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1.
Khirurgiia (Mosk) ; (4): 5-10, 2022.
Article in Russian | MEDLINE | ID: covidwho-1818835

ABSTRACT

OBJECTIVE: To analyze postoperative outcomes and perioperative management of patients with post-intensive care tracheal stenosis and previous COVID-19 pneumonia. MATERIAL AND METHODS: There were 8 patients with post-intensive care tracheal stenosis and previous COVID-19 pneumonia aged 34-61 years between January 2021 and April 2021. Lung damage CT-3 was observed in 2 (25%) patients, CT-4 - in 5 (62.5%) patients. In one case, COVID-19 pneumonia with lung damage CT-2 joined to acute cerebrovascular accident. Post-tracheostomy stenosis was detected in 7 (87.5%) cases, post-intubation stenosis - in 1 patient. Duration of invasive mechanical ventilation ranged from 5 to 130 days. In 75% of cases, tracheal stenosis was localized in the larynx and cervical trachea. Two patients admitted with tracheostomy. In one case, an extended tracheal stenosis was combined with atresia of infraglottic part of the larynx. One patient had tracheal stenosis combined with tracheoesophageal fistula (TEF). Length of tracheal stenosis was 15-45 mm. Tracheomalacia was observed in 4 (50%) patients. All patients had severe concomitant diseases. RESULTS: To restore airway patency, we used circular tracheal resection with anastomosis, laryngotracheoplasty and endoscopic methods. Tracheal resection combined with TEF required circular tracheal resection with disconnection of fistula. Adequate breathing through the natural airways was restored in all patients. There was no postoperative mortality. Three patients with baseline tracheal stenosis had favorable postoperative outcomes after circular tracheal resection. Four patients are at the final stage of treatment after laryngotracheoplasty and tracheal stenting. CONCLUSION: Patients after invasive mechanical ventilation for COVID-19 pneumonia are at high risk of cicatricial tracheal stenosis and require follow-up. Circular tracheal resection ensures early rehabilitation and favorable functional results. Laryngotracheoplasty is preferred if circular tracheal resection is impossible. This procedure ensures adequate debridement of tracheobronchial tree and respiratory support. Endoscopic measures are an alternative for open surgery, especially for intrathoracic tracheal stenosis and intractable tracheobronchitis.


Subject(s)
COVID-19 , Tracheal Stenosis , Tracheoesophageal Fistula , Constriction, Pathologic/surgery , Critical Care , Humans , Trachea/surgery , Tracheal Stenosis/diagnosis , Tracheal Stenosis/etiology , Tracheal Stenosis/surgery
2.
Rev. colomb. cir ; 37(2): 305-307, 20220316. fig
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-1786587

ABSTRACT

Se han descrito diversas técnicas para el tratamiento del enfisema subcutáneo y del neumomediastino. Algunos pacientes con pequeñas perforaciones traqueales pueden ser manejados de forma expectante, salvo que requieran ventilación mecánica. Se presentan las imágenes de un paciente con enfisema subcutáneo y neumomediastino no candidato a cirugía y quien fue tratado exitosamente con terapia de presión negativa.


Different techniques have been described for the treatment of subcutaneous emphysema and pneumomediatinum. Some patients with small tracheal perforations can be managed expectantly, unless they require mechanical ventilation. Images of a patient with subcutaneous emphysema and pneumomediastinum not a candidate for surgery and who was successfully treated with negative pressure therapy are presented.


Subject(s)
Humans , Subcutaneous Emphysema , COVID-19 , Trachea , Ventilators, Negative-Pressure , Mediastinal Emphysema
3.
Sci Rep ; 12(1): 4599, 2022 03 29.
Article in English | MEDLINE | ID: covidwho-1768844

ABSTRACT

Dehydration of the upper airways increases risks of respiratory diseases from COVID-19 to asthma and COPD. We find in human volunteer studies involving 464 human subjects in Germany, the US, and India that respiratory droplet generation increases by up to 4 orders of magnitude in dehydration-associated states of advanced age (n = 357), elevated BMI-age (n = 148), strenuous exercise (n = 20) and SARS-CoV-2 infection (n = 87), and falls with hydration of the nose, larynx and trachea by calcium-rich hypertonic salts. We also find in a protocol of exercise-induced airway dehydration that hydration of the airways by calcium-rich salts increases oxygenation relative to a non-treatment control (P < 0.05). In a random control study of COVID-19 positive subjects (n = 40), thrice-a-day delivery of the calcium-rich hypertonic salts (active) suppressed respiratory droplet generation by 51% ± 11% and increased oxygen saturation over three days of treatment by 48.08% ± 9.61% (P < 0.001), while no changes were observed in the nasal-saline control group. Self-reported symptoms significantly declined in the active group and did not decline in the control group. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of respiratory diseases such as COVID-19.


Subject(s)
COVID-19 , Larynx , Exercise , Humans , SARS-CoV-2 , Trachea
4.
Virus Genes ; 58(3): 203-213, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1766911

ABSTRACT

Infectious bronchitis virus (IBV) and avian influenza virus (AIV) are two major respiratory infections in chickens. The coinfection of these viruses can cause significant financial losses and severe complications in the poultry industry across the world. To examine transcriptome profile changes during the early stages of infection, differential transcriptional profiles in tracheal tissue of three infected groups (i.e., IBV, AIV, and coinfected) were compared with the control group. Specific-pathogen-free chickens were challenged with Iranian variant-2-like IBV (IS/1494), UT-Barin isolates of H9N2 (A/chicken/Mashhad/UT-Barin/2017), and IBV-AIV coinfection; then, RNA was extracted from tracheal tissue. The Illumina RNA-sequencing (RNA-seq) technique was employed to investigate changes in the Transcriptome. Up- and downregulated differentially expressed genes (DEGs) were detected in the trachea transcriptome of all groups. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology databases were examined to identify possible relationships between DEGs. In the experimental groups, upregulated genes were higher compared to downregulated genes. A more severe immune response was observed in the coinfected group; further, cytokine-cytokine receptor interaction, RIG-I-like receptor signaling, Toll-like receptor signaling, NOD-like receptor signaling, Janus kinase/signal transducer, and activator of transcription, and apoptotic pathways were important upregulated genes in this group. The findings of this paper may give a better understanding of transcriptome changes in the trachea during the early stages of infection with these viruses.


Subject(s)
Bronchitis , Coinfection , Coronavirus Infections , Infectious bronchitis virus , Influenza A Virus, H9N2 Subtype , Influenza in Birds , Poultry Diseases , Animals , Bronchitis/genetics , Bronchitis/veterinary , Chickens , Gene Expression Profiling , Infectious bronchitis virus/genetics , Influenza A Virus, H9N2 Subtype/genetics , Influenza in Birds/genetics , Iran , Poultry Diseases/genetics , RNA , Trachea , Transcriptome/genetics
6.
Viruses ; 14(3)2022 03 13.
Article in English | MEDLINE | ID: covidwho-1742725

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Delta variant has evolved to become the dominant SARS-CoV-2 lineage with multiple sub-lineages and there are also reports of re-infections caused by this variant. We studied the disease characteristics induced by the Delta AY.1 variant and compared it with the Delta and B.1 variants in Syrian hamsters. We also assessed the potential of re-infection by these variants in Coronavirus disease 2019 recovered hamsters 3 months after initial infection. The variants produced disease characterized by high viral load in the respiratory tract and interstitial pneumonia. The Delta AY.1 variant produced mild disease in the hamster model and did not show any evidence of neutralization resistance due to the presence of the K417N mutation, as speculated. Re-infection with a high virus dose of the Delta and B.1 variants 3 months after B.1 variant infection resulted in reduced virus shedding, disease severity and increased neutralizing antibody levels in the re-infected hamsters. The reduction in viral load and lung disease after re-infection with the Delta AY.1 variant was not marked. Upper respiratory tract viral RNA loads remained similar after re-infection in all the groups. The present findings show that prior infection could not produce sterilizing immunity but that it can broaden the neutralizing response and reduce disease severity in case of reinfection.


Subject(s)
COVID-19 , Reinfection , Animals , Cricetinae , Mesocricetus , SARS-CoV-2/genetics , Severity of Illness Index , Trachea
7.
Biomed Pharmacother ; 148: 112753, 2022 04.
Article in English | MEDLINE | ID: covidwho-1707727

ABSTRACT

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.


Subject(s)
Acetylcysteine/pharmacology , Bromelains/pharmacology , COVID-19/pathology , Chemokines/drug effects , Cytokines/drug effects , Sputum/cytology , Acetylcysteine/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Bromelains/administration & dosage , Cytokine Release Syndrome/pathology , Dose-Response Relationship, Drug , Down-Regulation , Drug Combinations , Expectorants/pharmacology , Female , Humans , Inflammation Mediators/metabolism , Male , Middle Aged , Respiration, Artificial , Rheology , SARS-CoV-2 , Trachea/pathology , Young Adult
8.
J Med Virol ; 94(6): 2833-2836, 2022 06.
Article in English | MEDLINE | ID: covidwho-1669584

ABSTRACT

COVID-19 vaccines provide high levels of protection against severe disease and hospitalization due to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Vaccination may be less effective in preventing shedding of infectious viruses from otherwise immune patients. In this study, we describe breakthrough infections and shedding of infectious viruses in convalescent hamsters without significant replication in the lower respiratory tract following reinfection by Alpha and Delta variants despite high levels of circulating antibodies in sera. Using convalescent hamsters with long-term immunity (up to 1 year) following infection by ancestral SARS-CoV-2, we can model aspects of recurring COVID-19 in the context of preexisting immunity.


Subject(s)
COVID-19 , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Cricetinae , Humans , Mesocricetus , SARS-CoV-2 , Trachea
10.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1625612

ABSTRACT

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl- currents and intracellular Ca2+ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca2+ activated Cl- channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca2+ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.


Subject(s)
Niclosamide/administration & dosage , Pneumonia/drug therapy , Respiratory System/drug effects , Animals , Asthma/drug therapy , Asthma/metabolism , Asthma/pathology , COVID-19/complications , COVID-19/drug therapy , Cells, Cultured , Disease Models, Animal , Drug Carriers/chemistry , Drug Compounding , Humans , Hydrogels/chemistry , Instillation, Drug , Mice , Microspheres , Mucus/drug effects , Mucus/metabolism , Nanospheres/administration & dosage , Nanospheres/chemistry , Niclosamide/chemistry , Niclosamide/pharmacokinetics , Pneumonia/pathology , Polyethylene Glycols/chemistry , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory System/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Trachea
11.
Sensors (Basel) ; 22(2)2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1625110

ABSTRACT

The COVID-19 outbreak has increased the incidence of tracheal lesions in patients who underwent invasive mechanical ventilation. We measured the pressure exerted by the cuff on the walls of a test bench mimicking the laryngotracheal tract. The test bench was designed to acquire the pressure exerted by endotracheal tube cuffs inflated inside an artificial model of a human trachea. The experimental protocol consisted of measuring pressure values before and after applying a maneuver on two types of endotracheal tubes placed in two mock-ups resembling two different sized tracheal tracts. Increasing pressure values were used to inflate the cuff and the pressures were recorded in two different body positions. The recorded pressure increased proportionally to the input pressure. Moreover, the pressure values measured when using the non-armored (NA) tube were usually higher than those recorded when using the armored (A) tube. A periodic check of the cuff pressure upon changing the body position and/or when performing maneuvers on the tube appears to be necessary to prevent a pressure increase on the tracheal wall. In addition, in our model, the cuff of the A tube gave a more stable output pressure on the tracheal wall than that of the NA tube.


Subject(s)
COVID-19 , Trachea , Humans , Intensive Care Units , Intubation, Intratracheal , SARS-CoV-2
12.
Nature ; 602(7896): 321-327, 2022 02.
Article in English | MEDLINE | ID: covidwho-1585831

ABSTRACT

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.


Subject(s)
COVID-19/blood , COVID-19/immunology , Dendritic Cells/immunology , Interferons/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Bronchi/immunology , Bronchi/virology , COVID-19/pathology , Chicago , Cohort Studies , Disease Progression , Epithelial Cells/cytology , Epithelial Cells/immunology , Epithelial Cells/virology , Female , Humans , Immunity, Innate , London , Male , Nasal Mucosa/immunology , Nasal Mucosa/virology , SARS-CoV-2/growth & development , Single-Cell Analysis , Trachea/virology , Young Adult
13.
J Infect Dis ; 224(12): 2020-2024, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1575544

ABSTRACT

BACKGROUND: The upper respiratory tract (URT) is the primary entry site for severe acute respiratory syndrome 2 (SARS-CoV-2) and other respiratory viruses, but its involvement in viral amplification and pathogenesis remains incompletely understood. METHODS: In this study, we investigated primary nasal epithelial cultures, as well as vital explanted tissues, to scrutinize the tropism of wild-type SARS-CoV-2 and the recently emerged B.1.1.7 variant. RESULTS: Our analyses revealed a widespread replication competence of SARS-CoV-2 in polarized nasal epithelium as well as in the examined URT and salivary gland tissues, which was also shared by the B.1.1.7 virus. CONCLUSIONS: In our analyses, we highlighted the active role of these anatomic sites in coronavirus disease 2019.


Subject(s)
COVID-19/virology , Respiratory System/virology , Viral Tropism , Virus Replication , Humans , Respiratory Tract Infections , SARS-CoV-2 , Trachea
16.
Immun Inflamm Dis ; 9(4): 1716-1723, 2021 12.
Article in English | MEDLINE | ID: covidwho-1513802

ABSTRACT

BACKGROUND: Normally functioning airway cilia is essential for efficient mucociliary clearance to protect the airway from various insults. Impaired clearance may lead to increased risk of infections and progressive lung damage. Significant morbidity in the immediate post lung transplantation period is associated with airway infection, which we hypothesize may be caused by impaired cilia function. METHODS: Airway cilia beating pattern (CBP) and frequency (CBF) were studied on brushing samples taken from above and below the transplant anastomosis of adult lung transplant recipients (n = 20) during routine bronchoscopies at 6, 12, and 26 weeks posttransplant. Bronchoaveolar Lavage (BAL) samples were also collected at each time points. RESULTS: At 6 weeks posttransplant (n = 16), CBP from the donated lung showed reduced beating amplitude with the overall CBF 2.28 Hz slower than the patients' native upper airway cilia (median ± SIQR: 5.36 ± 0.93 Hz vs. 7.64 ± 0.92 Hz, p value < .001). At 12 weeks (n = 16), donor lungs CBP showed recovery with the difference in CBF reduced to 0.74 Hz (6.36 ± 1.46 Hz vs. 7.10 ± 0.86 Hz, p value < .05). Impaired cilia function was not associated with positive BAL cultures. CONCLUSION: Reduced cilia function is evident in the first 12 weeks post lung transplant, with both CBP and CBF returning to levels of function indistinguishable to the patients' upper airway cilia beyond this time.


Subject(s)
Cilia , Lung Transplantation , Adult , Humans , Lung , Lung Transplantation/adverse effects , Mucociliary Clearance , Trachea
17.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(10): 597-601, 2021 12.
Article in English | MEDLINE | ID: covidwho-1510237

ABSTRACT

Iatrogenic tracheal rupture (ITR) is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of ITR depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-Cov-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Iatrogenic Disease , Pandemics , Respiratory Distress Syndrome/etiology , Rupture , SARS-CoV-2 , Trachea/diagnostic imaging
18.
J Photochem Photobiol B ; 226: 112357, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1510060

ABSTRACT

Mitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E (CoV-229E), and results in increased intracellular levels of MAVS. In this study, we explored the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (e.g. via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 min and in unexposed controls at 30-40% and at 100% confluency, and in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. MAVS was also assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. Our results showed that UVA increases the expression of MAVS protein. Further, cells in a confluent monolayer exposed to UVA conferred an elevation in MAVS in cells adjacent to the exposed section, and also in cells in the most distant sections which were not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to confluent cells not exposed to UVA, likely via cell-cell signaling.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/radiation effects , Ultraviolet Rays , Adaptor Proteins, Signal Transducing/immunology , COVID-19/immunology , COVID-19/radiotherapy , COVID-19/virology , Cell Communication/immunology , Cell Communication/radiation effects , Cells, Cultured , Epithelial Cells/immunology , Epithelial Cells/radiation effects , Host Microbial Interactions/immunology , Host Microbial Interactions/radiation effects , Humans , Immunity, Innate/radiation effects , Photobiology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction/immunology , Signal Transduction/radiation effects , Trachea/cytology , Ultraviolet Therapy
19.
Molecules ; 26(21)2021 Nov 06.
Article in English | MEDLINE | ID: covidwho-1502470

ABSTRACT

The normal function of the airway epithelium is vital for the host's well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction.


Subject(s)
Respiratory Mucosa/metabolism , Tissue Engineering/methods , Trachea/transplantation , Cell Differentiation , Cell Proliferation , Epithelial Cells/metabolism , Epithelium/metabolism , Feasibility Studies , Humans , Ki-67 Antigen/analysis , Ki-67 Antigen/genetics , Mucin 5AC/analysis , Mucin 5AC/genetics , Mucous Membrane/metabolism , Primary Cell Culture/methods , Respiratory Mucosa/physiology , Trachea/metabolism , Trachea/physiology
20.
Sci Rep ; 11(1): 20595, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475487

ABSTRACT

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Light , SARS-CoV-2 , Trachea/radiation effects , Virus Replication/radiation effects , Adult , Animals , Antiviral Agents/pharmacology , Bronchi , Calibration , Cell-Free System , Chlorocebus aethiops , Epithelium/pathology , Female , Humans , Respiratory Mucosa/radiation effects , Trachea/virology , Vero Cells
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