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1.
Int J Mol Sci ; 23(11)2022 May 30.
Article in English | MEDLINE | ID: covidwho-1869639

ABSTRACT

The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus' variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing/genetics , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Ferritins/genetics , Humans , Immunity , Mutation , SARS-CoV-2 , Vaccines, Combined
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314187

ABSTRACT

Background: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020. Methods: We collected 52,684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns. Results: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020. Conclusions: The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314174

ABSTRACT

Many people are being hospitalized and are dying from COVID-19 as the right treatment has not yet been identified. We investigate the factors related to the severity and mortality of COVID-19 using big data-machine learning techniques. This retrospective study included 8070 SARS-CoV-2 confirmed patients of the 129,120 SARS-CoV-2 RNA tested patients in South Korea between January and July 2020, and whose data were available from the National Health Insurance Service. Primary endpoint was comorbidity, severity and mortality rate in COVID-19. Machine learning algorithms were performed to evaluate the effects of comorbidities on severity and mortality rate of COVID-19. The most common comorbidities of COVID-19 were pulmonary inflammation followed by anosmia. The model that best predicted severity was a neural network (AUC: 85.06%). The most important variable for predicting severity in the neural network model was a history of influenza (relative importance: 0.129). The model that best predicted mortality was the logistic regression elastic net (EN) model (AUC: 93.86%). The most important variables for mortality in the EN model were age (coefficient: 2.136) and anosmia (coefficient: –1.438). Through the state-of-the-art machine learning algorithm and 8070 patients of COVID-19 patients in South Korea, influenza was found to be a major adverse factor in addition to old age and male sex. In addition, anosmia was found to be a major factor associated with lower severity and mortality rates. The patient’s history of influenza and anosmia will be an important indicator for predicting the severity and mortality of COVID-19 patients.

4.
Int J Mol Sci ; 22(16)2021 Aug 10.
Article in English | MEDLINE | ID: covidwho-1662670

ABSTRACT

Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome-lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome-lysosome fusion.


Subject(s)
Cathepsin L/physiology , Hypoxia-Inducible Factor 1, alpha Subunit/physiology , Melanosomes/metabolism , Animals , Cathepsin L/genetics , Cell Hypoxia/genetics , Cells, Cultured , Gene Expression Regulation , Melanocytes/metabolism , Mice , NIH 3T3 Cells
5.
Int J Mol Sci ; 22(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572495

ABSTRACT

The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has upended healthcare systems and economies around the world. Rapid understanding of the structural biology and pathogenesis of SARS-CoV-2 has allowed the development of emergency use or FDA-approved vaccines and various candidate vaccines. Among the recently developed SARS-CoV-2 candidate vaccines, natural protein-based nanoparticles well suited for multivalent antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses are currently being investigated. This mini-review presents recent innovations in protein-based nanoparticle vaccines against SARS-CoV-2. The design and strategy of displaying antigenic domains, including spike protein, receptor-binding domain (RBD), and other domains on the surface of various protein-based nanoparticles and the performance of the developed nanoparticle-based vaccines are highlighted. In the final part of this review, we summarize and discuss recent advances in clinical trials and provide an outlook on protein-based nanoparticle vaccines.


Subject(s)
COVID-19 Vaccines/immunology , Nanoparticles/chemistry , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigen Presentation/immunology , COVID-19/immunology , COVID-19 Vaccines/pharmacology , Humans , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vaccines/immunology
8.
Influenza Other Respir Viruses ; 15(6): 721-731, 2021 11.
Article in English | MEDLINE | ID: covidwho-1360496

ABSTRACT

BACKGROUND: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020. METHODS: We collected 52 684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns. RESULTS: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020. CONCLUSIONS: The COVID-19 pandemic impacted the respiratory virus detection rate. The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.


Subject(s)
COVID-19 , Influenza, Human , Respiratory Tract Infections , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Pandemics , Republic of Korea/epidemiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Rhinovirus/genetics , SARS-CoV-2
9.
Osong Public Health Res Perspect ; 11(3): 112-117, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-844605

ABSTRACT

OBJECTIVES: Coronavirus Disease-19 (COVID-19) is a respiratory infection characterized by the main symptoms of pneumonia and fever. It is caused by the novel coronavirus severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), which is known to spread via respiratory droplets. We aimed to determine the rate and likelihood of SARS-CoV-2 transmission from COVID-19 patients through non-respiratory routes. METHODS: Serum, urine, and stool samples were collected from 74 hospitalized patients diagnosed with COVID-19 based on the detection of SARS-CoV-2 in respiratory samples. The SARS-CoV-2 RNA genome was extracted from each specimen and real-time reverse transcription polymerase chain reaction performed. CaCo-2 cells were inoculated with the specimens containing the SARS-COV-2 genome, and subcultured for virus isolation. After culturing, viral replication in the cell supernatant was assessed. RESULTS: Of the samples collected from 74 COVID-19 patients, SARS-CoV-2 was detected in 15 serum, urine, or stool samples. The virus detection rate in the serum, urine, and stool samples were 2.8% (9/323), 0.8% (2/247), and 10.1% (13/129), and the mean viral load was 1,210 ± 1,861, 79 ± 30, and 3,176 ± 7,208 copy/µL, respectively. However, the SARS-CoV-2 was not isolated by the culture method from the samples that tested positive for the SARS-CoV-2 gene. CONCLUSION: While the virus remained detectable in the respiratory samples of COVID-19 patients for several days after hospitalization, its detection in the serum, urine, and stool samples was intermittent. Since the virus could not be isolated from the SARS-COV-2-positive samples, the risk of viral transmission via stool and urine is expected to be low.

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