/R treatment and occurrence of AKI and need for RRT. Take home messageAny specific COVID-19 antiviral treatment is associated with higher ventilator free days at day 28 as compared to no antiviral treatment for patient in ICU under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of acute kidney injury. TweetCOVID-19: Insights from ARDS cohort: no signal of efficacy for antiviral treatments. Lopinavir/ritonavir may be associated with AKI and need for RRT.