• The Korean journal of internal medicine
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• v.39 no.1
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• pp.160-171
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• 2024

Background/Aims: The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. Results: A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I² = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. Conclusions: In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilator support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.77-83
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• 2022

A small proportion of children with coronavirus disease 2019 (COVID-19) develop severe pneumonia. We reported the severe COVID-19 pneumonia in children aged <18 years with COVID-19 treated with remdesivir and dexamethasone from August 2021 to November 2021 by a retrospective review of their medical records. Eight children were included (5 males and 3 females). Their median age was 16 years (range: 9 to 17 years) and their median body mass index was 30.5 kg/m² (range: 22.8-38.5 kg/m²). All patients had fever and dyspnea with hypoxia. Chest radiographic findings were variable and included diffuse or multifocal consolidation, nodules, and ground-glass opacities in the lungs. After receiving intravenous remdesivir and dexamethasone, 7 of the 8 children experienced an improvement in their symptoms within 2 days. In our case series, obesity was present in 6 out of 8 children with severe COVID-19 pneumonia.

• Journal of Plant Biotechnology
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• v.48 no.4
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• pp.289-303
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• 2021

Covid-19 is an ongoing pandemic as we speak in 2022. This infectious disease is caused by the SARS-CoV-2 virus, which infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. Thus, strategies that inhibit the binding of SARS-CoV-2 to the ACE2 receptor can stop this contagion. Hanjeli (Coix lacryma-jobi) essential oil contains many bioactive compounds, including dodecanoic acid; tetradecanoic acid; 7-Amino-8-imino-2-(2-imino-2H-chromen-3-yl); and 1,5,7,10-tetraaza-phen-9-one. These compounds suppress viral replication and may prevent Covid-19. Accordingly, this study assessed whether, these four limonoid compounds can block the ACE2 receptor. To this end, their physicochemical properties were predicted using Lipinski's "rule of five" on the SwissADME website, and their toxicity was assessed using the online tools ProTox and pkCSM. Additionally, their interactions with the ACE2 receptor were predicted via molecular docking using Autodock Vina. All the four compounds satisfied the "rule of five" and tetradecanoic acid was predicted to have a higher affinity than the comparison compound remdesivir and the original ligand of ACE2. Molecular docking results suggested that the compounds from hanjeli essential oil interact with the active site of the ACE2 receptor similarly as the original ligand and remdesivir. In conclusion, hanjeli essential oil contains compounds predicted hinder the interaction of SARS-CoV-2 with the ACE2 receptor. Accordingly, our data may facilitate the development of a phytomedical strategy against SARS-CoV-2 infection.

• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.

• Journal of Pharmacopuncture
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• v.23 no.2
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• pp.62-70
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• 2020

Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Currently, the management of patients with COVID-19 depends mainly on repurposed drugs which include chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, remdesivir, favipiravir, umifenovir, interferon-α, interferon-β and others. In this review, the potential of Nigella sativa (black cumin seeds) to treat the patients with COVID-19 analyzed, as it has shown to possess antiviral, antioxidant, anti-inflammatory, anticoagulant, immunomodulatory, bronchodilatory, antihistaminic, antitussive, antipyretic and analgesic activities. Medline/PubMed Central/PubMed, Google Scholar, Science Direct, Directory of open access journals (DOAJ) and reference lists were searched to identify articles associated with antiviral and other properties of N.sativa related to the signs and symptoms of COVID-19. Various randomized controlled trials, pilot studies, case reports and in vitro and in vivo studies confirmed that N.sativa has antiviral, antioxidant, anti-inflammatory, immunomodulatory, bronchodilatory, antihistaminic, antitussive activities related to causative oraganism and signs and symptoms of COVID-19. N. sativa could be used as an adjuvant therapy along with repurposed conventional drugs to manage the patients with COVID-19.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.50-55
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• 2021

Low-dose radiotherapy has been known to have anti-inflammatory activity and been used for treatment of pneumonia together with anti-serum and sulfanilamide. However, it rapidly discontinued after the development of various antibiotics showing outstanding effect. Recently, it was re-considered to treat COVID-19 which has very limited treatment such as remdesivir and dexamethasone. So, several studies of COVID-19 therapy using low-dose radiation were reported very recently. They showed that low-dose radiation of 0.5~1.5 Gy were useful for decreasing the oxygen consumption and hospitalization period of COVID-19 patients without adverse reaction. Radiopharmaceuticals such as [⁹⁹mTc]Tc-macroaggregated albumin (MAA) also might be used for low-dose radiotherapy. Administration of vitamin D having anti-inflammatory effect would also be helpful for therapy with synergistic effect.

• 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.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.252-266
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• 2020

The coronavirus disease 2019 (COVID-19) is a highly contagious pneumonia that has spread throughout the world. It is caused by a novel, single stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Genetic analysis revealed that, phylogenetically, the SARS-CoV-2 is related to severe acute respiratory syndrome-like viruses seen in bats. Because of this, bats are considered as a possible primary reservoir. The World Health Organization has declared the COVID-19 outbreak as a pandemic. As of May 27, 2020, more than 5,406,282 confirmed cases, and 343,562 confirmed deaths have been reported worldwide. Currently, there are no approved vaccines or antiviral drugs available against COVID-19. Newly developed vaccines are in the first stage of clinical trials, and it may take a few months to a few years for their commercialization. At present, remdesivir and chloroquine are the promising drugs for treating COVID-19 patients. In this review, we summarize the diversity, genetic variations, primary reservoirs, epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment strategies, and future prospects with respect to controlling the spread of COVID-19.

• Pediatric Infection and Vaccine
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• v.29 no.3
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• pp.155-160
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• 2022

Children and adolescents with coronavirus disease 2019 (COVID-19) generally have mild symptoms. Severe infection due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) involving multiorgan dysfunction is rare in this population. Herein, we present an unusual case of severe SARS-CoV-2 infection with multiorgan involvement followed by multisystem inflammatory syndrome in children (MIS-C) in a vaccinated 16-year-old boy. The patient was unconscious on initial presentation, and had severe paralytic ileus. On laboratory examination, there was severe metabolic acidosis, lymphocytopenia, thrombocytopenia, elevated inflammatory markers, elevated liver enzymes, and evidence of acute kidney injury with proteinuria and hematuria. His symptoms improved with the administration of remdesivir and dexamethasone. The patient briefly experienced MIS-C 2 weeks after the diagnosis of COVID-19, but the patient was discharged without any complications.

• Pediatric Infection and Vaccine
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• v.29 no.3
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• pp.147-154
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• 2022

The clinical severity of coronavirus disease 2019 (COVID-19) in children is usually mild. Most of the affected patients completely recovered from COVID-19 before being released from approximately 7-day quarantine. However, children with comorbidities are at risk of more severe disease and adverse outcomes. We report three cases of COVID-19-affected adolescents with underlying chronic respiratory difficulty due to neurologic diseases who showed sudden clinical aggravations at the time of discharge, even after full clinical improvement. Patient 1 is a 17-year-old boy with Ullrich congenital muscular dystrophy who had cardiopulmonary arrest 9 days after the initial COVID-19 symptoms. Patient 2 is a 17-year-old girl with intracerebral hemorrhage with infarction in bed-ridden status who had cardiopulmonary arrest 11 days after the initial symptoms. Patient 3 is a 12-year-old boy with intraventricular hemorrhage with hydrocephalus in bed-ridden status who showed multiorgan failure 10 days after the initial symptoms. Remdesivir, dexamethasone, and empirical antibiotics were administered with mechanical ventilation and intensive unit care. Among the three patients, two (patients 1 and 3) were alive, and one (patient 2) expired. Clinicians caring for adolescents with chronic neurologic and/or pulmonary disease should keep in mind that these patients could have sudden deterioration after recovery from the acute phase of COVID-19 around or after the time of discharge.