Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092–0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.

Surface EMG-based Quantification of Inspiratory Effort: A Quantitative Comparison with Pes

Background Inspiratory patient effort under assisted mechanical ventilation is an important quantity for assessing patient-ventilator interaction and recognizing over and under assistance. An established clinical standard is respiratory muscle pressure Pmus, derived from esophageal pressure (Pes), which requires the correct placement and calibration of an esophageal balloon catheter. Surface electromyography (sEMG) of the respiratory muscles represents a promising and straightforward alternative technique, enabling non-invasive monitoring of patient activity. Methods A prospective observational study was conducted with patients under assisted mechanical ventilation, who were scheduled for elective bronchoscopy. Airway flow and pressure, esophageal/gastric pressures and sEMG of the diaphragm and intercostal muscles were recorded at four levels of pressure support ventilation. Patient efforts were quantified via the Pmus–time product (PTPmus), the transdiaphragmatic pressure–time product (PTPdi) and the EMG–time products (ETP) of the two sEMG channels. To improve the signal-to-noise ratio, a method for automatically selecting the more informative of the sEMG channels was investigated. Correlation between ETP and PTPmus was assessed by determining a neuromechanical conversion factor KEMG between the two quantities. Moreover, it was investigated whether this scalar can be reliably determined from airway pressure during occlusion maneuvers, thus allowing to quantify inspiratory effort based solely on sEMG measurements. Results In total, 62 patients with heterogeneous pulmonary diseases were enrolled in the study, 43 of wich were included in the data analysis. The ETP of the two sEMG channels was well correlated with PTPmus (r=0.79±0.25 and r=0.84±0.16 for diaphragm and intercostal recordings, respectively). The proposed automatic channel selection method improved correlation with PTPmus (r=0.87±0.09). The neuromechanical conversion factor obtained by fitting ETP to PTPmus varied widely between patients (KEMG=4.32±3.73 cmH2O/μV) and was highly correlated with the scalar determined during occlusions (r=0.95, p<.001). The occlusion-based method for deriving PTPmus from ETP showed a breath-wise deviation to PTPmus of 0.43±1.73 cmH2Os across all datasets. Conclusion These results support the use of surface electromyography as a reliable non-invasive alternative for monitoring breath-by-breath inspiratory effort of patients under assisted mechanical ventilation.

Dynamics of SARS-CoV2 Infection and Multi-Drug Resistant Bacteria Superinfection in Patients With Assisted Mechanical Ventilation

ObjectiveTo investigate the presence of bacteria and fungi in bronchial aspirate (BA) samples from 43 mechanically ventilated patients with severe COVID-19 disease.MethodsDetection of SARS-CoV-2 was performed using Allplex 2019-nCoV assay kits. Isolation and characterisation of bacteria and fungi were carried out in BA specimens treated with 1X dithiothreitol 1% for 30 min at room temperature, using standard culture procedures.ResultsBacterial and/or fungal superinfection was detected in 25 out of 43 mechanically ventilated patients, generally after 7 days of hospitalisation in an intensive care unit (ICU). Microbial colonisation (colony forming units (CFU) &lt;1000 colonies/ml) in BA samples was observed in 11 out of 43 patients, whereas only 7 patients did not show any signs of bacterial or fungal growth. Pseudomonas aeruginosa was identified in 17 patients. Interestingly, 11 out of these 17 isolates also showed carbapenem resistance. The molecular analysis demonstrated that resistance to carbapenems was primarily related to OprD mutation or deletion. Klebsiella pneumoniae was the second most isolated pathogen found in 13 samples, of which 8 were carbapenemase-producer strains.ConclusionThese data demonstrate the detection of bacterial superinfection and antimicrobial resistance in severe SARS-CoV-2-infected patients and suggest that bacteria may play an important role in COVID-19 evolution. A prospective study is needed to verify the incidence of bacterial and fungal infections and their influence on the health outcomes of COVID-19 patients.

POS1233 USE OF BARICITINIB AND TOCILIZUMAB FOR THE TREATMENT OF MODERATE TO SEVERE COVID-19 IN HOSPITALIZED PATIENTS

Background:SARS-CoV2 infection and COVID-19 associated pneumonia are associated to a dysregulated inflammatory response known as cytokine storm and the use of cytokine inhibitors, especially those targeting IL-6, has been proposed as a therapeutic alternative in these patients. Janus Kinase (JAK) inhibitors in combination to the antiviral Remdesivir have shown evidence of reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or noninvasive ventilation1.Objectives:To describe the outcomes associated with the use of Tocilizumab (TCZ) and Baricitinib (Bari) in patients hospitalized for COVID-19.Methods:Descriptive study nested in a cohort. Patients from the General Hospital of Cuernavaca who were hospitalized due to COVID-19 associated pneumonia and/or respiratory failure requiring supplemental oxygen or invasive/non-invasive assisted mechanical ventilation (AMV) were analyzed. All patients had a positive RT-PCR upon hospital admission, sampled under standardized conditions. The clinical and demographic data of the patients upon hospitalization were obtained from the instrument on a specific platform (SISVER) used on a national basis. Severe disease was considered as the need for any type of AMV. TCZ was used at 400-600 mg in two infusions (baseline and at 72 hours), Bari at 4 mg daily for 14 days. The outcomes were the need for AMV, death, or discharge. A p≤ 0.05 was considered statistically significant.Results:Data from 404 SARS-CoV2 positive patients were analyzed. 269 (65.9%) were men. The mean age of the patients was 57.5 years (18-94; SD 15.3). 59.6% of the patients had one or more comorbidities (Diabetes and Hypertension in most cases [31.8%]). 22.8% of the patients had a history of current or previous smoking. Mean hospital stay was 7.4 days (1-36; SD 5.9). 15.9% of the patients required invasive or non-invasive AMV. 11 patients were treated with TCZ and 30 patients received treatment with Baricitinib. 5 of the 11 patients with TCZ required AMV (all but one were intubated), but only 6 of the 30 (20%) with Bari required AMV (all except one received CPAP). The use of Baricitinib was correlated with a reduction in the use of AMV (p 0.01). 6 patients with TCZ were discharged due to improvement and 5 died. In the case of Bari, 19 improved and were discharged and 11 died, significantly correlating with lower mortality (p 0.05). The use TCZ was not associated with a reduced hospitalization (50% remained hospitalized for more than 10 days) but patients receiving Baricitinib had significantly shorter hospital stays (86.6% had a hospital stay of less than 10 days) than those receiving TCZ (p<0.0001).Conclusion:The patients that were treated with Baricitinib and required AMV most often improved with non-invasive CPAP while the majority of the patients under AMV receiving TCZ were treated with an invasive mode, although this was due in part to the fact that TCZ can be employed intravenously and is more practical for intubated patients in whom oral drug administration is limited. Baricitinib was significantly associated with a better outcome (hospital discharge due to improvement) and a significantly shorter hospital stay.References:[1]Kalil, A.C.; Patterson, T.F.; Mehta, A.K.; Tomashek, K.M.; Wolfe, C.R.; Ghazaryan, V.; Marconi, V.C.; Ruiz-Palacios, G.M.; Hsieh, L.; Kline, S.; et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N. Engl. J. Med. 2020.Acknowledgements:Thanks to B. Flores and M. Hernandez for their help with data collection.Disclosure of Interests:Daniel Xavier Xibille Friedmann Speakers bureau: Lilly, Abbvie, Paid instructor for: Lilly, Abbvie, Consultant of: Pfizer, Lilly, Sandra Miriam Carrillo Vazquez Speakers bureau: Roche, Novartis, Paid instructor for: Roche, Janssen, Consultant of: Roche, Janssen

TOWARD A COVID-19 SCORE-RISK ASSESSMENTS AND REGISTRY

ABSTRACTImportanceCritical care resources like ventilators, used to manage the current COVID-19 pandemic, are potentially inadequate. Established triage standards and guidelines may not contain the most appropriate severity assessment and outcome prediction models.ObjectivesDevelop a draft pandemic specific triage assessment score for the current COVID-19 pandemic. Design a website where initial Toward a COVID-19 Scores (TACS) can be quickly calculated and used to compare various treatment strategies. Create a TACS Registry where data and outcomes for suspected and confirmed COVID-19 patients can be recorded. Use the TACS Registry to develop an influenza epidemic specific database and score for use in future respiratory based epidemics.Design, Setting, ParticipantsRetrospective analysis of 3,301 ICU admissions with respiratory failure admitted to 41 U.S. Intensive Care Units from 2015-19. Independent external validation on 1,175 similar ICU Admissions using identical entry criteria from Barnes Jewish Hospital (BJH), Washington University from 2016-2019.Main OutcomesTACS was created with 16 readily available predictive variables for risk assessment of hospital mortality 24 hours after ICU Admission and the need for prolonged assisted mechanical ventilation (PAMV) (> 96 hours) at 24- and 48-hours post ICU admission.ResultsTACS achieved an Area Under the Curve (AUC) for hospital mortality after 24 hours of 0.80 in the development dataset; 0.81 in the internal validation dataset. At a probability of 50% hospital mortality, positive predictive value (PPV) was 0.55, negative predictive value (NPV) 0.89; sensitivity 22%, specificity 97%.For PAMV after 24 hours, the AUC was 0.84 in the development dataset, 0.81 in the validation dataset. For PAMV after 48 hours, the AUC was 0.82 in the development dataset, 0.78 in the validation dataset.In the external validation the AUC for TACS was 0.76 +/- 0.024. We launched a website that is scaled for mobile device use (https://covid19score.azurewebsites.net/) that provides open access to a user-friendly TACS Calculator for all predictions. We also designed a voluntary TACS Registry for collection of data and outcomes on ICU Admissions with COVID-19.Conclusions and RelevanceToward a COVID-19 score is a starting point for an epidemic specific triage assessment that could be used to evaluate various approaches to treatment. The TACS Registry provides the ability to establish a respiratory specific outcomes database that can be used to create a triage approach for future such pandemics.Key PointsQuestionCan a rapid epidemic specific risk assessment severity score and data and outcome repository be constructed in the midst of a pandemic.FindingsUsing development and validation datasets with ICU admissions similar to those developing COVID-19, developed an initial Toward a COVID-19 Score that could be used to compare various treatment approaches. Also launched an online facilitated data collection and outcome assessment registry for collection of a pandemic specific database so a new triage score could be created for use in the next pandemic.MeaningIn the midst of a pandemic rapid development of an epidemic specific triage score and a data registry for the creation of a new score for use in future pandemics appears feasible.