Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Lung aeration estimated by chest electrical impedance tomography and lung ultrasound during extubation.

BACKGROUND: This study hypothesized that patients with extubation failure exhibit a loss of lung aeration and heterogeneity in air distribution, which could be monitored by chest EIT and lung ultrasound. Patients at risk of extubation failure were included after a successful spontaneous breathing trial. Lung ultrasound [with calculation of lung ultrasound score (LUS)] and chest EIT [with calculation of the global inhomogeneity index, frontback center of ventilation (CoV), regional ventilation delay (RVD) and surface available for ventilation] were performed before extubation during pressure support ventilation (H0) and two hours after extubation during spontaneous breathing (H2). EIT was then repeated 6 h (H6) after extubation. EIT derived indices and LUS were compared between patients successfully extubated and patients with extubation failure. RESULTS: 40 patients were included, of whom 12 (30%) failed extubation. Before extubation, when compared with patients with successful extubation, patients who failed extubation had a higher LUS (19 vs 10, p = 0.003) and a smaller surface available for ventilation (352 vs 406 pixels, p = 0.042). After extubation, GI index and LUS were higher in the extubation failure group, whereas the surface available for ventilation was lower. The RVD and the CoV were not different between groups. CONCLUSION: Before extubation, a loss of lung aeration was observed in patients who developed extubation failure afterwards. After extubation, this loss of lung aeration persisted and was associated with regional lung ventilation heterogeneity. Trial registration Clinical trials, NCT04180410, Registered 27 November 2019-prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04180410 .

Chatbot-based serious games: A useful tool for training medical students? A randomized controlled trial.

OBJECTIVES: Chatbots, conversational agents that walk medical students (MS) though a clinical case, are serious games that seem to be appreciated by MS. Their impact on MS's performance in exams however was not yet evaluated. Chatprogress is a chatbot-based game developed at Paris Descartes University. It contains 8 pulmonology cases with step-by-step answers delivered with pedagogical comments. The CHATPROGRESS study aimed to evaluate the impact of Chatprogress on students' success rate in their end-term exams. METHODS: We conducted a post-test randomized controlled trial held on all fourth-year MS at Paris Descartes University. All MS were asked to follow the University's regular lectures, and half of them were randomly given access to Chatprogress. At the end of the term, medical students were evaluated on pulmonology, cardiology and critical care medicine. MAIN OUTCOMES MEASURES: The primary aim was to evaluate an increase in scores in the pulmonology sub-test for students who had access to Chatprogress, compared to those who didn't. Secondary aims were to evaluate an increase in scores in the overall test (Pulmonology, Cardiology and Critical care medicine test (PCC)) and to evaluate the correlation between access to Chatprogress and overall test score. Finally, students' satisfaction was assessed using a survey. RESULTS: From 10/2018 to 06/2019, 171 students had access to Chatprogress (the Gamers) and among them, 104 ended up using it (the Users). Gamers and Users were compared to 255 Controls with no access to Chatprogress. Differences in scores on the pulmonology sub-test over the academic year were significantly higher among Gamers and Users vs Controls (mean score: 12.7/20 vs 12.0/20, p = 0.0104 and mean score: 12.7/20 vs 12.0/20, p = 0.0365 respectively). This significant difference was present as well in the overall PCC test scores: (mean score: 12.5/20 vs 12.1/20, p = 0.0285 and 12.6/20 vs 12.1/20, p = 0.0355 respectively). Although no significant correlation was found between the pulmonology sub-test's scores and MS's assiduity parameters (number of finished games among the 8 proposed to Users and number of times a User finished a game), there was a trend to a better correlation when users were evaluated on a subject covered by Chatprogress. MS were also found to be fans of this teaching tool, asking for more pedagogical comments even when they got the questions right. CONCLUSION: This randomised controlled trial is the first to demonstrate a significant improvement in students' results (in both the pulmonology subtest and the overall PCC exam) when they had access to Chatbots, and even more so when they actually used it.

Insulin therapy and blood glucose management in critically ill patients: a 1-day cross-sectional observational study in 69 French intensive care units.

BACKGROUND: Hyperglycaemia is common in critically ill patients, but blood glucose and insulin management may differ widely among intensive care units (ICUs). We aimed to describe insulin use practices and the resulting glycaemic control in French ICUs. We conducted a multicentre 1-day observational study on November 23, 2021, in 69 French ICUs. Adult patients hospitalized for an acute organ failure, severe infection or post-operative care were included. Data were recorded from midnight to 11:59 p.m. the day of the study by 4-h periods. RESULTS: Two ICUs declared to have no insulin protocol. There was a wide disparity in blood glucose targets between ICUs with 35 different target ranges recorded. In 893 included patients we collected 4823 blood glucose values whose distribution varied significantly across ICUs (P < 0.0001). We observed 1135 hyperglycaemias (> 1.8 g/L) in 402 (45.0%) patients, 35 hypoglycaemias (≤ 0.7 g/L) in 26 (2.9%) patients, and one instance of severe hypoglycaemia (≤ 0.4 g/L). Four hundred eight (45.7%) patients received either IV insulin (255 [62.5%]), subcutaneous (SC) insulin (126 [30.9%]), or both (27 [6.6%]). Among patients under protocolized intravenous (IV) insulin, 767/1681 (45.6%) of glycaemias were above the target range. Among patients receiving insulin, short- and long-acting SC insulin use were associated with higher counts of hyperglycaemias as assessed by multivariable negative binomial regression adjusted for the propensity to receive SC insulin: incidence rate ratio of 3.45 (95% confidence interval [CI] 2.97-4.00) (P < 0.0001) and 3.58 (95% CI 2.84-4.52) (P < 0.0001), respectively. CONCLUSIONS: Practices regarding blood glucose management varied widely among French ICUs. Administration of short or long-acting SC insulin was not unusual and associated with more frequent hyperglycaemia. The protocolized insulin algorithms used failed to prevent hyperglycaemic events.

ICU strain and outcome in COVID-19 patients-A multicenter retrospective observational study.

PURPOSE: To compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality. METHODS: In a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality. RESULTS: 640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 --0.31] vs. 1.18 [-0.34-1.29] SD when compared to mean COVID-19 admission in each center during study period, P<0.001). Patients admitted during the second wave were older, had more profound hypoxemia and lower SOFA. High flow nasal cannula was more frequently used during the second wave (68% vs. 39%, P<0.001) and intubation was less frequent (46% vs. 69%, P<0.001). Neither 28-day mortality (30% vs. 26%, P = 0.12) nor hospital mortality (37% vs. 31%, P = 0.27) differed between first and second wave. Overweight and obesity were associated with lower 28-day mortality while older age, underlying chronic kidney disease, severity at ICU admission as assessed by SOFA score and ICU strain were associated with higher 28-day mortality. ICU strain was not associated with hospital mortality. CONCLUSION: The characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.

Curative anticoagulation prevents endothelial lesion in COVID-19 patients.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. OBJECTIVES: To explore the coagulopathy and endothelial dysfunction in COVID-19 patients. METHODS: The study analyzed clinical and biological profiles of patients with suspected COVID-19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). RESULTS: Among 96 consecutive COVID-19-suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS-CoV-2. COVID-19-positive patients were more likely to present with fever (P = .02), cough (P = .03), and pneumonia at computed tomography (CT) scan (P = .002) at admission. Prevalence of D-dimer >500 ng/mL was higher in COVID-19-positive patients (74.2% versus 43.3%; P = .007). No sign of disseminated intravascular coagulation were identified. Adding D-dimers >500 ng/mL to gender and pneumonia at CT scan in receiver operating characteristic curve analysis significantly increased area under the curve for COVID-19 diagnosis. COVID-19-positive patients had significantly more CECs at admission (P = .008) than COVID-19-negative ones. COVID-19-positive patients treated with curative anticoagulant prior to admission had fewer CECs (P = .02) than those without. Interestingly, patients treated with curative anticoagulation and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers had even fewer CECs (P = .007). CONCLUSION: Curative anticoagulation could prevent COVID-19-associated coagulopathy and endothelial lesion.