Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter

Database
Main subject
Type of study
Journal
Year
Document Type
Year range
1.
Methods ; 205: 200-209, 2022 Jul 08.
Article in English | MEDLINE | ID: covidwho-1926982

##### ABSTRACT

BACKGROUND: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. METHODS: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. RESULTS: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. CONCLUSION: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its ability to segment lesions without the need for manual segmentations.

2.
Crit Care ; 26(1): 199, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1916967

##### ABSTRACT

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

##### Subject(s)
COVID-19 , Pandemics , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Middle Aged , Prospective Studies , Registries
3.
Intensive Care Med Exp ; 10(1): 28, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1910362

##### ABSTRACT

Nitric oxide (NO) is a key molecule in the biology of human life. NO is involved in the physiology of organ viability and in the pathophysiology of organ dysfunction, respectively. In this narrative review, we aimed at elucidating the mechanisms behind the role of NO in the respiratory and cardio-cerebrovascular systems, in the presence of a healthy or dysfunctional endothelium. NO is a key player in maintaining multiorgan viability with adequate organ blood perfusion. We report on its physiological endogenous production and effects in the circulation and within the lungs, as well as the pathophysiological implication of its disturbances related to NO depletion and excess. The review covers from preclinical information about endogenous NO produced by nitric oxide synthase (NOS) to the potential therapeutic role of exogenous NO (inhaled nitric oxide, iNO). Moreover, the importance of NO in several clinical conditions in critically ill patients such as hypoxemia, pulmonary hypertension, hemolysis, cerebrovascular events and ischemia-reperfusion syndrome is evaluated in preclinical and clinical settings. Accordingly, the mechanism behind the beneficial iNO treatment in hypoxemia and pulmonary hypertension is investigated. Furthermore, investigating the pathophysiology of brain injury, cardiopulmonary bypass, and red blood cell and artificial hemoglobin transfusion provides a focus on the potential role of NO as a protective molecule in multiorgan dysfunction. Finally, the preclinical toxicology of iNO and the antimicrobial role of NO-including its recent investigation on its role against the Sars-CoV2 infection during the COVID-19 pandemic-are described.

4.
Encyclopedia ; 1(3):831, 2021.
Article in English | ProQuest Central | ID: covidwho-1834752

##### ABSTRACT

Definitionβ-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties.

5.
Ann Intensive Care ; 12(1): 35, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1785171

##### ABSTRACT

BACKGROUND: External chest-wall compression (ECC) is sometimes used in ARDS patients despite lack of evidence. It is currently unknown whether this practice has any clinical benefit in patients with COVID-19 ARDS (C-ARDS) characterized by a respiratory system compliance (Crs) < 35 mL/cmH2O. OBJECTIVES: To test if an ECC with a 5 L-bag in low-compliance C-ARDS can lead to a reduction in driving pressure (DP) and improve gas exchange, and to understand the underlying mechanisms. METHODS: Eleven patients with low-compliance C-ARDS were enrolled and underwent 4 steps: baseline, ECC for 60 min, ECC discontinuation and PEEP reduction. Respiratory mechanics, gas exchange, hemodynamics and electrical impedance tomography were recorded. Four pigs with acute ARDS were studied with ECC to understand the effect of ECC on pleural pressure gradient using pleural pressure transducers in both non-dependent and dependent lung regions. RESULTS: Five minutes of ECC reduced DP from baseline 14.2 ± 1.3 to 12.3 ± 1.3 cmH2O (P < 0.001), explained by an improved lung compliance. Changes in DP by ECC were strongly correlated with changes in DP obtained with PEEP reduction (R2 = 0.82, P < 0.001). The initial benefit of ECC decreased over time (DP = 13.3 ± 1.5 cmH2O at 60 min, P = 0.03 vs. baseline). Gas exchange and hemodynamics were unaffected by ECC. In four pigs with lung injury, ECC led to a decrease in the pleural pressure gradient at end-inspiration [2.2 (1.1-3) vs. 3.0 (2.2-4.1) cmH2O, P = 0.035]. CONCLUSIONS: In C-ARDS patients with Crs < 35 mL/cmH2O, ECC acutely reduces DP. ECC does not improve oxygenation but it can be used as a simple tool to detect hyperinflation as it improves Crs and reduces Ppl gradient. ECC benefits seem to partially fade over time. ECC produces similar changes compared to PEEP reduction.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311028

##### ABSTRACT

The purpose of this study was to develop a fully-automated segmentation algorithm, robust to various density enhancing lung abnormalities, to facilitate rapid quantitative analysis of computed tomography images. A polymorphic training approach is proposed, in which both specifically labeled left and right lungs of humans with COPD, and nonspecifically labeled lungs of animals with acute lung injury, were incorporated into training a single neural network. The resulting network is intended for predicting left and right lung regions in humans with or without diffuse opacification and consolidation. Performance of the proposed lung segmentation algorithm was extensively evaluated on CT scans of subjects with COPD, confirmed COVID-19, lung cancer, and IPF, despite no labeled training data of the latter three diseases. Lobar segmentations were obtained using the left and right lung segmentation as input to the LobeNet algorithm. Regional lobar analysis was performed using hierarchical clustering to identify radiographic subtypes of COVID-19. The proposed lung segmentation algorithm was quantitatively evaluated using semi-automated and manually-corrected segmentations in 87 COVID-19 CT images, achieving an average symmetric surface distance of $0.495 \pm 0.309$ mm and Dice coefficient of $0.985 \pm 0.011$. Hierarchical clustering identified four radiographical phenotypes of COVID-19 based on lobar fractions of consolidated and poorly aerated tissue. Lower left and lower right lobes were consistently more afflicted with poor aeration and consolidation. However, the most severe cases demonstrated involvement of all lobes. The polymorphic training approach was able to accurately segment COVID-19 cases with diffuse consolidation without requiring COVID-19 cases for training.

7.
Nitric Oxide ; 121: 20-33, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1665319

##### ABSTRACT

Inhaled nitric oxide (iNO) acts as a selective pulmonary vasodilator and it is currently approved by the FDA for the treatment of persistent pulmonary hypertension of the newborn. iNO has been demonstrated to effectively decrease pulmonary artery pressure and improve oxygenation, while decreasing extracorporeal life support use in hypoxic newborns affected by persistent pulmonary hypertension. Also, iNO seems a safe treatment with limited side effects. Despite the promising beneficial effects of NO in the preclinical literature, there is still a lack of high quality evidence for the use of iNO in clinical settings. A variety of clinical applications have been suggested in and out of the critical care environment, aiming to use iNO in respiratory failure and pulmonary hypertension of adults or as a preventative measure of hemolysis-induced vasoconstriction, ischemia/reperfusion injury and as a potential treatment of renal failure associated with cardiopulmonary bypass. In this narrative review we aim to present a comprehensive summary of the potential use of iNO in several clinical conditions with its suggested benefits, including its recent application in the scenario of the COVID-19 pandemic. Randomized controlled trials, meta-analyses, guidelines, observational studies and case-series were reported and the main findings summarized. Furthermore, we will describe the toxicity profile of NO and discuss an innovative proposed strategy to produce iNO. Overall, iNO exhibits a wide range of potential clinical benefits, that certainly warrants further efforts with randomized clinical trials to determine specific therapeutic roles of iNO.

##### Subject(s)
Critical Illness , Hypertension, Pulmonary/drug therapy , Infant, Newborn, Diseases/drug therapy , Nitric Oxide/therapeutic use , Vasodilator Agents/therapeutic use , Adult , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Humans , Hypertension, Pulmonary/etiology , Infant, Newborn , Infant, Newborn, Diseases/etiology , Nitric Oxide/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Vasodilator Agents/pharmacology
8.
Crit Care ; 26(1): 8, 2022 01 06.
Article in English | MEDLINE | ID: covidwho-1590188

##### ABSTRACT

BACKGROUND: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. METHODS: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to "conventional" ECMO management (Supine group) in patients with severe ARDS. RESULTS: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42-1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). CONCLUSIONS: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

##### Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Data Analysis , Humans , Patient Positioning , Prone Position , Prospective Studies , Respiratory Distress Syndrome/therapy , Retrospective Studies
9.
Chest ; 160(4): 1335-1339, 2021 10.
Article in English | MEDLINE | ID: covidwho-1487649
10.
Minerva Anestesiol ; 87(12): 1383-1385, 2021 12.
Article in English | MEDLINE | ID: covidwho-1311487
11.
Crit Care ; 25(1): 175, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243815

##### ABSTRACT

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

##### Subject(s)
COVID-19/therapy , Critical Illness/therapy , Respiratory Therapy/methods , Respiratory Therapy/statistics & numerical data , Aged , COVID-19/mortality , Critical Illness/mortality , Disease Progression , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Registries , Retrospective Studies , Time Factors , Treatment Outcome
12.
Anesthesiol Clin ; 39(2): 265-284, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1240164

##### ABSTRACT

Italy was the first western country facing an outbreak of coronavirus disease 2019 (COVID-19). The first Italian patient diagnosed with COVID-19 was admitted, on Feb. 20, 2020, to the intensive care unit (ICU) in Codogno (Lodi, Lombardy, Italy), and the number of reported positive cases increased to 36 in the next 24 hours, and then exponentially for 18 days. This triggered a response that resulted in a massive surge in ICU bed capacity. The COVID19 Lombardy Network organized a structured logistic response and provided scientific evidence to highlight information on COVID-19 associated respiratory failure.

##### Subject(s)
COVID-19 , Critical Care/organization & administration , Pandemics , Airway Management , Humans , Intensive Care Units , Italy
13.
Sci Rep ; 11(1): 1455, 2021 01 14.
Article in English | MEDLINE | ID: covidwho-1065938

##### ABSTRACT

The purpose of this study was to develop a fully-automated segmentation algorithm, robust to various density enhancing lung abnormalities, to facilitate rapid quantitative analysis of computed tomography images. A polymorphic training approach is proposed, in which both specifically labeled left and right lungs of humans with COPD, and nonspecifically labeled lungs of animals with acute lung injury, were incorporated into training a single neural network. The resulting network is intended for predicting left and right lung regions in humans with or without diffuse opacification and consolidation. Performance of the proposed lung segmentation algorithm was extensively evaluated on CT scans of subjects with COPD, confirmed COVID-19, lung cancer, and IPF, despite no labeled training data of the latter three diseases. Lobar segmentations were obtained using the left and right lung segmentation as input to the LobeNet algorithm. Regional lobar analysis was performed using hierarchical clustering to identify radiographic subtypes of COVID-19. The proposed lung segmentation algorithm was quantitatively evaluated using semi-automated and manually-corrected segmentations in 87 COVID-19 CT images, achieving an average symmetric surface distance of [Formula: see text] mm and Dice coefficient of [Formula: see text]. Hierarchical clustering identified four radiographical phenotypes of COVID-19 based on lobar fractions of consolidated and poorly aerated tissue. Lower left and lower right lobes were consistently more afflicted with poor aeration and consolidation. However, the most severe cases demonstrated involvement of all lobes. The polymorphic training approach was able to accurately segment COVID-19 cases with diffuse consolidation without requiring COVID-19 cases for training.

##### Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Neural Networks, Computer , Pulmonary Fibrosis/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed , Female , Humans , Male
14.
Ann Am Thorac Soc ; 18(6): 1020-1026, 2021 06.
Article in English | MEDLINE | ID: covidwho-1006326

##### ABSTRACT

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited.Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy.Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio <150 mm Hg. Higher C-reactive protein and lower PaO2/FiO2 and platelet counts were independently associated with increased risk of NIV failure.Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).

##### Subject(s)
COVID-19/therapy , Continuous Positive Airway Pressure/methods , Hospital Mortality , Hypoxia/therapy , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/methods , Patients' Rooms , Respiratory Insufficiency/therapy , Aged , Cannula , Female , Humans , Intensive Care Units , Italy , Male , Middle Aged , Oxygen Inhalation Therapy , Prospective Studies , SARS-CoV-2 , Treatment Failure
15.
Intensive Care Med ; 46(12): 2265-2283, 2020 12.
Article in English | MEDLINE | ID: covidwho-639094

##### ABSTRACT

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.

##### Subject(s)
COVID-19/drug therapy , Drug Therapy/trends , Respiratory Distress Syndrome/drug therapy , Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Citrulline/therapeutic use , Glycoproteins/therapeutic use , Humans , Mesenchymal Stem Cells , Pandemics , Peptides, Cyclic/therapeutic use , Pyridones/therapeutic use , Pyrimidines/therapeutic use , Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors , Receptors, Tumor Necrosis Factor, Type I/therapeutic use , Steroids/therapeutic use , Trypsin Inhibitors/therapeutic use
16.
Sci Total Environ ; 732: 139330, 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-291564

##### ABSTRACT

Coronavirus pneumonia is accompanied by rapid virus replication, where a large number of inflammatory cell infiltration and cytokine storm may lead to acute lung injury, acute respiratory distress syndrome (ARDS) and death. The uncontrolled release of pro-inflammatory cytokines, including interleukin (IL)-1ß and IL-6, is associated with ARDS. This constituted the first study to report on the variability in physicochemical properties of ß-glucans extracts from the same edible mushroom Lentinus edodes on the reduction of these pro-inflammatory cytokines and oxidative stress. Specifically, the impact on the immunomodulatory and cytoprotective properties of our novel in 'house' (IH-Lentinan, IHL) and a commercial (Carbosynth-Lentinan, CL) Lentinan extract were investigated using in vitro models of lung injury and macrophage phagocytosis. CL comprised higher amounts of α-glucans and correspondingly less ß-glucans. The two lentinan extracts demonstrated varying immunomodulatory activities. Both Lentinan extracts reduced cytokine-induced NF-κB activation in human alveolar epithelial A549 cells, with the IHL extract proving more effective at lower doses. In contrast, in activated THP-1 derived macrophages, the CL extract more effectively attenuated pro-inflammatory cytokine production (TNF-α, IL-8, IL-2, IL-6, IL-22) as well as TGF-ß and IL-10. The CL extract attenuated oxidative stress-induced early apoptosis, while the IHL extract attenuated late apoptosis. Our findings demonstrate significant physicochemical differences between Lentinan extracts, which produce differential in vitro immunomodulatory and pulmonary cytoprotective effects that may also have positive relevance to candidate COVID-19 therapeutics targeting cytokine storm.

##### Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Shiitake Mushrooms , COVID-19 , Humans , Immunotherapy , SARS-CoV-2 , beta-Glucans