Drotrecogin alpha (activated) (DAA), or recombinant human activated protein C, is a new treatment in sepsis-induced multiple organ failure, leading to significant reduction in the mortality rate, thanks to its anticoagulant properties. It has been suggested that DAA has anti-inflammatory and antiapoptotic effects in sepsis animal models. This study investigates the potential actions of DAA on circulating mononuclear cells apoptosis in human septic shock. Prospective, cohort study. Two intensive care wards and two research laboratories in a university hospital. Twenty-two septic shock patients with DAA treatment (DAA+), 19 septic shock patients without DAA treatment (DAA-), and 14 healthy controls were successively enrolled, but only 20 DAA+ and 16 DAA- patients fulfilled criteria for statistical analysis. Blood samples were collected at inclusion and 24 hrs later. Circulating mononuclear cell apoptosis levels were assessed by flow cytometry with annexin V, and variations of the apoptotic rheostats (Bax/Bcl-2 and Bax/Bcl-xl ratios) were analyzed by real-time reverse transcription-polymerase chain reaction. Apoptosis was significantly increased in septic shock patients (DAA+, 12 +/- 6.4%; DAA-, 10.4 +/- 5%) vs. healthy patients (3.4 +/- 2.1%, p < .001). Twenty-four hours after DAA infusion, apoptosis was significantly lower in the DAA+ group compared with DAA- ones (respectively, 11.7 +/- 5.3% and 16.2 +/- 7.6%, p < .001). At inclusion, DAA+ and DAA- groups showed comparable Bax/Bcl-2 ratio (DAA+, 0.92 +/- 0.9; DAA-, 1.32 +/- 0.87) and Bax/Bcl-xl ratio (DAA+, 2 +/- 1.04; DAA-, 1.31 +/- 0.93). In contrast, 24 hrs later we observed a significant decrease in these ratios, indicating an antiapoptotic effect in the DAA+ group (Bax/Bcl-2, 0.39 +/- 0.27; Bax/Bcl-xl, 0.68 +/- 0.35) compared with the DAA- group (Bax/Bcl-2, 1.81 +/- 1.1; Bax/Bcl-xl, 1.22 +/- 0.92, p = .001 and p = .039, respectively). In vivo, in human septic shock, DAA has antiapoptotic effects on circulating mononuclear cells, assessed by a significant decrease of both the Bax/Bcl-2 and Bax/Bcl-xl ratios.

(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000–1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024–3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286–4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates the respiratory epithelium through angiotensin-converting enzyme-2 (ACE2) binding. Myocardial and endothelial expression of ACE2 could account for the growing body of reported evidence of myocardial injury in severe forms of Human Coronavirus Disease 2019 (COVID-19). We aimed to provide insight into the impact of troponin (hsTnI) elevation on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with the SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 772 adult, symptomatic COVID-19 patients were hospitalized for more than 24 h in our institution, of whom 375 had a hsTnI measurement and were included in this analysis. The median age was 66 (55–74) years, and there were 67% of men. Overall, 205 (55%) patients were placed under mechanical ventilation and 90 (24%) died. A rise in hsTnI was noted in 34% of the cohort, whereas only three patients had acute coronary syndrome (ACS) and one case of myocarditis. Death occurred more frequently in patients with hsTnI elevation (HR 3.95, 95% CI 2.69–5.71). In the multivariate regression model, a rise in hsTnI was independently associated with mortality (OR 3.12, 95% CI 1.49–6.65) as well as age ≥ 65 years old (OR 3.17, 95% CI 1.45–7.18) and CRP ≥ 100 mg/L (OR 3.62, 95% CI 1.12–13.98). After performing a sensitivity analysis for the missing values of hsTnI, troponin elevation remained independently and significantly associated with death (OR 3.84, 95% CI 1.78–8.28). (4) Conclusion: Our study showed a four-fold increased risk of death in the case of a rise in hsTnI, underlining the prognostic value of troponin assessment in the COVID-19 context.

(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336–0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000–1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996–1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946–7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality.

Introduction: Healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Eosinophils are multifunctional leukocytes implicated in the pathogenesis of several inflammatory processes including viral infections. We focus our study on the prognostic value of eosinopenia as a marker of disease severity and mortality in COVID-19 patients. Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective study on a cohort of COVID-19 patients (moderate or severe disease) who were hospitalized after presenting to the emergency department (ED). We led our study in six major hospitals of northeast France, one of the outbreak’s epicenters in Europe. Results: We have collected data from 1035 patients, with a confirmed diagnosis of COVID-19. More than three quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the intensive care unit (ICU). Mean circulating eosinophils rate, at admission, varied according to disease severity (p < 0.001), yet it did not differ between survivors and non-survivors (p = 0.306). Extreme eosinopenia (=0/mm³) was predictive of severity (aOR = 1.77, p = 0.009); however, it was not predictive of mortality (aOR = 0.892, p = 0.696). The areas under the Receiver operating characteristics (ROC) curve were, respectively, 58.5% (CI95%: 55.3–61.7%) and 51.4% (CI95%: 46.8–56.1%) for the ability of circulating eosinophil rates to predict disease severity and mortality. Conclusion: Eosinopenia is very common and often profound in cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Eosinopenia was not a useful predictor of mortality; however, undetectable eosinophils (=0/mm³) were predictive of disease severity during the initial ED management.