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.

How automated measurement of lung lesions can predict the course of patients hospitalized with SARS-Cov-2 pneumonia (preprint)

IntroductionThe aim of this study was to evaluate if an automated measurement of lung lesions, epicardial fat and pericardial volume during the days surrounding hospital admission for COVID-19 pneumonia may predict intubation or mortality. The second purpose of this study was to assess whether the association of these Computed Tomography (CT) measures with the SOFA (Sequential Organ Failure Assessment) score, could predict intubation and mortality better than the SOFA score alone.MethodsThis observational retrospective study was conducted in Timone university hospital in Marseille in France, between March 10th and May 10th 2020. All adult patients with COVID-19, admitted with respiratory symptoms and having performed a chest CT three days before to two days after admission were eligible for inclusion. All chest CTs were analyzed using a local automated CT measurement software. The primary outcome was invasive mechanical ventilation (IMV) or death during the 60-day follow-up. Wilcoxon-Mann-Whitney test was used for univariate analysis and logistic regression were calculated for multivariate analysis. Results176 patients were included in the study. 57 (32.4%) received IMV or died during the 60-day follow-up. After univariate analysis, all lung automated volumetric measures of ground-glass (p=0.015), consolidation (p<0.001) and all lesions to parenchymal volume ratio (p<0.001) were significantly higher for the patients who required IMV or who died. All pulmonary-lesion rate was tested in multivariate analysis and remained significantly higher in the IMV or death group (p=0.003), with an Odd Ratio of 3.52 (1.55-8.01, 95% CI) for patients who had more than 19.5% of pulmonary lesion. Pericardial volume and epicardial fat were not significantly associated with IMV or mortality. In this study, the association of the criterion “pulmonary lesion >20%” to the SOFA score improves its predictive value on IMV or mortality with a AUC of 0.82.ConclusionAutomated chest CT measures of COVID-19 patients with respiratory symptoms admitted to hospital showed a significantly higher rate of lung lesions (ground glass, consolidation, or both) for those who later died or required IMV. Furthermore, the association of these automated CT measures to the SOFA score could help select patients requiring ICU upon entering hospital. 

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.

Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19 (preprint)

Background: Daily management to shield chronic dialysis patients from SARS-CoV-2 contamination makes patient care cumbersome. There are no screening methods to date and a molecular biology platform is essential to perform RT-PCR for SARS-CoV-2; however, accessibility remains poor. Our goal was to assess whether the tools routinely used to monitor our hemodialysis patients could represent reliable and quickly accessible diagnostic indicators to improve the management of our hemodialysis patients in this pandemic environment.Methods: In this prospective observational diagnostic study, we recruited patients from La Conception hospital. Patients were eligible for inclusion if suspected of SARS-CoV-2 infection when arriving at our center for a dialysis session between March 12th and April 24th 2020. They were included if both RT-PCR result for SARS-CoV-2 and cell blood count on the day that infection was suspected were available. We calculated the area under the curve (AUC) of the receiver operating characteristic curve.Results: 37 patients were included in the final analysis, of which 16 (43.2%) were COVID-19 positive. For the day of suspected COVID-19, total leukocytes were significantly lower in the COVID-19 positive group (4.1 vs 7.4 G/L, p=0.0072) and were characterized by lower neutrophils (2.7 vs 5.1 G/L, p=0.021) and eosinophils (0.01 vs 0.15 G/L, p=0.0003). Eosinophil count below 0.045 G/L identified SARS-CoV-2 infection with AUC of 0.9 [95% CI 0.81-1] (p<0.0001), sensitivity of 82%, specificity of 86%, a positive predictive value of 82%, a negative predictive value of 86% and a likelihood ratio of 6.04.Conclusions :Eosinophil count enables rapid routine screening of chronic hemodialysis patients suspected of being COVID-19 within a range of low or high probability.