Development of an Open Source, Low-Cost Imaging System for Continuous Lung Monitoring

A lost-cost open-source electrical impedance tomography (EIT) device was equipped with a novel lidar based workflow to extract torso and electrode position which was then used in the EIT image reconstruction. EIT data was gathered from 9 healthy volunteers (5 male, 4 female) whilst undergoing a controlled breathing protocol. Four different reconstruction configurations were undertaken: a subject specific lidar based mesh versus a generic oval mesh, and subject specific lidar based electrode placements versus generic equal spaced electrode placements. Our results showed that torso shape error and electrode position errors can be drastically reduced with the lidar-based method allowing for the future utilization of patient-specific information. Good correlation was observed between volume delta and the EIT difference image. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

A microfluidic biosensor architecture for the rapid detection of COVID-19

The lack of enough diagnostic capacity to detect severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been one of the major challenges in the control the 2019 COVID pandemic;this led to significant delay in prompt treatment of COVID-19 patients or accurately estimate disease situation. Current methods for the diagnosis of SARS-COV-2 infection on clinical specimens (e.g. nasal swabs) include polymerase chain reaction (PCR) based methods, such as real-time reverse transcription (rRT) PCR, real-time reverse transcription loop-mediated isothermal amplification (rRT-LAMP), and immunoassay based methods, such as rapid antigen test (RAT). These conventional PCR methods excel in sensitivity and specificity but require a laboratory setting and typically take up to six hours to obtain the results whereas RAT has a low sensitivity (typically at least 3000 TCID50/ml) although with the results with 15 mins. We have developed a robust micro-electro-mechanical system (MEMS) based impedance biosensor fit for rapid and accurate detection of SARS-COV-2 of clinical samples in the field with minimal training. The biosensor consisted of three regions that enabled concentrating, trapping, and sensing the virus present in low quantities with high selectivity and sensitivity in 40 minutes using an electrode coated with a specific SARS-COV-2 antibody cross-linker mixture. Changes in the impedance value due to the binding of the SARS-COV-2 antigen to the antibody will indicate positive or negative result. The testing results showed that the biosensor's limit of detection (LoD) for detection of inactivated SARS-COV-2 antigen in phosphate buffer saline (PBS) was as low as 50 TCID50/ml. The biosensor specificity was confirmed using the influenza virus while the selectivity was confirmed using influenza polyclonal sera. Overall, the results showed that the biosensor is able to detect SARS-COV-2 in clinical samples (swabs) in 40 min with a sensitivity of 26 TCID50/ml.

Impedimetric Sensing: An Emerging Tool for Combating the COVID-19 Pandemic.

The COVID-19 pandemic revealed a pressing need for the development of sensitive and low-cost point-of-care sensors for disease diagnosis. The current standard of care for COVID-19 is quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). This method is sensitive, but takes time, effort, and requires specialized equipment and reagents to be performed correctly. This make it unsuitable for widespread, rapid testing and causes poor individual and policy decision-making. Rapid antigen tests (RATs) are a widely used alternative that provide results quickly but have low sensitivity and are prone to false negatives, particularly in cases with lower viral burden. Electrochemical sensors have shown much promise in filling this technology gap, and impedance spectroscopy specifically has exciting potential in rapid screening of COVID-19. Due to the data-rich nature of impedance measurements performed at different frequencies, this method lends itself to machine-leaning (ML) algorithms for further data processing. This review summarizes the current state of impedance spectroscopy-based point-of-care sensors for the detection of the SARS-CoV-2 virus. This article also suggests future directions to address the technology's current limitations to move forward in this current pandemic and prepare for future outbreaks.

Sensitive Detection of SARS-CoV-2 Spike Protein based on Electrochemical Impedance Spectroscopy of Fe3O4@SiO2-Au/GCE Biosensor

Highly contagious COVID-19 disease is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which poses a serious threat to global public health. Therefore, the development of a fast and reliable method for the detection of SARS-CoV-2 is an urgent research need. The Fe3O4@SiO2-Au is enriched with a variety of functional groups, which can be used to fabricate a sensitive electrochemical biosensor by biofunctionalization with angiotensin-converting enzyme 2 (ACE2). Accordingly, we developed a novel electrochemical sensor by chemically modifying a glassy carbon electrode (GCE) with Fe3O4@SiO2-Au nanocomposites (hereafter Fe3O4@SiO2-Au/GCE) for the rapid detection of S-protein spiked SARS-CoV-2 by electrochemical impedance spectroscopy (EIS). The new electrochemical sensor has a low limit detection (viz., 4.78 pg/mL) and a wide linear dynamic range (viz., 0.1 ng/mL to 10 μg/mL) for detecting the EIS response signal of S-protein. The robust Fe3O4@SiO2-Au/GCE biosensor has high selectivity, stability, and reproducibility for the detection of S-protein with good recovery of saliva samples.

Immunoaffinity biosensors for the detection of SARS-CoV-1 using screened Fv-antibodies from an autodisplayed Fv-antibody library.

The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-1) was demonstrated using screened Fv-antibodies for SPR biosensor and impedance spectrometry. The Fv-antibody library was first prepared on the outer membrane of E. coli using autodisplay technology and the Fv-variants (clones) with a specific affinity toward the SARS-CoV-1 spike protein (SP) were screened using magnetic beads immobilized with the SP. Upon screening the Fv-antibody library, two target Fv-variants (clones) with a specific binding affinity toward the SARS-CoV-1 SP were determined and the Fv-antibodies on two clones were named "Anti-SP1" (with CDR3 amino acid sequence: 1GRTTG5NDRPD11Y) and "Anti-SP2" (with CDR3 amino acid sequence: 1CLRQA5GTADD11V). The binding affinities of the two screened Fv-variants (clones) were analyzed using flow cytometry and the binding constants (KD) were estimated to be 80.5 ± 3.6 nM for Anti-SP1 and 45.6 ± 8.9 nM for Anti-SP2 (n = 3). In addition, the Fv-antibody including three CDR regions (CDR1, CDR2, and CDR3) and frame regions (FRs) between the CDR regions was expressed as a fusion protein (Mw. 40.6 kDa) with a green fluorescent protein (GFP) and the KD values of the expressed Fv-antibodies toward the SP estimated to be 15.3 ± 1.5 nM for Anti-SP1 (n = 3) and 16.3 ± 1.7 nM for Anti-SP2 (n = 3). Finally, the expressed Fv-antibodies screened against SARS-CoV-1 SP (Anti-SP1 and Anti-SP2) were applied for the detection of SARS-CoV-1. Consequently, the detection of SARS-CoV-1 was demonstrated to be feasible using the SPR biosensor and impedance spectrometry utilizing the immobilized Fv-antibodies against the SARS-CoV-1 SP.

Image Reconstruction for COVID-19 Using Multifrequency Electrical Impedance Tomography

Multifrequency electrical impedance tomography (MfEIT) is a technique that allows the visualization of images inside the body through the characterization of electrical impedance, conductivity or permissiveness in a given frequency range, as well as the characterization of body tissue analyzed. Usually, several alternating electrical currents are injected through electrodes connected to the surface of the body under study, and the resulting voltages are measured and stored for processing and obtaining an image. The image reconstruction algorithm uses the data set of measurements of applied currents and voltages measured at each electrode, calculating the distributions of conductivity, permittivity, or resistivity within the conductive volume studied. The reconstruction of images by direct methods is widely used in applications that require rapid reconstruction and lower computational cost, such as the monitoring of pulmonary mechanical ventilation in ICU beds in patients intubated due to COVID-19. In this chapter, we present the basic characteristics so that a wireless, low-cost, and portable MfEIT system can be implemented, as well as the definitions and modeling of the two-dimensional D-bar method for image reconstruction. Clinical parameters of patients diagnosed with COVID-19 are used to implement some reconstructions of images, as well as to bring a discussion about the efficiency of this technology for this clinical condition. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Development of gait rehabilitation devices: a review of the literature

A "Stroke" is a neurological disease due to poor blood flowing to the brain, resulting in body cell death. It is ranked second as the most common cause of death globally. The "World Health Organization" estimates that about 15 million people suffer a stroke annually. Most stroke survivors have gait disorders, and most patients cannot walk without assistance. Physiotherapy is crucial for stroke patients to recover and maintain their mobility, functionality, and well-being. In the last 20 years, the replacement of physiotherapists with wearable robotics has become essential due to the developing technology, the need for economic growth, and the challenging health circumstances around the world, such as the COVID-19 pandemic recently. Lower Limb Exoskeleton (LLE) represents the solution for stroke patients under such circumstances, though its performance is a critical challenge paid attention to in the industry. This challenge has motivated the researchers to investigate the application of gait rehabilitation. This review presents and discusses the developments in the control system of LLE over the last decade. It also explores the limitations, new directions, and recommendations in LLE development according to the literature.

Measurement of the Body Physical Parameters by Bioelectrical Impedance Method in Individuals Survived after Covid-19

Objective: The coronavirus disease 2019 (Covid-19) has significantly affected human health around the world, causing many complications. However, it is not fully understood how the body compositions of individuals affected in the short or long term after disease. In this study, we aimed to show the effects of Covid-19 on body composition and phase angle values, using Bioelectrical Impedance Analyzer. Methods: Subjects were selected from individuals in the 18-60 age group, who had survived COVID-19 disease. 33 individuals who had survived it 1-3 months ago, and 30 individuals who had survived it 3-6 months ago were included in the study. Results: Effects of COVID-19 on basal metabolism and body composition and the ratio of damaged cells in the body after the disease were determined. Basal metabolic rate, lean body mass, body cell mass, total body fluid, intracellular fluid, and phase angle values were found to be significantly changed in the 3-6 months range compared to that of 1-3 months. Conclusions: These results indicate that the basal metabolism and body composition parameters of the body become better, and the proportion of damaged cells decreases as time goes on after suffering COVID-19, reaching values close to normal in 1-3 months and quite better values in 3-6 months. It can be concluded that, although covid-19 influences body composition parameters and cell integrity in survivors of Covid 19 disease, these effects are limited to 3-6 months.

Development of Aptasensor for the Diagnosis of Covid-19

Objectives: The objective is to develop a low-cost, practical, portable aptasensor platform for the diagnosis of COVID-19. Materials -Methods: Amino-terminated aptamers to be used for the design of an aptasensor were synthesized by SELEX method, and interaction of aptamers with SARS-CoV-2 S1 protein was investigated by isothermal titration calorimetry (ITC). Gold electrodes were used to design the biosensor platform. After the electrode surface was functionalized with cysteamine, the amino-terminated aptamer was conjugated to the surface via glutaraldehyde crosslinker. Then, the surface characterization and analytical parameters of the designed sensing platform were determined by adding commercial S1 proteins on the surface using differential pulse voltammetry (DPV), cyclic voltammetry (CV) and impedance spectroscopy (EIS). To evaluate the working performance of the system, S1 proteins were added to the synthetic serum samples using the standard addition method and the measurements were repeated. Result(s): Surface characterization of the platform designed with EIS and CV measurements was performed and it was found that the modification was successfully performed. In addition, DPV results and analytical parameters of the platform (calibration plot, limit of detection(LOD) , repeatability, coefficient of variation) were determined and the working performance of system was evaluated. Moreover, working performance of the biosensor in real samples and its specificity for COVID -19 were determined by experiments with synthetic serum and influenza A and B proteins. Conclusion(s): According the results, the system has potential to be used for the detection of COVID -19, and also it can be rapidly adapted in different pandemic situations that may occur in the future.

Portable microfluidic impedance biosensor for SARS-CoV-2 detection.

Pandemics as the one we are currently facing, where fast-spreading viruses present a threat to humanity, call for simple and reliable methods to perform early diagnosis, enabling detection of very low pathogen loads even before symptoms start showing in the host. So far, standard polymerase chain reaction (PCR) is the most reliable method for doing so, but it is rather slow and needs specialized reagents and trained personnel to operate it. Additionally, it is expensive and not easily accessible. Therefore, developing miniaturized and portable sensors which perform early detection of pathogens with high reliability is necessary to not only prevent the spreading of the disease but also to monitor the effectiveness of the developed vaccines and the appearance of new pathogenic variants. Thus, in this work we develop a sensitive microfluidic impedance biosensor for the direct detection of SARS-CoV-2, towards a mobile point-of-care (POC) platform. The operational parameters are optimized with the aid of design-of-experiment (DoE), for an accurate detection of the viral antigens using electrochemical impedance spectroscopy (EIS). We perform the biodetection of buffer samples spiked with fM concentration levels and validate the biosensor in a clinical context of relevance by analyzing 15 real patient samples up to a Ct value (cycle threshold) of 27. Finally, we demonstrate the versatility of the developed platform using different settings, including a small portable potentiostat, using multiple channels for self-validation, as well as with single biosensors for a smartphone-based readout. This work contributes to the rapid and reliable diagnostics of COVID-19 and can be extended to other infectious diseases, allowing the monitoring of viral load in vaccinated and unvaccinated people to anticipate a potential relapse of the disease.

Modulation of pulmonary blood flow in patients with acute respiratory failure.

BACKGROUND: Impairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. METHODS: Single-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. RESULTS: Ten 65 [56-75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). CONCLUSIONS: The assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. METHODS: This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). DISCUSSION: As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. TRIAL REGISTRATION: ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

Determining Extracellular Water Effects in Mild and Severe COVID-19 Pneumonia Clinical Course by using the Bioimpedance Method

Aim: Coronavirus disease-2019 (COVID-19) pneumonia is characterized by a clinical picture showing similar features in severe patients. Some studies evaluate the pathophysiology, prognosis, and treatment of COVID-19 pneumonia. Different laboratory tests have been used to assess the severity and prognosis of rigorously ill COVID-19 patients in addition to clinical and radiological findings. There is no precise indicator for predicting prognosis. We aimed to analyze disease severity by using extracellular water (ECW) measurements. Methods: Extracellular water values and cardiac parameters as cardiac output (CO), and stroke volume (SV) measurements of patients were performed using a non-invasive, easy-to-use, validated device non-invasive cardiac system (NICaS) within the first 2 h after admission. Hemodynamic parameters and ECW values were measured by connecting the NICaS device to make 12 measurements for 2 h at 5 min intervals during admission to service and intensive care patients. Results: Comparing the ward and intensive care groups, there was not any statistically significant difference found between demographic data and ECW, SV, and CO measurements. Conclusion: Although we could not find a statistically significant difference between our measurements, we believe that the NICaS device can play a significant role in the fluid treatment of COVID-19 patients. © 2023 by the Istanbul Haseki Training and Research Hospital.

Differences In Lung Fluid Quality Between Decompensated Heart Failure Patients And Covid-19 Patients- Results Of The Impedance-corona Trial

Introduction: Hospitalized COVID-19 patients commonly develop pulmonary complications and respiratory insufficiency. Prediction of respiratory deterioration in hospitalized COVID-19 patients is an unmet goal. Aim(s): To assess monitoring of lung fluid status of hospitalized COVID-19 patients to predict respiratory deterioration and prognosis. ClinicalTrials.gov Identifier: NCT04406493. Method(s): Study population comprised 51 patients hospitalized in Hillel Yaffe Medical Center with COVID-19 infection. Patient lung fluid status was monitored by repeat measurements of the lung impedance (LI), a technique found to be very effective for monitoring and guiding treatment of heart failure patients. Decreasing LI reflects lung fluid accumulation. Clinical and laboratory parameters, chest X-ray and LI level were recorded during hospitalization. Result(s): Of 51 patients hospitalized for COVID-19 infection (37- men and 14- women, 55.7+/-12.6 years-old), 46 were discharged alive after successful treatment and of these 27 returned for follow-up evaluation 3-6 months after discharge. In these patients' admission LI was 72.6+/-18.4 Ohms (Figure 1) and discharge LI was 83.8+/-20.7 Ohms, which is 15% higher than the admission value (p< 0.04). LI at the follow up visit was surprisingly low (63.7+/-15 Ohms), or 31.6% lower than discharge value (p<0.01, figure 1). At follow up, examination of the patients and the NT-proBNP tests were within normal limits. Using our previous experience we calculated the normal ("dry") LI based on the age, sex, weight, height and anthropology of the chest. The calculated values of the normal LI of patients in time of post-discharge visits were exactly same as measured. Therefore, the LI values of patients in time of hospitalization were higher than their normal values. This finding contrasts with our experience with heart failure patients, where decreasing LI reflects lung fluid accumulation. The possible explanation of this finding is that the lung fluid of COVID-19 patients, containing a high concentration of proteins, has different conductivity properties than the lung fluid of heart failure patients. Conclusion(s): Decreasing of LI level at post-discharge visits of COVID-19 patients 3-6 months after hospitalization differs significantly from the pattern in heart failure patients.Copyright © 2022

Automatic Analysis of Isothermal Amplification via Impedance Time-Constant-Domain Spectroscopy: A SARS-CoV-2 Case Study

The development of sensitive and affordable testing devices for infectious diseases is essential to preserve public health, especially in pandemic scenarios. In this work, we have developed an attractive analytical method to monitor products of genetic amplification, particularly the loop-mediated isothermal amplification reaction (RT-LAMP). The method is based on electrochemical impedance measurements and the distribution of relaxation times model, to provide the so-called time-constant-domain spectroscopy (TCDS). The proposed method is tested for the SARS-CoV-2 genome, since it has been of worldwide interest due to the COVID-19 pandemic. Particularly, once the method is calibrated, its performance is demonstrated using real wastewater samples. Moreover, we propose a simple classification algorithm based on TCDS data to discriminate among positive and negative samples. Results show how a TCDS-based method provides an alternative mechanism for label-free and automated assays, exhibiting robustness and specificity for genetic detection.

A Low-cost Handheld Reconfigurable Impedimetric Readout System for Diagnostics of Viral Infections

This paper presents a portable impedimetric biosensor for detecting infectious diseases such as SARS-CoV-2 Infections. A bio-ready sensing electrode functionalized with SARS-CoV-2 nucleocapsid antibody was employed to quantitatively convert the concentration of nucleocapsid protein (N-protein) into impedance changes. In this paper, we proposed a readout system with a dynamic input range of 200 Ωto 1 MΩmagnitude and 0 to 180°phase. The resolution of this device is 1% and 6.5°for measuring the magnitude and phase, respectively. Herein we demonstrate and discuss the proposed system’s functionality, sensitivity, and selectivity using the clinical swab samples. As per these results, this readout system is suitable for the detection of N-protein ranging up to 10,000 pg/mL with a resolution of 56 fg/mL. The proposed impedimetric sensing system can be adopted for the detection of infectious diseases in the future. This low-cost (<$80) device using off-the-shelf is a unique candidate for batch production purposes during urgent pandemic situations. IEEE

Customizable Fabrication Process for Flexible Carbon-Based Electrochemical Biosensors

In recent research, 3D printing has become a powerful technique and has been applied in the last few years to carbon-based materials. A new generation of 3D-printed electrodes, more affordable and easier to obtain due to rapid prototyping techniques, has emerged. We propose a customizable fabrication process for flexible (and rigid) carbon-based biosensors, from biosensor design to printable conductive inks. The electrochemical biosensors were obtained on a 50 µm Kapton® (polyimide) substrate and transferred to a 500 µm PDMS substrate, using a 3D-extrusion-based printing method. The main features of our fabrication process consist of short-time customization implementation, fast small-to-medium batch production, ease of electrochemical spectroscopy measurements, and very good resolution for an extrusion-based printing method (100 µm). The sensors were designed for future integration into a smart wound dressing for wound monitoring and other biomedical applications. We increased their sensibility with electro-deposited gold nanoparticles. To assess the biosensors' functionality, we performed surface functionalization with specific anti-N-protein antibodies for SARS-CoV 2 virus, with promising preliminary results.

Monitoring of the lung fluid status in hospitalized COVID-19 patients for predicts outcome. Results of the IMPEDANCE-Corona Trial

Introduction: Prediction of the clinical deterioration in hospitalized COVOD-19 patients is an unmet goal. Aim(s): To assess monitoring of lung fluid status of hospitalized COVID-19 patients as a tool to predict clinical respiratory deterioration and prognosis. Method(s): The present study population comprised 51 patients hospitalized in our medical center with COVID-19 infection. The lung fluid status of patients was monitored by repeat measurements the lung impedance (LI). The LI technique was found to be a very effective tool for monitoring and guiding the treatment of a heart failure patients. Decreasing LI reflects lung fluid accumulation. Clinical and laboratory parameters, chest X-ray (CXR) and LI level were recorded during hospitalization. Result(s): Of the 51 patients hospitalized for COVID-19 infection (37 men and 14 women, 55.7+/-12.6 years old), 46 were discharged after successful treatment (Group 1) and 5 (9.8%) died during hospitalization (Group 2). The LI kinetics during hospitalization demonstrated a different pattern between groups (Figure 1, p<0.01). In group 1 patients, a small LI decrease (-3.5+/-4.3%, p=0.7) during the first 4 days (median = 2.2 days, [Q1- 3: 1-3.7 days]) of hospitalization was noted. Following this, LI increased progressively until discharge (+20.3+/-12.3%, p<0.01). Among group 2 patients, LI decreased progressively during hospitalization. Mechanical ventilation was initiated at the eighth day [median = 8, Q1-3: 4-12 days] when LI decreased by 18.2+/-3.8% in comparison with the admission level (p<0.01). Deaths occurred at 12.4+/-2.7 days (median = 12 days) after admission. Multivariate Cox regression analysis of clinical, laboratory and CXR variance has shown that the degree of LI decrease during hospitalization is the most reliable predictor of death (hazard ratio: 1.36 [1.04-1.79], p<0.04). Conclusion(s): The combination of progressively decreasing LI after 4 days of hospitalization for COVID-19 infection and an LI decrease >15% is the most reliable predictor of death.

Po251 / #854 Noninvasive Closed Loop Diaphragm Stimulation for Ventilated Icu Patients: E-Poster Viewing

Introduction: Many COVID-19 patients need prolonged artificial ventilation. Skeletal muscle wastes rapidly when deprived of neural activation, and in ventilated patients the diaphragm muscle begins to atrophy within 24 hours (ventilator induced diaphragmatic dysfunction, VIDD). This profoundly weakens the diaphragm, complicating the weaning of the patient off the ventilator, and increasing the risk of complications such as bacterial pneumonia. 40% of the total duration of mechanical ventilation in ITU patients is accounted for by the weaning period, after the initial illness has resolved. Prevention of VIDD would therefore both improve individual outcomes, and also release ITU capacity. We aim to prevent VIDD by exercising the diaphragm with electrical stimulation of the nerves that control it. Evidence suggests that muscle wasting can be prevented by quite low levels of exercise (e.g. 200 contractions per day). Materials / Methods: The diaphragm is activated by the phrenic nerves, formed from branches of the C3-C5 nerve roots in the neck. These nerves may be electrically stimulated in the lower neck. An electrode array is positioned on each side of the neck using surface landmarks. The system automatically determines the best electrode to use in each array. Sensors built into the ventilatory circuit are monitored both to match stimulation to the respiratory cycle and to determine the effects of stimulation. Result(s): We have designed and built a prototype system for unsupervised noninvasive phrenic nerve stimulation. The system delivers one contraction every 7 minutes, synchronised to early inspiration so as not to disrupt ventilation. Electrode impedances are measured before each stimulus, and the closed loop system continuously monitors the effects of stimulation on airflow and adjusts stimulation parameters to compensate for changes in coupling, for example due to head movement. Discussion(s): This stimulator system overcomes several limitations of existing solutions, namely the resource implications and risk profile of invasive electrodes, and the requirement for supervised operation. While invasive systems are applied selectively for these reasons, routine use of our system can be envisaged. This system was inspired by COVID-19 patients but is not limited to them, and has broad applicability to ventilated intensive care patients in general, for example patients with traumatic brain injury. Conclusion(s): Non-invasive stimulation of the phrenic nerves using pressure-free skin surface electrodes is feasible and safe. It offers the potential for prevention of VIDD and thereby faster ventilator weaning and shorter stay on ITU. Clinical trials are planned in 2022. Learning Objectives: After this presentation delegates should be aware of: 1. Ventilation induced diaphragm dysfunction (VIDD) and its importance in patients having lengthy periods of ventilation, as in many cases of COVID-19. 2. The fact that low levels of activity can maintain the condition of skeletal muscles including the diaphragm muscle 3. The potential for noninvasive stimulation of the phrenic nerves to provide 'diaphragm exercise' and prevent VIDD. Keywords: phrenic nerve stimulation, diaphragm, ventilation, COVID-19Copyright © 2022