Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19.

COVID-19 produces cytokine-mediated persistent inflammation and is associated with elevated iron stores and low circulating iron. It is believed that central to the pathophysiological mechanism is interleukin 6 and hepcidin. A state of iron overload, termed hyperferritinemia, and inflammatory anemia take place. Both conditions are linked to a worse result in critically ill patients. Blocking the interleukin 6-hepcidin pathway with Tocilizumab could present favorable outcomes. The aim of this study was to evaluate if Tocilizumab influences survival, the occurrence of sepsis, anemia and transfusions in critically ill patients suffering from COVID-19. This prospective observational study focused on levels of interleukin 6, hepcidin and blood iron parameters in patients treated with Tocilizumab. Data were compared before and after therapy as well as between treated and control groups. Results indicate that there is no difference in terms of survival nor in the rate of anemia or sepsis occurrence. Hepcidin was elevated and anemia ensued after treatment, which could indicate alternative pathways. In conclusion, when the classic interleukin 6-hepcidin pathway is blocked, inflammation seems to use alternative routes. Further understanding of these pathways is required and new pharmacological therapies need to be developed to treat persistent inflammation.

The Dynamics of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict Progression to Septic Shock and Death in Patients with Prolonged Intensive Care Unit Stay.

Background and objectives: The prognoses of patients experiencing a prolonged stay in the intensive care unit (ICU) are often significantly altered by hospital-acquired infections (HAIs), the early detection of which might be cumbersome. The aim of this study was to investigate the roles of the neutrophil-to-lymphocyte (NLR), derived-NRL (d-NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-C-reactive protein (LCR) ratios in predicting the progression to septic shock and death. Materials and Methods: A retrospective analysis of a consecutive series of ninety COVID-19 patients with prolonged hospitalization (exceeding 15 days) admitted to the ICU was conducted. The prevalence of culture-proven HAIs throughout their hospital stays was documented. NLR, dNLR, PLR, and LCR were recorded on admission, day 7, and day 14 to assess their discriminative prowess for detecting further progression to septic shock or death. Results: The prevalence of HAIs was 76.6%, 50% of patients met the criteria for septic shock, and 50% died. The median time to the first positive culture was 13.5 days and 20.5 days for developing septic shock. Mechanical ventilation was a key contributing factor to HAI, septic shock, and mortality. On admission and day 7 NLR, dNLR, PLR, and LCR values had no prognostic relevance for events occurring late during hospitalization. However, day-14 NLR, dNLR, and PLR were independent predictors for progression to septic shock and mortality and have shown good discriminative capabilities. The AUCs for septic shock were 0.762, 0.764, and 0.716, while the values for predicting in-hospital death were 0.782, 0.778, and 0.758, respectively. Conclusions: NLR, dNLR, and PLR are quick, easy-to-use, cheap, effective biomarkers for the detection of a more severe disease course, of the late development of HAIs, and of the risk of death in critically ill patients requiring a prolonged ICU stay.

Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania: A prospective, cohort, multicentre study of 9000 patients.

BACKGROUND: The epidemiology of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be different worldwide. Despite similarities in medicine quality and formation, there are also significant differences concerning healthcare and ICU organisation, staffing, financial resources and population compliance and adherence. Large cohort data of critically ill patients from Central and Eastern Europe are also lacking. OBJECTIVES: The study objectives were to describe the clinical characteristics of patients admitted to Romanian ICUs with SARS-CoV-2 infection and to identify the factors associated with ICU mortality. DESIGN: Prospective, cohort, observational study. SETTING: National recruitment, multicentre study, between March 2020 to March 2021. PATIENTS: All patients with SARS-CoV-2 infection admitted to Romanian ICUs were eligible. There were no exclusion criteria. INTERVENTION: None. MAIN OUTCOME MEASURE: ICU mortality. RESULTS: The statistical analysis included 9058 patients with definitive ICU outcome. The multivariable mixed effects logistic regression model found that age [odds ratio (OR) 1.27; 95% confidence interval (CI), 1.23 to 1.31], male gender (OR 1.21; 95% CI 1.05 to 1.4), medical history of neoplasia (OR 1.74; 95% CI, 1.36 to 2.22), chronic kidney disease (OR 1.54; 95% CI, 1.27 to 1.88), type II diabetes (OR 1.23; 95% CI, 1.06 to 1.43), chronic heart failure (OR 1.24; 95% CI, 1.03 to 1.49), dyspnoea (OR 1.3; 95% CI, 1.1 to 1.5), SpO2 less than 90% (OR 3; 95% CI, 2.5 to 3.5), admission SOFA score (OR 1.07; 95% CI, 1.05 to 1.09), acute respiratory distress syndrome (ARDS) on ICU admission (OR 1.35; 95% CI, 1.1 to 1.63) and the need for noninvasive (OR 1.8, 95% CI, 1.5 to 1.22) or invasive ventilation (OR 28; 95% CI, 22 to 35) and neuromuscular blockade (OR 3.5; 95% CI, 2.6 to 4.8), were associated with larger ICU mortality.Higher GCS on admission (OR 0.81; 95% CI, 0.79 to 0.83), treatment with hydroxychloroquine (OR 0.78; 95% CI, 0.64 to 0.95) and tocilizumab (OR 0.58; 95% CI, 0.48 to 0.71) were inversely associated with ICU mortality. CONCLUSION: The SARS-CoV-2 critically ill Romanian patients share common personal and clinical characteristics with published European cohorts. Public health measures and vaccination campaign should focus on patients at risk.

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study.

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research.

Nutritional Risk Assessment Scores Effectively Predict Mortality in Critically Ill Patients with Severe COVID-19.

BACKGROUND: Malnutrition predicts a worse outcome for critically ill patients. However, quick, easy-to-use nutritional risk assessment tools have not been adequately validated. AIMS AND METHODS: The study aimed to evaluate the role of four biological nutritional risk assessment instruments (the Prognostic Nutritional Index-PNI, the Controlling Nutritional Status Score-CONUT, the Nutrition Risk in Critically Ill-NUTRIC, and the modified NUTRIC-mNUTRIC), along with CT-derived fat tissue and muscle mass measurements in predicting in-hospital mortality in a consecutive series of 90 patients hospitalized in the intensive care unit for COVID-19-associated ARDS. RESULTS: In-hospital mortality was 46.7% (n = 42/90). Non-survivors had a significantly higher nutritional risk, as expressed by all four scores. All scores were independent predictors of mortality on the multivariate regression models. PNI had the best discriminative capabilities for mortality, with an area under the curve (AUC) of 0.77 for a cut-off value of 28.05. All scores had an AUC above 0.72. The volume of fat tissue and muscle mass were not associated with increased mortality risk. CONCLUSIONS: PNI, CONUT, NUTRIC, and mNUTRIC are valuable nutritional risk assessment tools that can accurately predict mortality in critically ill patients with COVID-19-associated ARDS.

A.B.C. approach proposal for POCUS in COVID-19 critically ill patients.

The rapid spread of SARS-CoV-2 (COVID-19) since December 2019 forced Intensive Care Units to face high numbers of patients admitted simultaneously with limited resources. COVID-19 critically ill patients, especially those on mechanical ventilators, demand special attention as they can develop potential complications with critical hemodynamic and respiratory consequences. Point of Care Ultrasound (POCUS) might have important roles in assessing the critically ill SARS-CoV-2 patient. Mostly, lung ultrasound has been presented as having a role in diagnosis and monitoring, but airway examination and hemodynamic evaluation are of interest also. We propose an A.B.C. POCUS approach focusing on A-airway (orotracheal intubation), B-breathing (interstitial syn-dromes, pneumothorax, atelectasis, pneumonia), and C-circulation (cardiac function, pulmonary embolism, volume status, deep veins thrombosis). This A.B.C. approach has emerged during ICU care for 22 adult COVID-19 critically ill patients, along with the analysis of recent papers describing ultrasound in COVID-19 patients including the use of ultrasound that is currently applied in the management of the general critically ill population. This A.B.C- POCUS algorithm parallels the well-established clinical A.B.C. algorithms. There are few extensive ultrasonographic studies in COVID-19 critically ill patients up to now, but techniques extrapolated from non-COVID studies seem reasonable even though comparative studies are not available yet.