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1.
Acta Pharm Sin B ; 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-2031130

ABSTRACT

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 µmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 µmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

2.
Journal of Trace Elements in Medicine and Biology ; : 127075, 2022.
Article in English | ScienceDirect | ID: covidwho-2031499

ABSTRACT

Background Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. Materials and methods A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. Results In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29µg/dL, 132.53µg/dL, 106.3mg/dL, 17.74% and 702.9ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53µg/dL, 391.88µg/dL, 313.51mg/dL, 12.81% and 13.52ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat% and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74%, 63% and 61% respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p<0.01), iron-TIBC (p<0.001) and transferrin-ferritin (P<0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2%. The cutoff point according to Youden’s J index is characterized with a sensitivity of 98% and a specificity of 96.8%, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. Conclusion Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

3.
Journal of Drug Delivery Science and Technology ; : 103805, 2022.
Article in English | ScienceDirect | ID: covidwho-2031441

ABSTRACT

Cannabidiol (CBD) was formulated as a metered dose inhaler (CBD-MDI) and evaluated in vitro for its efficacy as an inhaled dosage form against inflammation caused by the SARS-CoV-2 virus, lipopolysaccharide (LPS) from Escherichia coli, silica particles, nicotine, and coal tar. A CBD-MDI formulation was prepared with 50 mg of CBD in 10 mL for a CBD dose of 250 μg/puff. The formulation ingredients included CBD, absolute ethanol as a cosolvent, and HFA-134a as the propellant. High aerosol performance of CBD-MDI was obtained with mass median aerodynamic diameter of 1.25 ± 0.01 μm, geometric standard deviation of 1.75 ± 0.00, emitted dose of 244.7 ± 2.1 μg, and fine particle dose of 122.0 ± 1.6 μg). The cytotoxicity and anti-inflammatory effectiveness of CBD-MDI were performed in alveolar macrophage (NR8383) and co-culture of alveolar macrophage (NR8383) and human lung adenocarcinoma (A549) cell line. CBD delivered from an MDI was safe on respiratory cells and did not trigger an immune response in alveolar macrophages. CBD-MDI effectively reduced the generation of cytokines in immune cells treated with viral antigen S-RBD, bacterial antigen LPS, silica particles, and coal tar. The efficacy of CBD-MDI was comparable to budesonide. Furthermore, the findings demonstrated that the use of CBD-MDI was more effective in treatment rather than prevention when inflammation was induced by either a viral or bacterial stimulant.

4.
J Allergy Clin Immunol ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031406

ABSTRACT

BACKGROUND: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after SARS-CoV-2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis, therefore establishing clinical and laboratory biomarkers that predict complications is urgently needed. OBJECTIVE: To characterize the immune response and clinical features of patients with acute MIS-C and determine biomarkers of disease in a cohort of 42 Latin American patients. METHODS: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and SARS-CoV-2-specific humoral and cellular response was performed using flow cytometry, ELISPOT, ELISA and neutralizing antibody assays. RESULTS: MIS-C is characterized by robust T cell activation and cytokine storm. We uncovered that while CXCL9, IL-10, CXCL8, CXCL10, IL-6 and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated to Kawasaki-like MIS-C. Interestingly, MIS-C patients show an NK cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. SARS-CoV2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients suggesting sustained immunity. CONCLUSION: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement. CLINICAL IMPLICATIONS STATEMENT: MIS-C is distinguished by cytokine storm and decreased NK cell degranulation that is persistent after 6 months. Distinct biomarkers were identified for severe and mild forms of disease.

5.
Journal of the American Academy of Dermatology ; 87(3):AB216, 2022.
Article in English | EMBASE | ID: covidwho-2031400

ABSTRACT

Preaging is an emerging concept in China whereby young women are looking for skin aging solutions. Among the intrinsic and extrinsic causes of skin aging, mental stress was highlighted as a possible cause of preaging in young women. The COVID-19 pandemic has further impacted the mental well-being of the younger generation, with 44% of Asian women aged 18 to 34 under poor mental well-being based on WHO-5. While 76.5% of dermatologists agreed that there is a strong connection between stress and skin aging, there is limited evidence on the pathophysiology. The aim of this research is to explore how clinicians understand the impact of stress and the biologic pathways connecting stress and skin aging. A quantitative survey with 60 dermatologists and 60 psychologists from China and Japan was conducted to assess the link between stress and skin aging. Overall, 69.2% of both health care professionals agree that psychological stress has a significant link to skin aging. Three meta-themes were perceived by clinician as possible pathways connecting psychological stress and skin aging, including stress hormone, inflammation, and overactive immune system. While all health care professionals have heard of inflammaging, only 52% are very familiar with the concept. Both groups agree that unresolved acute inflammatory response can accelerate skin aging. Surprisingly, a significant difference was observed in that psychologists believe more strongly than dermatologists that chronic low-grade inflammation accelerates skin aging. This study highlights the need for further fundamental research, which could help clinicians provide appropriate recommendations for patients under psychological stress.

6.
Journal of the American Academy of Dermatology ; 87(3):AB27, 2022.
Article in English | EMBASE | ID: covidwho-2031371

ABSTRACT

Introduction: Telogen effluvium (TE) is characterized by diffuse hair shedding 2-3 months after a stressor, and factors such as hypoxia, inflammation (interleukin 6), medications and need for mechanical ventilation may play a role in the development and severity of TE caused by COVID-19. Aims: Evaluate the benefit of the hair care routine using products containing active ingredients to reduce the microinflammation of the scalp and increase the resistance of the hair strand to treat subjects with TE caused by COVID-19. Case presentation: After 60 days of the hospitalization due to COVID-19 infection, a 58-year-old woman showed a typical diagnostic of TE associated to post–COVID-19 infection, presenting positive results to traction test, trichoscopy, and trichogram. During 30 days, she used: 1) Product A: shampoo containing Aminexil, niacinamide, pyridoxine and panthenol;2) Product B: conditionate containing SP94 (glucose + linoleic acid);and 3) Product C: treatment ampoules containing creatine, panthenol, and ceramide R. The products A plus B were used once time for daily and the product C was used 3 times a week. Results: After the treatment, the subject presented an improvement of 100% of the hair loss, with negative results to traction test, trichoscopy, and trichogram analysis. The subject reported a high satisfaction with the treatment (ratio 10/10). Discussion: The hair care routine using the products A, B, and C could improve the TE caused by COVID-19, maybe by reduction inflammatory process in the scalp. Clinical studies in the high scale must be conducted to proof this hypothesis.

7.
Colloids and Surfaces B: Biointerfaces ; 219, 2022.
Article in English | EMBASE | ID: covidwho-2031218

ABSTRACT

Cell membrane cloaking is an important biomimetic approach for improving drug residence time in the body due to its distinctive concealment ability, making it highly biocompatible and efficient for targeted drug delivery. Leukocytes are considered a fundamental part of the immune system. Leukocyte membrane cloaked nanoparticles offer site-specificity and can escape the opsonization process besides enhanced systemic circulation time. This review emphasizes the anatomical and physiological features of different leukocytes in addition to the preparation and characterization of leukocyte membrane cloaked nanoparticles. It also covers the recent advancements of this biointerfacing platform in cancer therapy, inflammatory disorders, multifunctional targeted therapy and hybrid membrane-coated nanoparticles. However, leukocytes are complex, nucleated cell structures and isolating their membranes poses a greater difficulty. Leukocyte membrane cloaking is an upcoming strategy in the infancy stage;nevertheless, there is immense scope to explore this biomimetic delivery system in terms of clinical transition, particularly for inflammatory diseases and cancer.

8.
Biologicals ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031158

ABSTRACT

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant lower CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.

9.
Alergia Astma Immunologia ; 27(2):68-74, 2022.
Article in Polish | EMBASE | ID: covidwho-2030741

ABSTRACT

The Coronaviridae family includes the seven known human coronavi-ruses (HCoV) that cause mild to moderate respiratory infections (HCo-V-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) as well as severe illness and death (MERS-CoV, SARS-CoV, SARS-CoV-2). Severe infections in-duce inflammatory responses that are often intensified by host ada-ptive immune pathways. Proinflammatory responses are triggered by CoV entry mediated by host cell surface receptors. Interestingly, four of the seven strains use cell surface metallopeptidases as receptors. The entry receptors for specific coronaviruses are: aminopeptidase N (AP-N), dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme 2 (ACE2) for HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV2, respectively. In addition, these receptors perform many physiological functions, including the regulation of the circulatory and immune sys-tems. Coronavirus receptors are also highly expressed in human tissues and organs (intestines, kidneys, heart, lungs). Additionally, some cy-tokines, chemokines, and other proteins and immune cells influence the modulation of the expression of coronavirus receptors. This review presents the biological role of receptor proteins in the regulation of human physiological systems, the impact of the immune response on susceptibility to coronavirus infections, and the potential effects of glucocorticosteroids (GCS) and specific allergen immunotherapy (AIT) used in the treatment of asthma and allergy on the suscpetibility to coronaviral infections.

10.
Signal Transduction and Targeted Therapy ; 7(1):318, 2022.
Article in English | MEDLINE | ID: covidwho-2028663

ABSTRACT

Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

11.
Stem Cells and COVID-19 ; : 47-57, 2022.
Article in English | Scopus | ID: covidwho-2027791

ABSTRACT

Coronavirus disease 2019 (COVID‐19) is an acute respiratory viral infection caused by SARS-CoV-2, an RNA virus. The first cluster of cases of COVID‐19 was reported from Wuhan, Hubei Province in China in December 2019. Soon after, the virus spread all over the world with 207 M confirmed cases, including 4.3 M deaths as of August 2021. Subsequently, the World Health Organization (WHO) declared the situation a public health emergency of international concern in January 2020 and later declared as a global pandemic threat. COVID‐19 mainly causes damage to the lung as well as other organs and systems such as the heart, the immune system, the nervous system, etc., and thus considered as a multisystem infection. Initial investigations provide insights about the pathogenesis of COVID‐19 and the role of ACE2 receptor has been elucidated. However, there is no complete treatment strategies proposed other than supportive care based on symptoms and severity. Though intense efforts are going on to vaccinate billions of people and at the time of writing 4462.8M vaccine doses have been administered, the pandemic continues spreading at a very fast rate. This chapter discusses the impact of COVID-19 in multisystem inflammation and multiorgan failure. Understanding the molecular and immunological aspects of this disease and diverse susceptibility in different patients would help to design better treatment methods in advance. COVID-19 is characterized by remarkable changes in the histology of multiple organs with high inflammation and necrosis. Along with that, the high imbalance in the immune system with abnormal secretion of proinflammatory cytokines and significant reduction in the circulating lymphocytes increases disease severity and organ damage. Addressing these scenarios carefully would help to discover blood markers or other analysis to predict the possible severity and chances of organ dysfunction in advance and design effective treatment. © 2022 Elsevier Inc. All rights reserved.

12.
Case Reports in Dermatology ; 14(2):203-209, 2022.
Article in English | ProQuest Central | ID: covidwho-2027180

ABSTRACT

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report.

13.
Case Reports in Ophthalmology ; 13(2):350-354, 2022.
Article in English | ProQuest Central | ID: covidwho-2027103

ABSTRACT

Plants of the Araceae family exude a sap containing calcium oxalate, a toxic substance that causes dermatitis. However, ocular injury due to exposure to Araceae sap has rarely been reported. Herein, we present a case of severe pseudomembranous conjunctivitis following exposure to Arisaema ringens, an Araceae species and popular houseplant in Japan. A 67-year-old man presented with pain in his right eye after exposure to the sap of A. ringens. At presentation, the best corrected visual acuity and intraocular pressure in the right eye were 20/800 and 15 mm Hg. Slit-lamp examination showed strong hyperemia, conjunctival chemosis, and corneal edema with many pseudomembranes, and fluorescein staining revealed corneal epithelial defects in the central area of the cornea. We washed the ocular surface with saline and initiated treatment with topical instillations of 1.5% levofloxacin and 0.1% betamethasone, combined with ofloxacin eye ointment. After repeatedly removing the pseudomembranes and increasing the frequency of the topical instillations, pseudomembranous conjunctivitis and corneal erosion gradually improved. One week following the injury, the corneal epithelial defects were no longer detectable, and the patient’s best corrected visual acuity recovered to 20/25. It is important for ophthalmologists and primary care physicians to be aware of the ocular toxicity of A. ringens and should counsel their patients accordingly. Moreover, preventative measures, such as the use of protective eyewear, should be taken when cutting this houseplant.

14.
Biomedicine-Taiwan ; 12(3):56-71, 2022.
Article in English | Web of Science | ID: covidwho-2026734

ABSTRACT

COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and is widely used for COVID-19 patients in Taiwan and more than 50 nations. This study is to investigate in silico target fishing for the components of NRICM101 and to explore whether NRICM101 inhibits cytokines-induced normal human lung cell injury in vitro. Our results showed that network prediction of NRICM101 by a high throughput target screening platform showed that NRICM101 has multiple functions that may affect cytokine regulation to prevent human lung cell injury. In addition, NRICM101 revealed protective effects against TNF-alpha/IL-1 beta-induced normal human lung HEL 299 cell injury through JNK and p38MAPK kinase signaling. Next-generation sequencing (NGS) analysis of NRICM101 on TNF-alpha/IL-1 beta-injured HEL 299 cells indicated that inflammatory pathway, cell movement of macrophages, cellular infiltration by macrophages, and Th1/Th2 immuno-regulation pathways were included. Thus, NRICM101 is a therapeutic agent, and it can improve COVID-19 syndrome to confer beneficial effects through multiple targeting and multiple mechanisms.

15.
Anaesthesia, Pain & Intensive Care ; 26(4):574-575, 2022.
Article in English | Academic Search Complete | ID: covidwho-2026669

ABSTRACT

Summary: COVID-19 has been associated with factors such as inflammation, obesity, low vitamin D levels, and hyperandrogenism. These factors are also directly related to Polycystic ovary syndrome (PCOS). We hypothesize that concurrent COVID-19 and high dose vitamin D supplement will decrease the inflammation, and can increase the chances of fertility in these women. [ FROM AUTHOR] Copyright of Anaesthesia, Pain & Intensive Care is the property of Department of Anaesthesia, Pain & Intensive Care and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

16.
Iranian Red Crescent Medical Journal ; 24(6), 2022.
Article in English | CAB Abstracts | ID: covidwho-2026568

ABSTRACT

Background: By the end of May 2021, 170 million cases and 3.54 million death from Covid-19 infection have been reported. The high affinity of virus particles to ACE-2 receptors in different body organs can cause varied clinical manifestations and complications. Ischemic colitis and necrosis are some rare complications of Covid-19 infection with high morbidity and mortality resulting from colonic hypoperfusion. Different underlying mechanisms for ischemic colitis in Covid-19 patients have been described, including hypercoagulable state, inflammatory responses, microthrombosis, and non-occlusive intestinal ischemia due to shock, hypoxemia, and low cardiac output. Case Presentation: here, we presented three patients with ischemic colitis and one rectal necrosis as a rare presentation of gastrointestinal complication of SARS-CoV-2 infection. All of our patients presented with abdominal pain and tenderness and received a standard regimen of antibiotics, anticoagulation, and ventilation support.

17.
Acta Biomedica Scientifica ; 7(2):12-23, 2022.
Article in Russian | Scopus | ID: covidwho-2026437

ABSTRACT

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need ofcreating the optimaltactics ofefficientandsafe anti-inflammatory therapy. Anew methodoftreatment ofCOVID-19withinhalation ofultra-low (non-cytotoxic)doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma. The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage. Materials andmethods. A prospective, open, controlled, blindfor the centralexpert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients ofthe control group were selectedby an independentexpertretrospectively using the computer algorithm for selecting“close” patients based on the “case-control” principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning ofinhalations in the melphalan group andfrom the corresponding day in the control group. Results. Inhalations of melphalan led to a significant improvement in the clinical condition ofpatients according to the WHOscale, decrease in the intensity ofdyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group. Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage. © 2022 by the Author(s).

18.
Fiziologichnyi Zhurnal ; 68(3):24-34, 2022.
Article in Ukrainian | Scopus | ID: covidwho-2025781

ABSTRACT

Coronavirus (SARS-CoV-2) enters the cell by binding to a transmembrane glycoprotein, angiotensin-converting en-zyme-2 (ACE2), which is expressed on the surface of the bronchial and alveolar epithelium. In this regard, the aim of this study was to determine changes in the content and characteristics of tissue localization of ACE2 in the model of acute bronchopulmonary inflammation. The latter was modeled by endotracheal injection of a foreign body (Capron thread) and a solution of lipopolysaccharide (LPS;50 μl at a dose of 12.5 mg/kg) against the background of systemic administration of LPS for two days before surgery (250 mg/ kg). ACE2 localization and quantity were evaluated by im-munohistochemical and western blot assays with the use of a specific monoclonal antibody. The experiment reproduced acute exudative-hemorrhagic bronchopneumonia with the development of diffuse progressive pulmonary fibrosis with lethality in 36% of animals. Acute exudative inflammation was accompanied by complete inhibition of ACE2 expression in bronchial epitheliocytes and its significant decrease in alveolocytes type II. With the development of the proliferative stage of bronchopneumonia, the level of ACE2 was restored, subsequently remaining without significant changes. The obtained experimental data suggest the existence of a relationship between the features of quantitative changes in the ACE2 level in the bronchopulmonary epithelium and the undulating course of the inflammatory process during SARS-CoV-2 infection. © 2022, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine. All rights reserved.

19.
Zoonoses ; 2(19), 2022.
Article in English | CAB Abstracts | ID: covidwho-2025752

ABSTRACT

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

20.
Elife ; 11, 2022.
Article in English | PubMed | ID: covidwho-2025329

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

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