The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

The severity of SARS-CoV-2 infection in K18-hACE2 mice is attenuated by a novel steroid-derivative in a gender-specific manner.

BACKGROUND AND PURPOSE: COVID-19 infections caused by SARS-CoV-2 disseminated through human-to-human transmission can evoke severe inflammation. Treatments to reduce the SARS-CoV-2-associated inflammation are needed and are the focus of much research. In this study, we investigated the effect of N-ethyl-N'-[(3ß,5α)-17-oxoandrostan-3-yl] urea (NEOU), a novel 17α-ketosteroid derivative, on the severity of COVID-19 infections. EXPERIMENTAL APPROACH: Studies were conducted in SARS-CoV-2-infected K18-hACE2 mice. KEY RESULTS: SARS-CoV-2-infected K18-hACE2 mice developed severe inflammatory crises and immune responses along with up-regulation of genes in associated signalling pathways in male more than female mice. Notably, SARS-CoV-2 infection down-regulated genes encoding drug metabolizing cytochrome P450 enzymes in male but not female mice. Treatment with NEOU (1 mg·kg-1 ·day-1 ) 24 or 72 h post-viral infection alleviated lung injury by decreasing expression of genes encoding inflammatory cytokines and chemokines while increasing expression of genes encoding immunoglobins. In situ hybridization using RNA scope™ probes and immunohistochemical assays revealed that NEOU increased resident CD169+ immunoregulatory macrophages and IBA-1 immunoreactive macrophage-dendritic cells within alveolar spaces in the lungs of infected mice. Consequentially, NEOU reduced morbidity more prominently in male than female mice. However, NEOU increased median survival time and accelerated recovery from infection by 6 days in both males and females. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that SARS-CoV-2 exhibits gender bias by differentially regulating genes encoding inflammatory cytokines, immunogenic factors and drug-metabolizing enzymes, in male versus female mice. Most importantly, we identified a novel 17α-ketosteroid that reduces the severity of COVID-19 infection and could be beneficial for reducing impact of COVID-19.

Effect of folic acid in patients with lung damage caused by coronavirus SARS-CoV-2

Aim of study. To evaluate the influence exerted by additional use of a fixed combination of folic acid with pyridoxine hydrochloride and cyanocobalamin in complex therapy for hospitalised patients with COVID-19-associated lung damage on parameters of inflammation and clinical outcomes. Material and methods. A comparative prospective interventional study included 117 patients with a lung lesion volume caused by the SARS-CoV-2 coronavi-rus corresponding to CT-1 and CT-2. The study group included 78 patients who additionally received a fixed combination of 5mg folic acid, 4mg pyridoxine hydrochloride, and 6mug cyanocobalamin three times a day in combination with standard therapy. The comparison group included 39 patients. Results. By days 14-21 of hospitalisation, the main group showed a decrease in the proportion of patients with CT symptoms of "cobblestone appearance" by 26% (p = 0.005) and an increase in the proportion of patients with transformation of viral lung lesions into areas of consolidation of the pulmonary parenchyma by 23% (p <0.001). The effect of a fixed combination of folic acid with vitamins B6, B12 on the achievement of the level of C-reactive protein <20 mg / l by day 7 depending on the red blood parameters and the number of platelets was established (likelihood ratio test in the logistic regression model: 13.925;P = 0.084) as well as the shortening of the time period required to reach the first negative result of the SARS-CoV-2 RNA test (in the linear regression model, R = 0.437;R2 = 0.191;F = 4.552;p = 0.006). Conclusion. The use of a fixed combination of folic acid with vitamins B6, B12 for patients with COVID-19 is associated with earlier achievement of positive dynamics in CT symptoms of lung damage. The additional use of these micronutrients in combination with restoration of red blood count and platelet count improves the odds ratio of an early decrease in serum C-reactive protein, negative result of the SARS-CoV-2 RNA test.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

Lethality of SARS-CoV-2 infection-a comparative autopsy study focusing on COVID-19 development and virus variants.

AIMS: Different SARS-CoV-2 variants are driving various waves of infection of the corona pandemic. Official statistics provide no information on who died due to coronavirus disease 2019 (COVID-19) or an alternative disease during which SARS-CoV-2 infection was detected. The current study aims at addressing the effect of the different variants evolving during the pandemic on fatal outcomes. METHODS AND RESULTS: Standardised autopsies were performed on 117 people who died of a SARS-CoV-2 infection and the findings were interpreted in clinical and pathophysiological contexts. The typical histological sequence of COVID-19-related lung injury was detected independently of the disease-causing virus variant, but was significantly less common (50 versus 80-100%) and less severe in cases infected by omicron variants compared to precedent variants (P < 0.05). COVID-19 was less often the leading cause of death following omicron infection. Extrapulmonary manifestations of COVID-19 did not contribute to death in this cohort. Lethal COVID-19 may occur after complete SARS-CoV-2 vaccination. Reinfection was not the cause of death in any of the autopsies of this cohort. CONCLUSION: Autopsies represent the gold standard in determining the cause of death after SARS-CoV-2 infection and autopsy registers are currently the only available data source allowing for evaluation of which patients died of COVID-19 or with SARS-CoV-2 infection. Compared to previous variants, infection with an omicron variant affected the lungs less frequently and resulted in less severe lung disease.

Human Lung Non-Invasive Anomaly Detection through UWB Microwave Imaging and Diagnosis of COVID-19: A Possible Application

This study shows a prototype for detecting lung effects using microwave imaging. Continuous monitoring of pulmonary fluid levels is one of the most successful approaches for detecting fluid in the lung;early Chest X-rays, computational tomography (CT)-scans, and magnetic resonance imaging (MRI) are the most commonly used instruments for fluid detection. Nonetheless, they lack sensitivity to ionizing radiation and are inaccessible to the general public. This research focuses on the development of a low-cost, portable, and noninvasive device for detecting Covid-19 or lung damage. The simulation of the system involved the antenna design, a 3D model of the human lung, the building of a COMSOL model, and image processing to estimate the lung damage percentage. The simulation consisted of three components. The primary element requires mode switching for four array antennas (transmit and receive). In the paper, microwave tomography was used. Using microwave near-field imaging, the second component of the simulation analyses the lung's bioheat and electromagnetic waves as well as examines the image creation under various conditions;many electromagnetic factors seen at the receiving device are investigated. The final phase of the simulation shows the affected area of the lung phantom and the extent of the damage. © 2023 IEEE.

Evaluation of the Sensitivity of Prominent Biomarkers Involvement in Diagnosing the Severity of Lung Damage in Patients with COVID-19.

Background: COVID-19 has become the greatest pandemic of the century. Considering the role of some hematologic and biochemical factors and their alterations due to the activity of the immune system, the current study aimed to evaluate LDH/CRP/ESR/RDW in patients with COVID-19 and their relationship with the severity of lung involvement based on CT scan findings. Methods: In this cross-sectional study, some biomarkers (LDH/CRP/ESR/RDW) were measured in 158 patients who were admitted to the intensive care unit (ICU) or hospitalized in the infectious diseases ward of Rasoul-e-Akram and Firoozgar hospitals or attended to the outpatient clinics. The diagnosis was confirmed by a positive RT-PCR test in all patients. The severity of lung involvement was determined by CT scan findings for comparison. Data were collected and analyzed through SPSS version 22. Results: Regarding the severity of lung damage according to the CT scan, 17.7% of the patients were normal, 19% had less than 25% involvement, 17% had 25% -50% involvement, 33.5% had 50% -75% involvement, and 12% had more than 75% involvement. Considering the increasing severity of lung damage based on CT scans, the levels of RDW, ESR, CRP, and LDH significantly increased in parallel. The diagnostic value of RDW (cut-off point: 12.6, Sen: 73.1% (95%CI: 65.1-79.5), Sp: 53.6% (95%CI: 45.7-61.7), ESR (cut-off point: 49, Sen: 46.9% (95%CI: 38.2-54.5)), Sp: 85.7% (95%CI: 789.-90.5)), CRP (cut-off point: 23, Sen: 62.8% (95%CI: 54.6-70.4), Sp: 77.7% (95%CI: 70.3-84.1)) and LDH (cut-off point: 550, Sen: 65.1% (95%CI: 57.2-72.5), Sp: 85.7% (95%CI: 78.9-90.5)) were significant in diagnosing the severity of lung involvement (P < 0.05). Conclusion: The use of RDW, ESR, CRP, and LDH biomarkers could be effective in predicting the severity of lung damage in patients with COVID-19.

Residual Lung Abnormalities Following COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID Study.

RATIONALE: Shared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage. OBJECTIVES: The UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata. METHODS: The Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up. MEASUREMENTS AND MAIN RESULTS: The interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLco<80% (RR 1·25 95%CrI 1·00; 1·56) and severe admission requiring ventilation support (RR 1·27 95%CrI 1·07; 1·55). In the remaining 3491 people, moderate to very-high risk of residual lung abnormalities was classified in 7·8%, post-hospitalization prevalence was estimated at 8.5% (95%CrI 7.6%; 9.5%) rising to 11.7% (95%CrI 10.3%; 13.1%) in sensitivity analysis. CONCLUSIONS: Residual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Impact of supplemental vitamins and natural honey for treatment of COVID-19: A review

Abstract The main aim of the paper is to assess whether vitamin C, vitamin D, and natural honey can be administered in the course of the COVID-19 pandemic for promising in line methods with recent evidence. Both systematic literature and clinical trial identification were conducted by searching various databases. A total 58 articles and 29 clinical trials were selected wherein 11 for vitamin C, 16 for vitamin D, and 2 for natural honey were identified for analysis. The high doses of vitamin C (i.e. '200 mg/kg body weight/day, divided into 4 doses') has been found to reduce COVID-19 lung damage, various flu infections. Additionally, the high doses of vitamin C can shorten around 7.8% stay in the intensive care unit. At the same time, vitamin D can effectively protect from lung injury and acute respiratory infections whereas vitamin D deficiency severely affects 75% of the institutionalized people (serum 25(OH) D < 25 nmol/L). Meanwhile, natural honey which contains proteins (0.1-0.4%); ash (0.2%); water (15-17%) has potential antiviral effects and the ability to improve immunity. Therefore, the administration of vitamins and honey is the promising evidence-based approach for reducing fatalities, saving lives, and bringing the COVID-19 pandemic to a rapid end. It is believed that the utilization of vitamin C, vitamin D, and natural honey with the current treatment may be effective in treating COVID-19-caused fatal complications such as pneumonia. Therefore, high-level clinical studies are required on COVID-19 to administrate the effects of vitamins and natural honey.

Role of Mesenchymal Stem Cells and Extracellular Vesicles in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic disease that leads to disability and death within 5 years of diagnosis. Pulmonary fibrosis is a disease with a multifactorial etiology. The concept of aberrant regeneration of the pulmonary epithelium reveals the pathogenesis of IPF, according to which repeated damage and death of alveolar epithelial cells is the main mechanism leading to the development of progressive IPF. Cell death provokes the migration, proliferation and activation of fibroblasts, which overproduce extracellular matrix, resulting in fibrotic deformity of the lung tissue. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis. MSCs, and EVs derived from MSCs, modulate the activity of immune cells, inhibit the expression of profibrotic genes, reduce collagen deposition and promote the repair of damaged lung tissue. This review considers the molecular mechanisms of the development of IPF and the multifaceted role of MSCs in the therapy of IPF. Currently, EVs-MSCs are regarded as a promising cell-free therapy tool, so in this review we discuss the results available to date of the use of EVs-MSCs for lung tissue repair.

Respiratory dispositive with intelligent shape-memory alloy wires to help artificial ventilation during sleep for SARS-CoV patients

This chapter discusses in detail the relationship between obstructive sleep apnea (OSA) and COVID-19 complications, the causative mechanisms, the effect of COVID-19 on the diagnosis of OSA, and the effect on the management and treatment of OSA during this pandemic. The restrictions imposed due to the pandemic have led to higher levels of mental stress, depression, and stress, increasing the burden of mental health and affecting sleep patterns, disrupting daily life, and having a significant effect on sleep health. The use of shape-memory alloys in devices to support breathing contributes to increasing the quality of service provided by this equipment primarily by reducing the noise produced by drive motors, but also by lowering the price. © 2022 Elsevier Inc. All rights reserved.

Recent Advances in Marine Microalgae Production: Highlighting Human Health Products from Microalgae in View of the Coronavirus Pandemic (COVID-19)

Blue biotechnology can greatly help solve some of the most serious social problems due to its wide biodiversity, which includes marine environments. Microalgae are important resources for human needs as an alternative to terrestrial plants because of their rich biodiversity, rapid growth, and product contributions in many fields. The production scheme for microalgae biomass mainly consists of two processes: (I) the Build-Up process and (II) the Pull-Down process. The Build-Up process consists of (1) the super strain concept and (2) cultivation aspects. The Pull-Down process includes (1) harvesting and (2) drying algal biomass. In some cases, such as the manufacture of algal products, the (3) extraction of bioactive compounds is included. Microalgae have a wide range of commercial applications, such as in aquaculture, biofertilizer, bioenergy, pharmaceuticals, and functional foods, which have several industrial and academic applications around the world. The efficiency and success of biomedical products derived from microalgal biomass or its metabolites mainly depend on the technologies used in the cultivation, harvesting, drying, and extraction of microalgae bioactive molecules. The current review focuses on recent advanced technologies that enhance microalgae biomass within microalgae production schemes. Moreover, the current work highlights marine drugs and human health products derived from microalgae that can improve human immunity and reduce viral activities, especially COVID-19. © 2022 by the authors.

Evaluation of Lactate Dehydrogenase (LDH) in predicting the severity of lung involvement and pneumomediastinum in hospitalized COVID-19

Background: COVID-19 is a health crisis that triggered the need to find a rapid and sensitive tool to screen populations with a high risk of complications. Lactate Dehydrogenase (LDH) is an enzyme found in almost all body cells, particularly pneumocytes, and appears to be associated with worst outcome. Pneumomediastinum (PM), which results from ruptured alveoli, can occur in non-ventilated patients. Acute pneumocytes injury induces the release of serum LDH. Objective: This study evaluates the role of baseline serum LDH levels in predicting COVID-19 lung necrosis. Methods: This retrospective study was conducted among 524 COVID-19 patients admitted to Hôtel-Dieu de France university hospital, Lebanon, between March 2020 and March 2021. Baseline serum LDH was retrieved from patients’ medical records. Radiological severity outcomes were assessed at admission and during follow-up by non-contrast computed tomography (NCCT) of the chest. Results: The mean age of participants was 63 ±16 years, with 359 males (68.5%) and median (IQR) LDH levels upon admission of 328 (248-430). LDH was correlated with lobar involvement at both admission and NCCT follow-up (Spearman’s rho 0.527 and 0.264, respectively) and the development of a PM (p=0.035) in 3% of the patients. Using ROC analysis, a baseline LDH value higher than 395 U/L was associated with the presence of a PM on admission and follow up chest CT, with a sensitivity of 75% and a specificity of 60.1%. Conclusion: Baseline LDH levels could serve as a tool for early diagnosis of severe pulmonary injury with poor radiological outcomes in hospitalized COVID-19 patients. o Fundamento: El COVID-19 es una crisis sanitaria que desencadenó la necesidad de encontrar una herramienta rápida y sensible para el cribado de poblaciones con alto riesgo de complicaciones. La lactato deshidrogenasa (LDH) es una enzima que se encuentra en casi todas las células del cuerpo, particularmente en los neumocitos, y parece estar asociada con el peor resultado. El neumomediastino (PM), que resulta de la ruptura de los alvéolos, puede ocurrir en pacientes no ventilados. La lesión aguda de neumocitos induce la liberación de LDH sérica. Objetivo: Este estudio evalúa el papel de los niveles séricos basales de LDH en la predicción de la necrosis pulmonar por COVID-19. Métodos: Este estudio retrospectivo se realizó entre 524 pacientes con COVID-19 ingresados en el hospital universitario Hôtel-Dieu de France, Líbano, entre marzo de 2020 y marzo de 2021. La LDH sérica basal se recuperó de los registros médicos de los pacientes. Los resultados de gravedad radiológica se evaluaron al ingreso y durante el seguimiento mediante tomografía computarizada (TCNC) sin contraste del tórax. Resultados: La edad media de los participantes fue de 63 ±16 años, con 359 varones (68,5%) y mediana (IQR) niveles de LDH al ingreso de 328 (248-430). La LDH se correlacionó con la afectación lobar tanto al ingreso como al seguimiento de la NCCT (rho de Spearman 0,527 y 0,264, respectivamente) y el desarrollo de un PM (p=0,035) en el 3% de los pacientes. Mediante el análisis ROC, se asoció un valor basal de LDH superior a 395 U/L con la presencia de un PM al ingreso y seguimiento de la TC de tórax, con una sensibilidad del 75% y una especificidad del 60,1%. Conclusión: Los niveles basales de LDH podrían servir como una herramienta para el diagnóstico precoz de lesión pulmonar grave con malos resultados radiológicos en pacientes hospitalizados con COVID-19.

Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study.

BACKGROUND: Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. OBJECTIVE: This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. METHODS: We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. RESULTS: The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. CONCLUSIONS: From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37426.

An Entropy-Based Measure of Complexity: An Application in Lung-Damage.

The computed tomography (CT) chest is a tool for diagnostic tests and the early evaluation of lung infections, pulmonary interstitial damage, and complications caused by common pneumonia and COVID-19. Additionally, computer-aided diagnostic systems and methods based on entropy, fractality, and deep learning have been implemented to analyse lung CT images. This article aims to introduce an Entropy-based Measure of Complexity (EMC). In addition, derived from EMC, a Lung Damage Measure (LDM) is introduced to show a medical application. CT scans of 486 healthy subjects, 263 diagnosed with COVID-19, and 329 with pneumonia were analysed using the LDM. The statistical analysis shows a significant difference in LDM between healthy subjects and those suffering from COVID-19 and common pneumonia. The LDM of common pneumonia was the highest, followed by COVID-19 and healthy subjects. Furthermore, LDM increased as much as clinical classification and CO-RADS scores. Thus, LDM is a measure that could be used to determine or confirm the scored severity. On the other hand, the d-summable information model best fits the information obtained by the covering of the CT; thus, it can be the cornerstone for formulating a fractional LDM.

Blockchain Assisted Disease Identification of COVID-19 Patients with the Help of IDA-DNN Classifier.

Globally, millions of people were affected by the Corona-virus disease-2019 (COVID-19) causing loads of deaths. Most COVID-19 affected people recover in a few spans of weeks. However, certain people even those with a milder variant of the disease persist in experiencing symptoms subsequent to their initial recuperation. Here, a novel Block-Chain (BC)-assisted optimized deep learning algorithm, explicitly improved dragonfly algorithm based Deep Neural Network (IDA-DNN), is proposed for detecting the different diseases of the COVID-19 patients. Initially, the input data of the COVID-19 recovered patients are gathered centered on their post symptoms and their data is amassed as a BC for rendering security to the patient's data. After that, the disease identification of the patient's data is performed with the aid of system training. The training includes '4' disparate datasets for data collection, and then, performs preprocessing, Feature Extraction (FE), Feature Reduction (FR), along with classification utilizing ID-DNN on the gathered inputted data. The IDA-DNN classifies '2' classes (presence of disease and absence of disease) for every type of data. The proposed method's outcomes are examined as well as contrasted with the other prevailing techniques to corroborate that the proposed IDA-DNN detects the COVID-19 more efficiently.

INFLUENCE OF ANTIBIOTIC THERAPY ON INDICATORS OF ENDOTOXINEMIA AND SYSTEMIC INFLAMMATION IN ACUTE SARS-COV-2 LUNG DAMAGE

Background. Prescribing antibacterial drugs for the treatmentofa new coronavirus infection at the outpatient stage is often unreasonable and can also lead to an aggravation of the patient's condition due to the effect of this group of drugs on the intestinal microflora and lead to other undesirable effects. The aim: to assess the level of lipopolysaccharide-binding protein and indicators of systemic inflammation in patients with moderate viral SARS-CoV-2 lung disease on the background of antibiotic therapy. Materials and methods. 60 patients hospitalized in the infectious diseases departmentwitha positive PCRresultfor SARS-CoV-2in the age group 44-70 years oldwere examined. The patients were divided into 2 groups: group 1 (n = 26) - patients who didnotreceive antibacterialdrugs atthe outpatientstage, group 2 (n= 34)- patients who receivedantibiotic therapy. The control group was also selected(n= 20). Patients underwent a study of the level of lipopolysaccharide-binding protein (LBP), ferritin and C-reactive protein in the peripheral blood. Results. Inthe groupofpatientswithnewcoronavirusinfectionwhowereadmittedto the inpatientstage oftreatmentandreceivedantibacterialtherapy atthe outpatient stage, a significantly higher levels of LBP - 37.3 [13.8;50.4] µg/ml (p < 0.05) and ferritin- 276.00 [184.00;463.00] µg/ml (p < 0.05)were revealed, comparedwith group 1 and the control group. Conclusions. In the group of patients who received antibiotic therapy at the outpatient stage, a significantly higher level of LBP was revealed compared to the group in which this group of drugs was not used. These results indicate the possible impact of uncontrolled and early intake of antibacterial drugs on the gut microbiome andintestinal permeability, andalso prove the needfor a more responsible approach to the choice of starting therapy for new coronavirus infection. © 2022 by the authors.

Study of UWB Near Field Microwave Imaging System for the Diagnosis of Lungs Damage Due to Fluid Accumulations

Lung damages, which is the leading cause of cancer and Covid-19 related death worldwide, can be better treated, and patients' chances of survival increased with early detection and diagnosis. PET (positron emission tomography), cone beam CT, Low dose helical CT, are advanced lung imaging techniques that allow for early diagnosis of smaller pulmonary nodules than normal chest radiography, but with ionizing radiation effect and being costly. In the field of imaging technology, microwave imaging has long been researched in the field of breast and brain. This study presents a review, conducts a feasibility study, and validates the concept of imaging the lungs in a similar manner to the breast and brain. The analysis includes designing a 3D human lung model, microwaves' various elements and factors inspection through the human body using holographic near field imaging, and image processing to estimate the percentage of lung damage. The safety and ionization exposure were also taken into consideration during the overall experiment. The use of microwave energy in various lung diseases is examined, and the basis for fluid detection utilizing microwave water content accumulation is also addressed compared to normal tissues. © 2022 IEEE.

Association of Chest CT Severity Scores and Vaccination Status in COVID-19 Disease: A Cross-sectional Study

Introduction: Coronavirus Disease 2019 (COVID-19) has emerged as a pandemic with substantial morbidity and mortality. While global efforts towards mitigating the infection are focused on the vaccination of population, studies are warranted to prove the efficacy of vaccine in prevention of infection or reducing the severity of infection in affected patients. The 25-point High Resolution Computed Tomography (HRCT) severity score has proved to be an effective tool in estimating the severity of lung infection and correlates with laboratory parameters and disease outcome. The HRCT scores hence provide an objective evidence to prove the efficacy of vaccines in vaccinated individuals by assessing the extent of lung involvement. Aim: To compare the chest CT severity score in vaccinated and unvaccinated COVID-19 infected patients. Materials and Methods: This cross-sectional study was conducted in the Department of Radiology, at Sri Jayadeva Institute of Cardiovascular Sciences and Research, Mysuru, Karnataka, India. The data of HRCT scores and vaccination status was collected during the month of April 2021 from patients who were suspected to have COVID-19 infection and underwent a chest HRCT scan. The severity of lung infection in vaccinated and unvaccinated individuals was compared based on the HRCT scores and the association between these variables were analysed. The association between the respective variables were studied using Fischer's-exact and Kruskal-Wallis tests. Results: The study involved a total of 178 subjects (males were 98), where 127 (71.3%) were unvaccinated and 51 (28.6%) were vaccinated with one or both doses {Covaxin (Bharat Biotech) vaccine or Covishield (Oxford-AstraZeneca) vaccine approved by Emergency Use Authorisation (EUA)}. The frequency of disease was least in 14 (7.9%) among fully vaccinated subjects. Severe COVID-19 associated pneumonia with severity score of 18 or more was seen in 7% of unvaccinated individuals, while none of the partial/fully vaccinated individuals had severe disease. The median CT severity score was significantly higher among unvaccinated patients compared to partially and fully vaccinated patients (p-value=0.001). Fully vaccinated patients had almost low CT severity score indicating mild form of disease. Conclusion: To the best of authors knowledge, this study is the first to describe the chest CT severity scores of vaccinated individuals in comparison with the unvaccinated COVID-19 infected patients. The disease severity was significantly higher among unvaccinated patients compared to partially and fully vaccinated patients. The present study has provided substantial evidence of vaccine efficacy in reducing the disease severity in COVID-19 infected patients.

A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans.

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as 'acceptable', 'minor disagreement' or 'major disagreement'. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.