Osong Public Health and Research Perspectives

Original Articles

Effect of Paxlovid in COVID-19 treatment during the periods of SARS-CoV-2 Omicron BA.5 and BN.1 subvariant dominance in the Republic of Korea: a retrospective cohort study: Dong-Hwi Kim, Min-Gyu Yoo, Na-Young Kim, So Young Choi, Minjeong Jang, Misuk An, Se-Jin Jeong, Jungyeon Kim; Received August 16, 2023 Accepted January 18, 2024 Published online March 28, 2024; DOI: https://doi.org/10.24171/j.phrp.2023.0230 [Epub ahead of print]

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Abstract PDF: Objectives
This study was conducted to assess the efficacy of nirmatrelvir/ritonavir treatment in patients with coronavirus disease 2019 (COVID-19), particularly those aged 60 years and older. Using real-world data, the period during which the BN.1 Omicron variant was dominant was compared to the period dominated by the BA.5 variant.
Methods
In this retrospective cohort study, data were collected regarding 2,665,281 patients infected with severe acute respiratory syndrome coronavirus 2 between July 24, 2022, and March 31, 2023. Propensity score matching was utilized to match patients who received nirmatrelvir/ritonavir in a 1:4 ratio between BN.1 and BA.5 variant groups. Multivariable logistic regression analysis was employed to assess the effects of nirmatrelvir/ritonavir within these groups.
Results
Compared to the prior period, the efficacy of nirmatrelvir/ritonavir did not significantly differ during the interval of Omicron BN.1 variant dominance in the Republic of Korea. Among patients treated with nirmatrelvir/ritonavir, a significantly lower risk of mortality was observed in the BN.1 group (odds ratio [OR], 0.698; 95% confidence interval [CI], 0.557–0.875) compared to the BA.5 group. However, this treatment did not significantly reduce the risk of severe or critical illness, including death, for those in the BN.1 group (OR, 0.856; 95% CI, 0.728–1.007).
Conclusion
Nirmatrelvir/ritonavir has maintained its effectiveness against COVID-19, even with the emergence of the BN.1 Omicron subvariant. Consequently, we strongly recommend the administration of nirmatrelvir/ritonavir to patients exhibiting COVID-19-related symptoms, irrespective of the dominant Omicron variant or their vaccination status, to mitigate disease severity and decrease the risk of mortality.

Treatment with Sofosbuvir and Daclatasvir (with or without Ribavirin) Improves Patient Reported Outcomes in Hepatitis C: Lucas Pereira Jorge de Medeiros, Mario Barreto Correa Lima, Marcia Maria Amêndola Pires, Alessandra Mendonça Almeida Maciel, Renata Barboza Vianna Medeiros, Mariana Dermínio Donadel, Isabela Martins Becattini Pereira, Fábio Marchon Leão, Luiz Eduardo Amorim Correa Lima Pires, Helio Rzetelna, Carlos Eduardo Brandão-Mello; Osong Public Health Res Perspect. 2018;9(2):50-58. Published online April 30, 2018; DOI: https://doi.org/10.24171/j.phrp.2018.9.2.03

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Objectives

To evaluate the impact of 3 treatment regimens upon health-related quality of life and work productivity using patient-reported outcomes (PROs) in chronic hepatitis C infected patients: sofosbuvir (SOF) + daclatasvir (DCV); SOF + DCV + ribavirin (RBV); SOF + simeprevir (SMV).

Methods

4 questionnaires were used to evaluate PROs before, during and after treatment: Short Form-36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ) - hepatitis C virus (HCV), Work Productivity and Activity Index, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

Results

Of the global sample of 55 patients included in this study; SOF + DCV (n = 10); SOF + DCV + RBV (n = 29); SOF + SMV (n = 16) all had a statistically significant improvement in SF-36, CLDQ and FACIT-F scores during and post-treatment. No statistically significant differences in the PRO questionnaire values were observed between the distinct treatment regimens. The SOF and SMV patient groups presented higher mean PRO variations during and post-treatment, compared to the other groups: SF-36 functional capacity (16.1); SF-36 mental health (21.4); CLDQ activity (1.8); CLDQ emotional function (1.2); FACIT-F physical well-being (8.0); Total FACIT-F (21.6).

Conclusion

Treatment with SOF + DCV, with or without RBV, results in an improved PRO similar to treatment with SOF + SMV in chronic hepatitis C patients.

Citations

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Brief Reports

In Vitro Antiviral Activity of Sakuranetin against Human Rhinovirus 3: Hwa-Jung Choi; Osong Public Health Res Perspect. 2017;8(6):415-420. Published online December 31, 2017; DOI: https://doi.org/10.24171/j.phrp.2017.8.6.09

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Abstract PDF

Objectives

Rhinoviruses (RVs) cause common cold and are associated with exacerbation of chronic inflammatory respiratory diseases. Until now, no clinically effective antiviral chemotherapeutic agents to treat diseases caused by human rhinoviruses (HRVs) have been reported. We assessed the anti-HRV3 activity of sakuranetin isolated from Sorbus commixta Hedl. in human epithelioid carcinoma cervix (HeLa) cells, to evaluate its anti-rhinoviral potential in the clinical setting.

Methods

Antiviral activity and cytotoxicity as well as the effect of sakuranetin on HRV3-induced cytopathic effects (CPEs) were evaluated using the sulforhodamine B (SRB) method using CPE reduction. The morphology of HRV3-infected cells was studied using a light microscope.

Results

Sakuranetin actively inhibited HRV3 replication and exhibited antiviral activity of more than 67% without cytotoxicity in HeLa cells, at 100 μg/mL. Ribavirin showed anti-HRV3 activity similar to that of sakuranetin. Treatment of HRV-infected HeLa cells with sakuranetin visibly reduced CPEs.

Conclusion

The inhibition of HRV production by sakuranetin is mainly due to its general antioxidant activity through inhibition of viral adsorption. Therefore, the antiviral activity of sakuranetin should be further investigated to elucidate its mode of action and prevent HRV3-mediated diseases in pathological conditions.

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Evaluation of Antiviral Activity of Zanthoxylum Species Against Picornaviruses: Hwa-Jung Choi; Osong Public Health Res Perspect. 2016;7(6):400-403. Published online December 31, 2016; DOI: https://doi.org/10.1016/j.phrp.2016.11.003

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Abstract PDF

Human rhinoviruses and enteroviruses (family Picornaviridae) infect millions of people worldwide each year, but little is known about effective therapeutical treatment for the infection caused by these viruses. We sought to determine whether or not Zanthoxylum (Rutaceae) species can exhibit antiviral activity against picornaviruses. The leaf parts of four Zanthoxylum species were extracted with methanol, and the extracts were investigated for their antiviral activity against picornaviruses using cytopathic effects by cytopathic effect reduction. Leaf extracts of Zanthoxylum piperitum among four Zanthoxylum species were found to possess only broad-spectrum antipicornavirus activity against human rhninovirus 2 with a 50% inhibitory concentration (IC₅₀) value of 59.48 μg/mL, human rhinovirus 3 with an IC₅₀ value of 39.94 μg/mL, coxsackie A16 virus with an IC₅₀ value of 45.80 μg/mL, coxsackie B3 virus with an IC₅₀ value of 68.53 μg/mL, coxsackie B4 virus with an IC₅₀ value of 93.58 μg/mL, and enterovirus 71 virus with an IC₅₀ value of 4.48 μg/mL. However, ribavirin did not possess antiviral activity against human rhinovirus 3 and four enteroviruses. Therefore, leaves of Z. piperitum showed broad-spectrum antipicornavirus activity, and may be useful as a candidate for studying picornavirus agents and development of pharmaceuticals.

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Original Articles

Complete Sequence Analysis and Antiviral Screening of Medicinal Plants for Human Coxsackievirus A16 Isolated in Korea: Jae-Hyoung Song, Kwisung Park, Aeri Shim, Bo-Eun Kwon, Jae-Hee Ahn, Young Jin Choi, Jae Kyung Kim, Sang-Gu Yeo, Kyungah Yoon, Hyun-Jeong Ko; Osong Public Health Res Perspect. 2015;6(1):52-58. Published online February 28, 2015; DOI: https://doi.org/10.1016/j.phrp.2014.12.004

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Abstract PDF

Objectives
Coxsackievirus A group 16 strain (CVA16) is one of the predominant causative agents of hand, foot, and mouth disease (HFMD).
Methods
Using a specimen from a male patient with HFMD, we isolated and performed sequencing of the Korean CVA16 strain and compared it with a G10 reference strain. Also, we were investigated the effects of medicinal plant extract on the cytopathic effects (CPE) by CPE reduction assay against Korean CVA16.
Results
Phylogenetic analysis showed that the Korean CVA16 isolate belonged to cluster B-1 and was closely related to the strain PM-15765-00 isolated in Malaysia in 2000. The Korean CVA16 isolate showed 73.2% nucleotide identity to the G10 prototype strain and 98.7% nucleotide identity to PM-15765-00. Next, we assessed whether the Korean CVA16 isolate could be used for in vitro screening of antiviral agents to treat HFMD infection. Vero cells infected with the Korean CVA16 isolate showed a cytopathic effect 2 days after the infection, and the treatment of cells with Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. davidiana Hemsl extracts exhibited strong antiviral activity against CVA16.
Conclusion
Collectively, our work provides potential candidates for the development of vaccine and novel drugs to treat the CVA16 strain isolated from a Korean patient.

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Assessment of Intensive Vaccination and Antiviral Treatment in 2009 Influenza Pandemic in Korea: Chaeshin Chu, Sunmi Lee; Osong Public Health Res Perspect. 2015;6(1):47-51. Published online February 28, 2015; DOI: https://doi.org/10.1016/j.phrp.2014.11.007

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Abstract PDF

Objectives
We characterized and assessed public health measures, including intensive vaccination and antiviral treatment, implemented during the 2009 influenza pandemic in the Republic of Korea.
Methods
A mathematical model for the 2009 influenza pandemic is formulated. The transmission rate, the vaccination rate, the antiviral treatment rate, and the hospitalized rate are estimated using the least-squares method for the 2009 data of the incidence curves of the infected, vaccinated, treated, and hospitalized.
Results
The cumulative number of infected cases has reduced significantly following the implementation of the intensive vaccination and antiviral treatment. In particular, the intensive vaccination was the most critical factor that prevented severe outbreak.
Conclusion
We have found that the total infected proportion would increase by approximately six times under the half of vaccination rates.

Citations

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Modeling influenza transmission dynamics with media coverage data of the 2009 H1N1 outbreak in Korea
Yunhwan Kim, Ana Vivas Barber, Sunmi Lee, Roberto Barrio
PLOS ONE.2020; 15(6): e0232580. CrossRef
Doing Mathematics with Aftermath of Pandemic Influenza 2009
Hae-Wol Cho, Chaeshin Chu
Osong Public Health and Research Perspectives.2015; 6(1): 1. CrossRef

Assessment of the Intensive Countermeasures in the 2009 Pandemic Influenza in Korea: Jin Hyuk Choi, Yunhwan Kim, Seoyun Choe, Sunmi Lee; Osong Public Health Res Perspect. 2014;5(2):101-107. Published online April 30, 2014; DOI: https://doi.org/10.1016/j.phrp.2014.03.003

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Abstract PDF: Objectives
It is critical to implement effective multiple countermeasures to mitigate or retain the spread of pandemic influenza. We propose a mathematical pandemic influenza model to assess the effectiveness of multiple countermeasures implemented in 2009.
Methods
Age-specific parameters, including the transmission rate, the proportion of asymptomatic individuals, the vaccination rate, the social distancing rate, and the antiviral treatment rate are estimated using the least-square method calibrated to the incidence data.
Results
The multiple interventions (intensive vaccination, social distancing, antivrial treatment) were successfully implemented resulting in the dramatic reduction in the total number of incidence.
Conclusion
The model output is sensitive to age-specific parameters and this leads to the fact that a more elaborate age group model should be developed and extensive further studies must be followed.

Article

The Emergence of Oseltamivir-Resistant Seasonal Influenza A (H1N1) Virus in Korea During the 2008-2009 Season: Woo-Young Choi, Inseok Yang, Sujin Kim, Namjoo Lee, Meehwa Kwon, Joo-Yeon Lee, Chun Kang; Osong Public Health Res Perspect. 2011;2(3):178-185. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.11.042

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Abstract PDF

Objectives
To monitor antiviral drug resistance among seasonal influenza viruses isolated in Korea during the 2008-2009 influenza season, we examined influenza isolates collected through Korea Influenza Surveillance Scheme for antiviral drug susceptibility.
Methods
For genetic analysis of antiviral drug resistance, the matrix (M2) and neuraminidase (NA) genes of each isolate were amplified by reverse transcription-polymerase chain reaction and followed by nucleotide sequencing. For phylogenetic analyses, the sequences of hemagglutinin (HA) and NA genes of each isolate were aligned using multiple alignment program. For phenotypic analysis of antiviral drug resistance, drug susceptibilities against M2 inhibitor (amantadine) and NA inhibitors (oseltavimir and zanamivir) were determined by virus yield reduction assay and fluorometric NA inhibition assay, respectively.
Results
In Korea, the resistant influenza viruses against oseltamivir were first detected in sealsonal influenza A(H1N1) viruses on Week 48 of 2008. Since then, the number of oseltamivir-resistant A(H1N1) viruses was continuously increased and had reached the highest peak on Week 52 of 2008. 533 (99.8%) of 534 A(H1N1) viruses were resistant to oseltamivir and all of them harbored the H275Y mutation in the NA gene during the 2008-2009 season. The oseltamivir resistance identified by sequencing was confirmed by NA inhibition assay. Genetic analysis based on HA gene of the resistant A(H1N1) viruses revealed that the viruses were identified as A/Brisbane/10/2007-like strain which was vaccine strain for the 2008-2009 season.
Conclusions
The oseltamivir-resistant A(H1N1) viruses were first emerged in Europe in November 2007 and then circulated globally. One year later, the oseltamivir-resistant A(H1N1) viruses were first detected in Korea in November 2008 and continued circulating until the Week 7 of 2009 during the 2008-2009 season. Considering the pandemic preparedness, it should be continued to monitor the emergence and the characterization of antiviral drug resistant influenza viruses.

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