• Journal of Preventive Medicine and Public Health
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• v.56 no.6
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• pp.542-551
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• 2023

Objectives: Prospective studies on vaccination status and mortality related to coronavirus disease 2019 (COVID-19) in low-resource settings are still limited. We assessed the association between vaccination status (full, partial, or none) and in-hospital mortality among COVID-19 patients at most hospitals in Jakarta, Indonesia during the Delta predomination wave. Methods: We conducted a retrospective cohort study among hospitalized COVID-19 patients who met the study criteria (>18 years old and admitted for inpatient treatment because of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection). We linked individual-level data in the hospital admission database with vaccination records. Several socio-demographic and clinical characteristics were also analyzed. A Cox proportional hazards regression model was used to explore the association between vaccination status and in-hospital mortality in this patient group. Results: In total, 40 827 patients were included in this study. Of these, 70% were unvaccinated (n=28 543) and 19.3% (n=7882) died during hospitalization. The mean age of the patients was 49 years (range, 35-59), 53.2% were female, 22.0% had hypertension, and 14.2% were treated in the intensive care unit, and the median hospital length of stay across the group was 9 days. Our study showed that the risk of in-hospital mortality among fully and partially vaccinated patients was lower than among unvaccinated adults (adjusted hazard ratio [aHR], 0.43; 95% confidence interval [CI], 0.40 to 0.47 and aHR, 0.70; 95% CI, 0.64 to 0.77, respectively). Conclusions: Vaccinated patients had fewer severe outcomes among hospitalized adults during the Delta wave in Jakarta. These features should be carefully considered by healthcare professionals in treating adults within this patient group.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.265-290
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• 2023

Rare but serious thrombotic incidents in relation to thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), have been observed since the vaccine rollout, particularly among replication-defective adenoviral vector-based severe acute respiratory syndrome coronavirus 2 vaccine recipients. Herein, we comprehensively reviewed and summarized reported studies of VITT following the coronavirus disease 2019 (COVID-19) vaccination to determine its prevalence, clinical characteristics, as well as its management. A literature search up to October 1, 2021 using PubMed and SCOPUS identified a combined total of 720 articles. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline, after screening the titles and abstracts based on the eligibility criteria, the remaining 47 full-text articles were assessed for eligibility and 29 studies were included. Findings revealed that VITT cases are strongly related to viral vector-based vaccines, which are the AstraZeneca COVID-19 vaccine (95%) and the Janssen COVID-19 vaccine (4%), with much rarer reports involving messenger RNA-based vaccines such as the Moderna COVID-19 vaccine (0.2%) and the Pfizer COVID-19 vaccine (0.2%). The most severe manifestation of VITT is cerebral venous sinus thrombosis with 317 cases (70.4%) and the earliest primary symptom in the majority of cases is headache. Intravenous immunoglobulin and non-heparin anticoagulant are the main therapeutic options for managing immune responses and thrombosis, respectively. As there is emerging knowledge on and refinement of the published guidelines regarding VITT, this review may assist the medical communities in early VITT recognition, understanding the clinical presentations, diagnostic criteria as well as its management, offering a window of opportunity to VITT patients. Further larger sample size trials could further elucidate the link and safety profile.

• Korean Circulation Journal
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• v.54 no.6
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• pp.295-310
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• 2024

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has led to a global health crisis with substantial mortality and morbidity. To combat the COVID-19 pandemic, various vaccines have been developed, but unexpected serious adverse events including vaccine-induced thrombotic thrombocytopenia, carditis, and thromboembolic events have been reported and became a huddle for COVID-19 vaccination. Vaccine-related myocarditis (VRM) is a rare but significant adverse event associated primarily with mRNA vaccines. This review explores the incidence, risk factors, clinical presentation, pathogenesis, management strategies, and outcomes associated with VRM. The incidence of VRM is notably higher in male adolescents and young adults, especially after the second dose of mRNA vaccines. The pathogenesis appears to involve an immune-mediated process, but the precise mechanism remains mostly unknown so far. Most studies have suggested that VRM is mild and self-limiting, and responds well to conventional treatment. However, a recent nationwide study in Korea warns that severe cases, including fulminant myocarditis or death, are not uncommon in patients with COVID-19 VRM. The long-term cardiovascular consequences of VRM have not been well understood and warrant further investigation. This review also briefly addresses the critical balance between the substantial benefits of COVID-19 vaccination and the rare risks of VRM in the coming endemic era. It emphasizes the need for continued surveillance, research to understand the underlying mechanisms, and strategies to mitigate risk. Filling these knowledge gaps would be vital to refining vaccination recommendations and improving patient care in the evolving COVID-19 pandemic landscape.

• BMB Reports
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• v.40 no.5
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• pp.649-655
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• 2007

The nsp14 protein is an exoribonuclease that is encoded by severe acute respiratory syndrome coronavirus (SARS-CoV). We have cloned and expressed the nsp14 protein in Escherichia coli, and characterized the nature and the role(s) of the metal ions in the reaction chemistry. The purified recombinant nsp14 protein digested a 5'-labeled RNA molecule, but failed to digest the RNA substrate that is modified with fluorescein group at the 3'-hydroxyl group, suggesting a 3'-to-5' exoribonuclease activity. The exoribonuclease activity requires $Mg^{2+}$ as a cofactor. Isothermal titration calorimetry (ITC) analysis indicated a two-metal binding mode for divalent cations by nsp14. Endogenous tryptophan fluorescence and circular dichroism (CD) spectra measurements showed that there was a structural change of nsp14 when binding with metal ions. We propose that the conformational change induced by metal ions may be a prerequisite for catalytic activity by correctly positioning the side chains of the residues located in the active site of the enzyme.

• Safety and Health at Work
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• v.11 no.3
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• pp.262-265
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• 2020

Coronavirus disease 2019 (Covid-19) poses an important occupational health risk to health workers (HWs) that has attracted global scrutiny. To date, several thousand HWs globally have been reported as infected with the severe acute respiratory syndrome coronavirus 2 virus that causes the disease. It is therefore a public health priority for policymakers to understand risk factors for this vulnerable group to avert occupational transmission. A rapid review was carried out on 20 April 2020 on Covid-19 risk factors among HWs in PubMed, Google Scholar, and EBSCOHost Web (Academic Search Complete, CINAHL Complete, MEDLINE with Full Text, CINAHL with Full Text, APA PsycInfo, Health Source-Consumer Edition, Health Source: Nursing/Academic Edition) and WHO Global Database. We also searched for preprints on the medRxiv database. We searched for reports, reviews, and primary observational studies (case control, case cross-over, cross-sectional, and cohort). The review included studies conducted among HWs with Covid-19 that reported risk factors irrespective of their sample size. Eleven studies met the inclusion criteria. Lack of personal protective equipment, exposure to infected patients, work overload, poor infection control, and preexisting medical conditions were identified as risk factors for Covid-19 among HWs. In the context of Covid-19, HWs face an unprecedented occupational risk of morbidity and mortality. There is need for rapid development of sustainable measures that protect HWs from the pandemic.

• BMB Reports
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• v.38 no.4
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• pp.381-385
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• 2005

Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a novel coronavirus (CoV) that was identified and molecularly characterized in 2003. Previous studies on various coronaviruses indicate that protein-protein interactions amongst various coronavirus proteins are critical for viral assembly and morphogenesis. It is necessary to elucidate the molecular mechanism of SARS-CoV replication and rationalize the anti-SARS therapeutic intervention. In this study, we employed an in vitro GST pull-down assay to investigate the interaction between the membrane (M) and the nucleocapsid (N) proteins. Our results show that the interaction between the M and N proteins does take place in vitro. Moreover, we provide an evidence that 12 amino acids domain (194-205) in the M protein is responsible for binding to N protein. Our work will help shed light on the molecular mechanism of the virus assembly and provide valuable information pertaining to rationalization of future anti-viral strategies.

• Molecules and Cells
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• v.44 no.9
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• pp.680-687
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• 2021

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing.

• Genomics & Informatics
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• v.18 no.4
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• pp.43.1-43.13
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• 2020

The coronavirus disease 2019 is a contagious disease and had caused havoc throughout the world by creating widespread mortality and morbidity. The unavailability of vaccines and proper antiviral drugs encourages the researchers to identify potential antiviral drugs to be used against the virus. The presence of RNA binding domain in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be a potential drug target, which serves multiple critical functions during the viral life cycle, especially the viral replication. Since vaccine development might take some time, the identification of a drug compound targeting viral replication might offer a solution for treatment. The study analyzed the phylogenetic relationship of N protein sequence divergence with other 49 coronavirus species and also identified the conserved regions according to protein families through conserved domain search. Good structural binding affinities of a few natural and/or synthetic phytocompounds or drugs against N protein were determined using the molecular docking approaches. The analyzed compounds presented the higher numbers of hydrogen bonds of selected chemicals supporting the drug-ability of these compounds. Among them, the established antiviral drug glycyrrhizic acid and the phytochemical theaflavin can be considered as possible drug compounds against target N protein of SARS-CoV-2 as they showed lower binding affinities. The findings of this study might lead to the development of a drug for the SARS-CoV-2 mediated disease and offer solution to treatment of SARS-CoV-2 infection.

• Genomics & Informatics
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• v.18 no.4
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• pp.44.1-44.7
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• 2020

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from Global Initiative on Sharing Avian Influenza Data (GISAID) database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14408C>T and 23403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p < 0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group (p < 0.001). The 3037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group compared with mildly affected group, but the difference was not statistically significant (p = 0.06). We concluded that spike protein D614G and RdRp P323L mutations in SARS-CoV-2 are associated with severity of COVID-19. Further studies will be required to explore whether these mutations have any impact on the severity of disease.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.1
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• pp.65-74
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• 2021

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has influenced the lives of people worldwide. Little is known about the effects of the COVID-19 pandemic on the behavior and fears of pediatric patients with inflammatory bowel disease (IBD) and their families. We conducted a survey to determine the COVID-19 exposure, related perceptions, and information sources; medication compliance; and patients' and parents' behaviors, fears, and physician contact. Methods: An anonymous cross-sectional survey of pediatric patients with IBD and their parents at one pediatric gastroenterology unit of a university medical center was performed. Results: A total of 46 pediatric patients with IBD and 44 parents completed the survey. Parents of pediatric patients with IBD had high fear of their children becoming infected with severe acute respiratory syndrome coronavirus 2. They perceived schools as the most hazardous environment, whereas the children did not. Half the pediatric patients with IBD feared infection. Patients and parents felt sufficiently informed about COVID-19. The primary source of guidance for pediatric patients was their parents (43%), followed by television and social media, whereas the parents mainly consulted internet news websites (52.2%), television, and public health institutes. Pediatric patients with IBD adhered to their prescribed medication. They also showed cautious behavior by enhancing hand hygiene (84%) and leaving the house less frequently than before. However, in-person medical visits remained favored over video consultations. Conclusion: Although parents expressed overprotective concerns, both parents and pediatric patients with IBD are coping well with the COVID-19 pandemic. IBD-relevant information should be actively conveyed.