Epidemiology and Outcome of Early-Onset Acute Kidney Injury and Recovery in Critically Ill COVID-19 Patients: A Retrospective Analysis.

BACKGROUND: The clinical significance of early-onset acute kidney injury (EO-AKI) and recovery in severe COVID-19 intensive care unit (ICU) patients is poorly documented. OBJECTIVE: The aim of the study was to assess the epidemiology and outcome of EO-AKI and recovery in ICU patients admitted for SARS-CoV-2 pneumonia. DESIGN: This was a retrospective single-centre study. SETTING: The study was carried out at the medical ICU of the university hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged ≥18 years admitted between 20 March 2020 and 31 August 2021 for SARS-CoV-2 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and with an ICU length of stay (LOS) ≤72 h were excluded. INTERVENTIONS: EO-AKI was defined on the basis of serum creatinine levels according to the Kidney Disease Improving Global Outcomes criteria, developing ≤7 days. Depending on renal recovery, defined by the normalization of serum creatinine levels, EO-AKI was transient (recovery within 48 h), persistent (recovery between 3 and 7 days) or AKD (no recovery within 7 days after EO-AKI onset). MEASUREMENTS: Uni- and multivariate analyses were performed to determine factors associated with EO-AKI and EO-AKI recovery. MAIN RESULTS: EO-AKI occurred in 84/266 (31.5%) study patients, of whom 42 (50%), 17 (20.2%) and 25 (29.7%) had EO-AKI stages 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 40 (47.6%), 15 (17.8%) and 29 (34.6%) patients, respectively. The 90-day mortality was 87/244 (35.6%) and increased with EO-AKI occurrence and severity: no EO-AKI, 38/168 (22.6%); EO-AKI stage 1, 22/39 (56.4%); stage 2, 9/15 (60%); and stage 3, 18/22 (81.8%) (p < 0.01). The 90-day mortality in patients with transient or persistent AKI and AKD was 20/36 (55.6%), 8/14 (57.1%) and 21/26 (80.8%), respectively (p < 0.01). MAKE-90 occurred in 42.6% of all patients. CONCLUSIONS: In ICU patients admitted for SARS-CoV-2 pneumonia, the development of EO-AKI and time to recovery beyond day 7 of onset were associated with poor outcome.

Severe SARS-Cov2 pneumonia in vaccinated patients: a multicenter cohort study.

Vaccination reduces risk of infection, hospitalization, and death due to SARS-Cov2. Vaccinated patients may however experience severe SARS-Cov2 disease. The objective was to describe clinical features of vaccinated patients requiring intensive care unit (ICU) admission due to SARS-Cov2 infection and compare them to a published cohort of unvaccinated patients. We performed a multicenter cohort study of patients with severe SARS-Cov2 disease admitted to 15 ICUs in France between January and September 2021. 100 consecutive vaccinated patients (68 (68%) men, median age 64 [57-71]) were included. Immunosuppression was reported in 38 (38%) patients. Among available serologies at ICU admission, 64% exhibited an optimal antibody level. Median SOFA score at ICU admission was 4 [4-6.3] and median PaO2/FiO2 ratio was 84 [69-128] mmHg. A total of 79 (79%) and 18 (18%) patients received high flow nasal oxygen and non-invasive mechanical ventilation, respectively. Invasive mechanical ventilation (IMV) was initiated in 48 (48%) with a median duration of 11 [5-19] days. During a median ICU length-of-stay of 8 [4-20] days, 31 (31%) patients died. Age (OR per 5-years increment 1.38 CI95% [1.02-1.85], p = 0.035), and SOFA at ICU admission (OR 1.40 CI95% [1.14-1.72] per point, p = 0.002) were independently associated with mortality. When compared to a cohort of 1316 unvaccinated patients (72% men, median age 63 [53-71]), vaccinated patients exhibited less frequently diabetes (16 [16%] vs. 351 [27%], p = 0.029) but were more frequently immunosuppressed (38 [38%] vs. 109 (8.3%), p < 0.0001), had more frequently chronic kidney disease (24 [24%] vs. 89 (6.8%), p < 0.0001), chronic heart failure (16 [16%] vs. 58 [4.4%], p < 0.0001), and chronic liver disease (3 [3%] vs. 8 [0.6%], p = 0.037) compared to unvaccinated patients. Despite similar severity, vaccinated patients required less frequently IMV at ICU day 1 and during ICU stay (23 [23%] vs. 785 [59.7%], p < 0.0001, and 48 [48%] vs. 930 [70.7%], p < 0.0001, respectively). There was no difference concerning ICU mortality (31 [31%] vs. 379 [28.8%], p = 0.64). Severe SARS-Cov2 infection after vaccination occurs mainly in patients with immunosuppression, chronic kidney, heart or liver failure. Age and disease severity are independently associated with mortality.

Hypercoagulability in critically ill patients with COVID 19, an observational prospective study.

OBJECTIVE: COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. DESIGN: Prospective observational study. SETTING: Monocentric, intensive care, University Hospital of Clermont Ferrand, France. PATIENTS: Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. INTERVENTIONS: Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 µg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. MEASUREMENTS AND MAIN RESULTS: Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. CONCLUSIONS: Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.

Association of nitrogen balance trajectories with clinical outcomes in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND & AIMS: The intensity and duration of the catabolic phase in COVID-19 patients can differ between survivors and non-survivors. The purpose of the study was to assess the determinants of, and association between, nitrogen balance trajectories and outcome in critically ill COVID-19 patients. METHODS: This retrospective monocentric observational study involved patients admitted to the intensive care unit (ICU) of the University Hospital of Clermont Ferrand, France, from January 2020 to May 2021 for COVID-19 pneumonia. Patients were excluded if referred from another ICU, if their ICU length of stay was <72 h, or if they were treated with renal replacement therapy during the first seven days after ICU admission. Data were collected prospectively at admission and during ICU stay. Death was recorded at the end of ICU stay. Comparisons of the time course of nitrogen balance according to outcome were analyzed using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni- and multivariate logistic regression analyses were performed to assess the impact of a non-negative nitrogen-balance on ICU death. To investigate the relationships between nitrogen balance, inflammatory markers and protein intake, linear and non-nonlinear models were run at days 3, 5 and 7, and the amount of protein intake necessary to reach a neutral nitrogen balance was calculated. Subgroup analyses were carried out according to BMI, age, and sex. RESULTS: 99 patients were included. At day 3, a similar negative nitrogen balance was observed in survivors and non-survivors: -16.4 g/d [-26.5, -3.3] and -17.3 g/d [-22.2, -3.8] (p = 0.54). The trajectories of nitrogen balance over time thus differed between survivors and non-survivors (p = 0.01). In survivors, nitrogen balance increased over time, but decreased from day 2 to day 6 in non-survivors, and thereafter increased slowly up to day 14. At days 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen balance. CONCLUSION: We report a prolonged catabolic state in COVID patients that seemed more pronounced in non-survivors than in survivors. Our study underlines the need for monitoring urinary nitrogen excretion to guide the amount of protein intake required by COVID-19 patients.

Severe COVID-19 is characterized by the co-occurrence of moderate cytokine inflammation and severe monocyte dysregulation.

BACKGROUND: SARS-CoV-2 has been responsible for considerable mortality worldwide, owing in particular to pulmonary failures such as ARDS, but also to other visceral failures and secondary infections. Recent progress in the characterization of the immunological mechanisms that result in severe organ injury led to the emergence of two successive hypotheses simultaneously tested here: hyperinflammation with cytokine storm syndrome or dysregulation of protective immunity resulting in immunosuppression and unrestrained viral dissemination. METHODS: In a prospective observational monocentric study of 134 patients, we analysed a panel of plasma inflammatory and anti-inflammatory cytokines and measured monocyte dysregulation via their membrane expression of HLA-DR. We first compared the results of patients with moderate forms hospitalized in an infectious disease unit with those of patients with severe forms hospitalized in an intensive care unit. In the latter group of patients, we then analysed the differences between the surviving and non-surviving groups and between the groups with or without secondary infections. FINDINGS: Higher blood IL-6 levels, lower quantitative expression of HLA-DR on blood monocytes and higher IL-6/mHLA-DR ratios were statistically associated with the risk of severe forms of the disease and among the latter with death and the early onset of secondary infections. INTERPRETATION: The unique immunological profile in patients with severe COVID-19 corresponds to a moderate cytokine inflammation associated with severe monocyte dysregulation. Individuals with major CSS were rare in our cohort of hospitalized patients, especially since the use of corticosteroids, but formed a very severe subgroup of the disease. FUNDING: None.