Pneumococcal pneumonia and endotoxemia: An experimental and clinical reappraisal.

BACKGROUND: Circulating endotoxins could result from bacterial digestive translocation during sepsis, thus contributing to uncontrolled systemic inflammation, leading in turn to organ dysfunction. We addressed this issue in the setting of severe pneumococcal pneumonia. METHODS: Endotoxemia was measured in a clinically relevant rabbit model of ventilated pneumococcal pneumonia and in 110 patients with bacteraemic pneumonia, using a patented mass spectrometry (LC-MS/MS) method for detection of 3-OH fatty acids (C10, C12, C14, C16 and C18), which are molecules bound to the lipid A motif of LPS. RESULTS: Whereas higher levels of systemic inflammation and organ dysfunctions were found, there was no significant difference in lipopolysaccharide concentrations when infected rabbits were compared to non-infected ones, or when patients were compared to healthy volunteers. CONCLUSIONS: Seemingly, endotoxins do not drive the overwhelming inflammation associated with severe forms of pneumococcal pneumonia.

Ventilatory Management of Patients with Acute Respiratory Distress Syndrome Due to SARS-CoV-2.

The emergence of the new SARS-CoV-2 in December 2019 caused a worldwide pandemic of the resultant disease, COVID-19. There was a massive surge in admissions to intensive care units (ICU), notably of patients with hypoxaemic acute respiratory failure. In these patients, optimal oxygen therapy was crucial. In this article, we discuss tracheal intubation to provide mechanical ventilation in patients with hypoxaemic acute respiratory failure due to SARS-CoV-2. We first describe the pathophysiology of respiratory anomalies leading to acute respiratory distress syndrome (ARDS) due to infection with SARS-CoV-2, and then briefly review management, focusing particularly on the ventilation strategy. Overall, the ventilatory management of ARDS due to SARS-CoV-2 infection is largely the same as that applied in ARDS from other causes, and lung-protective ventilation is recommended. The difference lies in the initial clinical presentation, with profound hypoxaemia often observed concomitantly with near-normal pulmonary compliance.

Role of the interstitium during septic shock: a key to the understanding of fluid dynamics?

BACKGROUND: While not traditionally included in the conceptual understanding of circulation, the interstitium plays a critical role in maintaining fluid homeostasis. Fluid balance regulation is a critical aspect of septic shock, with a well-known association between fluid balance and outcome. The regulation of transcapillary flow is the first key to understand fluid homeostasis during sepsis. MAIN TEXT: Capillary permeability is increased during sepsis, and was classically considered to be necessary and sufficient to explain the increase of capillary filtration during inflammation. However, on the other side of the endothelial wall, the interstitium may play an even greater role to drive capillary leak. Indeed, the interstitial extracellular matrix forms a complex gel-like structure embedded in a collagen skeleton, and has the ability to directly attract intravascular fluid by decreasing its hydrostatic pressure. Thus, interstitium is not a mere passive reservoir, as was long thought, but is probably major determinant of fluid balance regulation during sepsis. Up to this date though, the role of the interstitium during sepsis and septic shock has been largely overlooked. A comprehensive vision of the interstitium may enlight our understanding of septic shock pathophysiology. Overall, we have identified five potential intersections between septic shock pathophysiology and the interstitium: 1. increase of oedema formation, interacting with organ function and metabolites diffusion; 2. interstitial pressure regulation, increasing transcapillary flow; 3. alteration of the extracellular matrix; 4. interstitial secretion of inflammatory mediators; 5. decrease of lymphatic outflow. CONCLUSIONS: We aimed at reviewing the literature and summarizing the current knowledge along these specific axes, as well as methodological aspects related to interstitium exploration.

ICU stays that are judged to be non-beneficial: A qualitative study of the perception of nursing staff.

INTRODUCTION: Non-beneficial stays in the intensive care unit (ICU) may have repercussions for patients and their families, but can also cause suffering among the nursing staff. We aimed explore the perceptions of nursing staff in the ICU about patient stays that are deemed to be "non-beneficial" for the patient, to identify areas amenable to intervention, with a view to improving how the nursing staff perceive the patient pathway before, during and after intensive care. METHODS: Multicentre, qualitative study using individual, semi-structured interviews. All qualified nurses and nurses' aides who were full-time employees in the ICU of three participating centres were invited to participate. Interviews were recorded, transcribed and analyzed using textual content analysis. RESULTS: A total of 21 interviews were performed from February 2020 to October 2021, at which point saturation was reached in the data. Average age of participants was 38.5±7.5 years, and they had an average of 10.7±7.4 years of experience working in the ICU. Four major themes emerged from the interviews, namely: (1) the work is oriented towards life-threatening emergencies, technical procedures and burdensome care; (2) a range of specific criteria and circumstances influence the decisions to admit patients to ICU; (3) there are significant organisational, physical and psychological repercussions associated with a non-beneficial stay in the ICU; (4) respondents made some proposals for improvements to the patient care pathway. CONCLUSION: Nursing staff have a similar perception to physicians regarding admission decisions and non-beneficial ICU stays. The possibility of future ICU admission needs to be anticipated, discussed systematically with patients and integrated into healthcare goals that are consistent with the patient's wishes and preferences, in multi-professional collaboration including nursing and medical staff.

Management of renal replacement therapy among adults in French intensive care units: A bedside practice evaluation.

Background: This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs). Methods: From July 1 to October 5 2021, 67 French ICUs provided data regarding their ICU and RRT implementation. We used an online questionnaire to record general data about each participating ICU, including the type of hospital, number of beds, staff ratios, and RRT implementation. Each center then prospectively recorded RRT parameters from 5 consecutive acute kidney injury (AKI) patients, namely the indication, type of dialysis catheter used, type of catheter lock used, type of RRT (continuous or intermittent), the RRT parameters initially prescribed (dose, blood flow, and duration), and the anticoagulant agent used for the circuit. Results: A total of 303 patients from 67 ICUs were analyzed. Main indications for RRT were oligo-anuria (57.4%), metabolic acidosis (52.1%), and increased plasma urea levels (47.9%). The commonest insertion site was the right internal jugular (45.2%). In 71.0% of cases, the dialysis catheter was inserted by a resident. Ultrasound guidance was used in 97.0% and isovolumic connection in 90.1%. Citrate, unfractionated heparin, and saline were used as catheter locks in 46.9%, 24.1%, and 21.1% of cases, respectively. Conclusions: Practices in French ICUs are largely compliant with current national guidelines and international literature. The findings should be interpreted in light of the limitations inherent to this type of study.

The accuracy of intensive care nurses' interpretation of chest radiographs to recognise misplacement of endotracheal and nasogastric tubes after a single training session and comparison with residents' interpretation.

BACKGROUND: Misplacements of endotracheal and nasogastric tubes are frequent encounters in critically ill patients. OBJECTIVES: The purpose of this study was to assess the effectiveness of a single standardised training session on the ability of intensive care registered nurses (RNs) to recognise the misplacement of endotracheal and nasogastric tubes on bedside chest radiographs of patients in intensive care units (ICUs). METHODS: In eight French ICUs, RNs received a 110-min standardised teaching on the position of endotracheal and nasogastric tubes on chest radiographs. Their knowledge was evaluated within the subsequent weeks. For 20 chest radiographs, each with an endotracheal and nasogastric tube, RNs had to indicate whether each tube was in the proper or incorrect position. Training success was defined as >90% for the lower bound of the 95% confidence interval (95% CI) of the mean correct response rate (CRR). Residents of the participating ICUs underwent the same evaluation (without prior specific training). RESULTS: In total, 181 RNs were trained and evaluated and 110 residents were evaluated. The global mean CRR for RNs was 84.6% (95% CI: 83.3-85.9), significantly higher than for residents (81.4% [95% CI: 79.7-83.2]) (P < 0.0001). The mean CRR for RNs and residents was 95.9% (93.9-98.0) and 97.0% (94.7-99.3) for misplaced nasogastric tubes (P = 0.54), 86.8% (85.2-88.5) and 82.6% (79.4-85.7) (P = 0.07) for nasogastric tubes in the correct position, 86.6% (83.8-89.3) and 62.7% (57.9-67.5) for misplaced endotracheal tubes (P < 0.0001), and 79.1% (76.6-81.6) and 84.7% (82.1-87.2) for endotracheal tubes in the correct position (P = 0.01), respectively. CONCLUSIONS: The ability of trained RNs to detect tube misplacement did not reach the predetermined arbitrary level, indicating training success. Their mean CRR was higher than that for residents and was considered satisfactory for detecting misplaced nasogastric tubes. This finding is encouraging but insufficient to ensure patient safety. Transferring responsibility for reading radiographs to detect the misplacement of endotracheal tubes to intensive care RNs will need a more advanced or more in-depth teaching method.

Non-beneficial admission to the intensive care unit: A nationwide survey of practices.

INTRODUCTION: In a nationwide survey of practices, we sought to define the criteria, circumstances and consequences of non-beneficial admissions to the intensive care unit (ICU), with a view to proposing measures to avoid such situations. METHODS: ICU physicians from a French research in ethics network participated in an online survey. The first part recorded age, sex, and years' experience of the participants. In the second part, there were 8 to 12 proposals on each of 4 main domains: (1) What criteria could be used to qualify an ICU stay as non-beneficial? (2) What circumstances result in the admission of a patient whose ICU stay may later be deemed non-beneficial? (3) What are the consequences of a non-beneficial stay in the ICU? (4) What measures could be implemented to avoid admissions that later come to be considered as non-beneficial? Responses were on a 5-point Likert scale ranging from "Strongly disagree" to "Strongly agree". RESULTS: Among 164 physicians contacted, 154 (94%) responded. The majority cited several criteria used to qualify a stay as non-beneficial. Similarly, >80% cited several possible circumstances that could result in non-beneficial admissions, including lack of knowledge of the case and the patient's history, and failure to anticipate acute deterioration. Possible consequences of non-beneficial stays included stress and anxiety for the patient/family, misunderstandings and conflict. Discussing the utility of possible ICU admission in the framework of the patient's overall healthcare goals was hailed as a means to prevent non-beneficial admissions. CONCLUSION: The results of this survey suggest that joint discussions should take place during the patient's healthcare trajectory, before the acute need for ICU arises, with a view to limiting or avoiding ICU stays that may later come to be deemed "non-beneficial".

Systematic review of locking solutions for non-tunneled hemodialysis catheters.

BACKGROUND: We conducted a systematic review of studies investigating lock solutions for use in non-tunneled hemodialysis catheters. METHODS: We searched PubMed and Cochrane databases from inception to June 11, 2021. Study inclusion criteria were: randomized trial or observational study, adults (>18 years), with acute kidney injury (AKI); and temporary non-tunneled catheters. We recorded bleeding events, catheter dysfunction and complications. RESULTS: Of 649 studies identified, 6 were included (4 randomized, 1 non-randomized trial, 1 retrospective cohort study; sample sizes 78-1496 patients). Citrate was compared to heparin in 4 studies, to saline in 1, and ethanol versus saline in 1. Event-free survival of non-tunneled catheters did not differ between groups. Catheter-related infections and adverse events were less frequent with citrate locks, but reached statistical significance in only two studies. CONCLUSION: Existing data are too heterogeneous to enable recommending one type of catheter lock over any other for non-tunneled hemodialysis catheters.

Endotracheal tube biofilm in critically ill patients during the COVID-19 pandemic : description of an underestimated microbiological compartment.

Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient's environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021.

Anticipating need for intensive care in the healthcare trajectory of patients with chronic disease: A qualitative study among specialists.

INTRODUCTION: We investigated the reflections and perceptions of non-ICU physicians about anticipating the need for ICU admission in case of acute decompensation in patients with chronic disease. METHODS: We performed a qualitative multicentre study using semi-structured interviews among non-ICU specialist physicians. The interview guide, developed in advance, focused on 3 questions: (1) What is your perception of ICU care? (2) How do you think advance directives can be integrated into the patient's healthcare goals? and (3) How can the possibility of a need for ICU admission be integrated into the patient's healthcare goals? Interviews were recorded, transcribed and analysed by thematic analysis. Interviews were performed until theoretical saturation was reached. RESULTS: In total, 16 physicians (8 women, 8 men) were interviewed. The main themes related to intensive care being viewed as a distinct specialty, dispensing very technical care, and with major human and ethical challenges, especially regarding end-of-life issues. The participants also mentioned the difficulty in anticipating an acute decompensation, and the choices that might have to be made in such situations. The timing of discussions about potential decompensation of the patient, the medical culture and the presence of advance directives are issues that arise when attempting to anticipate the question of ICU admission in the patient's healthcare goals or wishes. CONCLUSION: This study describes the perceptions that physicians treating patients with chronic disease have of intensive care, notably that it is a distinct and technical specialty that presents challenging medical and ethical situations. Our study also opens perspectives for actions that could promote a pluridisciplinary approach to anticipating acute decompensation and ICU requirements in patients with chronic disease.

Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response.

Introduction: While QuantiFERON-TB gold (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known. Methods: Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative [interferon (IFN)-γ ≤ 0.5 IU/ml, official threshold] or weak (0.5-2 IU/ml) mitogen response, and one group of controls with normal (>2 IU/ml) mitogen response. Results: A total of 872 patients were included. An ongoing infection was independently associated with both a negative (RR = 4.34; 95% CI = 2.94-6.41) and a weak mitogen response (RR = 2.44; 95% CI = 1.66-3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (3-13), 11 (5-21) and 15 (10-30) days; p < 0.001] and increasing hospital mortality (3, 7, and 15%; p < 0.001). Conclusion: Clinicians should take notice of the mitogen response since IFN-γ concentrations lower than <2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.

A general mathematical model for the in vitro assembly dynamics of intermediate filament proteins.

Intermediate filament (IF) proteins assemble into highly flexible filaments that organize into complex cytoplasmic networks: keratins in all types of epithelia, vimentin in endothelia, and desmin in muscle. Since IF elongation proceeds via end-to-end annealing of unit-length filaments and successively of progressively growing filaments, it is important to know how their remarkable flexibility, i.e., their persistence length lp, influences the assembly kinetics. In fact, their lp ranges between 0.3 µm (keratin K8/K18) and 1.0 µm (vimentin and desmin), and thus is orders of magnitude lower than that of microtubules and F-actin. Here, we present a unique mathematical model, which implements the semiflexible nature of the three IF types based on published semiflexible polymers theories and depends on a single free parameter k0. Calibrating this model to filament mean length dynamics of the three proteins, we demonstrate that the persistence length is indeed essential to accurately describe their assembly kinetics. Furthermore, we reveal that the difference in flexibility alone does not explain the significantly faster assembly rate of keratin filaments compared with that of vimentin. Likewise, desmin assembles approximately six times faster than vimentin, even though both their filaments exhibit the same lp value. These data strongly indicate that differences in their individual amino acid sequences significantly impact the assembly rates. Nevertheless, using a single k0 value for each of these three key representatives of the IF protein family, our advanced model does accurately describe the length distribution and mean length dynamics and provides effective filament assembly rates. It thus provides a tool for future investigations on the impact of posttranslational modifications or amino acid changes of IF proteins on assembly kinetics. This is an important issue, as the discovery of mutations in IF genes causing severe human disease, particularly for desmin and keratins, is steadily increasing.

Adverse Mechanical Ventilation and Pneumococcal Pneumonia Induce Immune and Mitochondrial Dysfunctions Mitigated by Mesenchymal Stem Cells in Rabbits.

BACKGROUND: Mechanical ventilation for pneumonia may contribute to lung injury due to factors that include mitochondrial dysfunction, and mesenchymal stem cells may attenuate injury. This study hypothesized that mechanical ventilation induces immune and mitochondrial dysfunction, with or without pneumococcal pneumonia, that could be mitigated by mesenchymal stem cells alone or combined with antibiotics. METHODS: Male rabbits underwent protective mechanical ventilation (8 ml/kg tidal volume, 5 cm H2O end-expiratory pressure) or adverse mechanical ventilation (20 ml/kg tidal-volume, zero end-expiratory pressure) or were allowed to breathe spontaneously. The same settings were then repeated during pneumococcal pneumonia. Finally, infected animals during adverse mechanical ventilation received human umbilical cord-derived mesenchymal stem cells (3 × 106/kg, intravenous) and/or ceftaroline (20 mg/kg, intramuscular) or sodium chloride, 4 h after pneumococcal challenge. Twenty-four-hour survival (primary outcome), lung injury, bacterial burden, immune and mitochondrial dysfunction, and lung transcriptomes (secondary outcomes) were assessed. RESULTS: High-pressure adverse mechanical ventilation reduced the survival of infected animals (0%; 0 of 7) compared with spontaneous breathing (100%; 7 of 7) and protective mechanical ventilation (86%; 6 of 7; both P < 0.001), with higher lung pathology scores (median [interquartile ranges], 5.5 [4.5 to 7.0] vs. 12.6 [12.0 to 14.0]; P = 0.046), interleukin-8 lung concentrations (106 [54 to 316] vs. 804 [753 to 868] pg/g of lung; P = 0.012), and alveolar mitochondrial DNA release (0.33 [0.28 to 0.36] vs. 0.98 [0.76 to 1.21] ng/µl; P < 0.001) compared with infected spontaneously breathing animals. Survival (0%; 0 of 7; control group) was improved by mesenchymal stem cells (57%; 4 of 7; P = 0.001) or ceftaroline alone (57%; 4 of 7; P < 0.001) and improved even more with a combination treatment (86%; 6 of 7; P < 0.001). Mesenchymal stem cells reduced lung pathology score (8.5 [7.0 to 10.5] vs. 12.6 [12.0 to 14.0]; P = 0.043) and alveolar mitochondrial DNA release (0.39 (0.34 to 0.65) vs. 0.98 (0.76 to 1.21) ng/µl; P = 0.025). Mesenchymal stem cells combined with ceftaroline reduced interleukin-8 lung concentrations (665 [595 to 795] vs. 804 [753 to 868] pg/g of lung; P = 0.007) compared to ceftaroline alone. CONCLUSIONS: In this preclinical study, mesenchymal stem cells improved the outcome of rabbits with pneumonia and high-pressure mechanical ventilation by correcting immune and mitochondrial dysfunction and when combined with the antibiotic ceftaroline was synergistic in mitigating lung inflammation.

Criteria deemed important by ICU patients when designating a reference person.

Background: We investigated the criteria that hospitalized patients in intensive care units (ICUs) deem important when designating relatives who are best qualified to interact with the caregiving staff. Methods: We conducted an exploratory, observational, prospective, multicenter study between March 1, 2018, and October 31, 2018, within two ICUs. A 12-item questionnaire was distributed to patients in the ICUs by the investigating physicians. Patients were considered eligible if they had a good understanding of the French language and if they had not officially designated surrogates before ICU admission. Results: Seventy-one patients whose average age was 63.9± 17.3 years, of whom 21 (29.5%) were females, completed the questionnaire. The average Charlson comorbidity score was 2.5 ± 2.4, and the average Simplified Acute Physiology Score (SAPS II) was 39.8 ± 16.5. The main etiology was respiratory infection (40.8%), followed by sepsis (23.9%). The most important criteria identified by patients when selecting reference persons were a good knowledge of the patient's wishes and values, an emotional attachment to the patient, and being a family member. Conclusion: Our findings reveal that ICU patients considered the following criteria to be critical when designating reference persons: knowledge of their wishes and the existence of emotional and family attachments.

New Methodologies to Study DNA Repair Processes in Space and Time Within Living Cells.

DNA repair requires a coordinated effort from an array of factors that play different roles in the DNA damage response from recognizing and signaling the presence of a break, creating a repair competent environment, and physically repairing the lesion. Due to the rapid nature of many of these events, live-cell microscopy has become an invaluable method to study this process. In this review we outline commonly used tools to induce DNA damage under the microscope and discuss spatio-temporal analysis tools that can bring added information regarding protein dynamics at sites of damage. In particular, we show how to go beyond the classical analysis of protein recruitment curves to be able to assess the dynamic association of the repair factors with the DNA lesions as well as the target-search strategies used to efficiently find these lesions. Finally, we discuss how the use of mathematical models, combined with experimental evidence, can be used to better interpret the complex dynamics of repair proteins at DNA lesions.

Non-readmission decisions in the intensive care unit: A qualitative study of physicians' experience in a multicentre French study.

PURPOSE: Deciding not to re-admit a patient to the intensive care unit (ICU) poses an ethical dilemma for ICU physicians. We aimed to describe and understand the attitudes and perceptions of ICU physicians regarding non-readmission of patients to the ICU. MATERIALS AND METHODS: Multicenter, qualitative study using semi-directed interviews between January and May 2019. All medical staff working full-time in the ICU of five participating centres (two academic and three general, non-academic hospitals) were invited to participate. Participants were asked to describe how they experienced non-readmission decisions in the ICU, and to expand on the manner in which the decision was made, but also on the traceability and timing of the decision. Interviews were recorded, transcribed and analyzed using textual content analysis. RESULTS: In total, 22 physicians participated. Interviews lasted on average 26±7 minutes. There were 14 men and 8 women, average age was 35±9 years, and average length of ICU experience was 7±5 years. The majority of respondents said that they regretted that the question of non-readmission was not addressed before the initial ICU admission. They acknowledged that the ICU stay did lead to more thorough contemplation of the overall goals of care. Multidisciplinary team meetings could help to anticipate the question of readmission within the patient's care pathway. Participants reported that there is a culture of collegial decision-making in the ICU, although the involvement of patients, families and other healthcare professionals in this process is not systematic. The timing and traceability of non-readmission decisions are heterogeneous. CONCLUSIONS: Non-readmission decisions are a major issue that raises ethical questions surrounding the fact that there is no discussion of the patient's goals of care in advance. Better anticipation, and better communication with the patients, families and other healthcare providers are suggested as areas that could be targeted for improvement.

CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). METHODS: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. RESULTS: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1ß concentrations. CONCLUSION: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03955887.