• IMMUNE NETWORK
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• v.21 no.5
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• pp.32.1-32.14
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• 2021

Over two hundred twenty-eight million cases of coronavirus disease 2019 (COVID-19) in the world have been reported until the 21^st of September 2021 after the first rise in December 2019. The virus caused the disease called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 4 million deaths blame COVID-19 during the last one year and 8 months in the world. Currently, four SARS-CoV-2 variants of concern are mainly focused by pandemic studies with limited experiments to translate the infectivity and pathogenicity of each variant. The SARS-CoV-2 α, β, γ, and δ variant of concern was originated from United Kingdom, South Africa, Brazil/Japan, and India, respectively. The classification of SARS-CoV-2 variant is based on the mutation in spike (S) gene on the envelop of SARS-CoV-2. This review describes four SARS-CoV-2 α, β, γ, and δ variants of concern including SARS-CoV-2 ε, ζ, η, ι, κ, and B.1.617.3 variants of interest and alert. Recently, SARS-CoV-2 δ variant prevails over different countries that have 3 unique mutation sites: E156del/R158G in the N-terminal domain and T478K in a crucial receptor binding domain. A particular mutation in the functional domain of the S gene is probably associated with the infectivity and pathogenesis of the SARS-CoV-2 variant.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.5.1-5.22
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• 2021

Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.39.1-39.18
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• 2021

The high virulent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in China at the end of 2019 has generated novel coronavirus disease, coronavirus disease 2019 (COVID-19), causing a pandemic worldwide. Every country has made great efforts to struggle against SARS-CoV-2 infection, including massive vaccination, immunological patients' surveillance, and the utilization of convalescence plasma for COVID-19 therapy. These efforts are associated with the attempts to increase the titers of SARS-CoV-2 neutralizing Abs (nAbs) generated either after infection or vaccination that represent the body's immune status. As there is no standard therapy for COVID-19 yet, virus eradication will mainly depend on these nAbs contents in the body. Therefore, serological nAbs neutralization assays become a requirement for researchers and clinicians to measure nAbs titers. Different platforms have been developed to evaluate nAbs titers utilizing various epitopes sources, including neutralization assays based on the live virus, pseudovirus, and neutralization assays utilizing recombinant SARS-CoV-2 S glycoprotein receptor binding site, receptor-binding domain. As a standard neutralization assay, the plaque reduction neutralization test (PRNT) requires isolation and propagation of live pathogenic SARS-CoV-2 virus conducted in a BSL-3 containment. Hence, other surrogate neutralization assays relevant to the PRNT play important alternatives that offer better safety besides facilitating high throughput analyses. This review discusses the current neutralization assay platforms used to evaluate nAbs, their techniques, advantages, and limitations.

• Clinical Nutrition Research
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• v.12 no.4
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• pp.269-282
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• 2023

Vitamin D participates in the biological function of the innate and adaptive immune system and inflammation. We aim to specify the effectiveness of the vitamin D supplementation on the side effects BioNTech, Pfizer vaccination, and immunoglobulin G response against severe acute respiratory syndrome coronavirus 2 in subjects tested positive for coronavirus disease 2019 (COVID-19). In this multi-center randomized clinical trial, 498 people tested positive for COVID-19 were divided into 2 groups, receiving vitamin D capsules or a placebo (1 capsule daily, each containing 600 IU of vitamin D) over 14-16 weeks. Anthropometric indices and biochemical parameters were measured before and after the second dose of vaccination. Fourteen to 16 weeks after supplementation, the intervention group had an immunoglobulin G (IgG) increase of 10.89 ± 1.2 g/L, while the control group had 8.89 ± 1.3 g/L, and the difference was significant between both groups (p = 0.001). After the second dose of vaccination, the supplement group significantly increased their 25-hydroxy vitamin D from initially 28.73 ± 15.6 ng/mL and increased to 46.48 ± 27.2 ng/mL, and the difference between them was significant. Those with a higher body mass index (BMI) had the most of symptoms, and the difference of side effects according to BMI level was significantly different. In 8 weeks after supplementation obese participants had the lowest IgG levels than overweight or normal subjects. The proportion of all types of side effects on the second dose was significantly diminished compared with the first dose in the intervention group. Supplementation of 600 IU of vitamin D3 can reduce post-vaccination side effects and increase IgG levels in participants who received BioNTech, Pfizer vaccine.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.18 no.6
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• pp.1478-1499
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• 2024

Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 become an active epidemic disease due to its spread around the globe. The main causes of the spread are through interaction and transmission of the droplets through coughing and sneezing. The spread can be minimized by isolating the susceptible patients. However, it necessitates remote monitoring to check the breathing issues of the patient remotely to minimize the interactions for spread minimization. Thus, in this article, we offer a wearable-IoTs-centered framework for remote monitoring and recognition of the breathing pattern and abnormal breath detection for timely providing the proper oxygen level required. We propose wearable sensors accelerometer and gyroscope-based breathing time-series data acquisition, temporal features extraction, and machine learning algorithms for pattern detection and abnormality identification. The sensors provide the data through Bluetooth and receive it at the server for further processing and recognition. We collect the six breathing patterns from the twenty subjects and each pattern is recorded for about five minutes. We match prediction accuracies of all machine learning models under study (i.e. Random forest, Gradient boosting tree, Decision tree, and K-nearest neighbor. Our results show that normal breathing and Bradypnea are the most correctly recognized breathing patterns. However, in some cases, algorithm recognizes kussmaul well also. Collectively, the classification outcomes of Random Forest and Gradient Boost Trees are better than the other two algorithms.

• Journal of Microbiology and Biotechnology
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• v.33 no.12
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• pp.1587-1594
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• 2023

Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.151-157
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• 2024

Objective: People vaccinated with the coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) mRNA vaccine have reported experiencing various adverse effects. For instance, reproductive-age women have presented with complaints of abnormal uterine bleeding or menstrual cycle changes. We speculated that differences in basal sex hormone levels before and after vaccination may be present in women who experienced irregular bleeding or menstrual cycle changes; thus, this study aimed to investigate the differences in basal sex hormone levels of women before and after two doses of SARS-CoV-2 mRNA vaccination. Methods: This retrospective study included patients who received SARS-CoV-2 mRNA vaccines between January 2021 and February 2022 at a single center. In an outpatient setting, patients were queried regarding their menstrual cycle, the date of SARS-CoV-2 mRNA vaccination, vaccination type, and vaccination side effects. Differences in basal hormone levels (menstrual cycle days 2-3, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol) before and after vaccination were compared. Results: Among the 326 patients, patients with no laboratory records of the hormones were excluded. The median time interval between SARS-CoV-2 mRNA vaccination and the laboratory test day was 79 days (interquartile range, 44 to 127). A comparative analysis of these hormones before and after vaccination revealed no significant differences. Subgroup analyses based on age and reported adverse events also found no statistically significant differences. Conclusion: This study showed no significant differences in basal hormone levels (FSH, LH, and estradiol) before and after SARS-CoV-2 mRNA vaccination.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.111-120
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• 2016

Asthma is a prevalent and serious health problem in Korea. Recently, the Korean Asthma Guideline has been updated by The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) in an effort to improve the clinical management of asthma. This guideline focuses on adult patients with asthma and aims to deliver up to date scientific evidence and recommendations to general physicians for the management of asthma. For this purpose, this guideline was updated following systematic review and meta-analysis of recent studies and adapting some points of international guidelines (Global Initiative for Asthma [GINA] report 2014, National Asthma Education and Prevention Program [NAEPP] 2007, British Thoracic Society [BTS/SIGN] asthma guideline 2012, and Canadian asthma guideline 2012). Updated issues include recommendations derived using the population, intervention, comparison, and outcomes (PICO) model, which produced 20 clinical questions on the management of asthma. It also covers a new definition of asthma, the importance of confirming various airflow limitations with spirometry, the epidemiology and the diagnostic flow of asthma in Korea, the importance and evidence for inhaled corticosteroids (ICS) and ICS/formoterol as a single maintenance and acute therapy in the stepwise management of asthma, assessment of severity of asthma and management of exacerbation, and an action plan to cope with exacerbation. This guideline includes clinical assessments, and treatment of asthma-chronic obstructive pulmonary disease overlap syndrome, management of asthma in specific conditions including severe asthma, elderly asthma, cough variant asthma, exercise-induced bronchial contraction, etc. The revised Korean Asthma Guideline is expected to be a useful resource in the management of asthma.

• Tuberculosis and Respiratory Diseases
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• v.86 no.2
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• pp.142-149
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• 2023

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global public health threat and different variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. This study aimed to analyse the factors associated with negative conversion of polymerase chain reaction (PCR) and prognosis in critically ill patients according to the SARS-CoV-2 variant. Methods: This study retrospectively analysed 259 critically ill patients with COVID-19 who were admitted to the intensive care unit of a tertiary medical center between January 2020 and May 2022. The Charlson comorbidity index (CCI) was used to evaluate comorbidity, and a negative PCR test result within 2 weeks was used to define negative PCR conversion. The cases were divided into the following three variant groups, according to the documented variant of SARS-CoV-2 at the time of diagnosis: non-Delta (January 20, 2020-July 6, 2021), Delta (July 7, 2021- January 1, 2022), and Omicron (January 30, 2022-April 24, 2022). Results: The mean age of the 259 patients was 67.1 years and 93 (35.9%) patients were female. Fifty (19.3%) patients were smokers, and 50 (19.3%) patients were vaccinated. The CCI (hazard ratio [HR], 1.555; p<0.001), vaccination (HR, 0.492; p=0.033), and Delta variant (HR, 2.469; p=0.002) were significant factors for in-hospital mortality. The Delta variant (odds ratio, 0.288; p=0.003) was associated with fewer negative PCR conversion; however, vaccination (p=0.163) and remdesivir (p=0.124) treatments did not. Conclusion: The Delta variant of SARS-CoV-2 is associated with lower survival and negative PCR conversion. Contrary to expectations, vaccination and remdesivir may not affect negative PCR conversion in critically ill patients with COVID-19.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.18.1-18.15
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• 2022

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.