Effect of the interval between birth and second dose of hepatitis B vaccine on perinatal transmission of hepatitis B virus.

Preventing perinatal transmission is important for hepatitis B (HepB) elimination. We conducted a retrospective cohort study to assess the interval between HepB birth-dose (HepB-BD) to second-dose (HepB-SD) vaccination on perinatal transmission. Among 39,313 infants born to HepB s-antigen (HBsAg)-positive mothers from a Korean national database 38,411 (97.7%) had completed timely immunophylaxis with HepB-BD 41,572 (99.8%) with hepatitis B immune globulin, and 1027 (2.6%) were HBsAg-positive at ≥ 9 months. Maternal factors (i.e. HepB e-antigen status, age, or nationality) were associated with an increased risk of infection whereas short gestational length decreased it. The HepB-BD - HepB-SD interval (<8 vs. ≥8 weeks) did not alter the risk.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Comparison of Waning Neutralizing Antibody Responses Against the Omicron Variant 6 Months After Natural Severe Acute Respiratory Syndrome Coronavirus 2 Infection (With or Without Subsequent Coronavirus Disease 2019 [COVID-19] Vaccination) Versus 2-Dose COVID-19 Vaccination.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, subsequent ChAdOx1 nCoV-19 vaccination induced similar neutralizing antibody levels against the original strain but significantly higher levels against the Omicron variant compared to those who were not vaccinated. Prior SARS-CoV-2 infection exhibited higher neutralization antibody titers than vaccination alone for both original strains and the Omicron variant.

Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.

BACKGROUND: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. METHOD: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. RESULTS: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. CONCLUSIONS: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.

Inclusion of hepatitis C virus testing in National Health Screening to accelerate HCV elimination in South Korea.

In 2015, the World Health Organization (WHO) has set the goal of eliminating hepatitis C by reducing incidence of chronic viral hepatitis and related mortality by 2030 with the interim target of achieving 30% prevalence reduction by 2020. While The global prevalence of hepatitis C is known to be around 1.6%, the prevalence of hepatitis C in South Korea is 0.5-0.6% based on hepatitis C virus (HCV) antibody-positive rate. Although HCV antibody test has been included in the Annual National Health and Nutrition Survey in South Korea since 2012, a national initiative to eliminate hepatitis C was initiated by small clinic-related hepatitis C outbreaks in 2015-2016. These outbreaks caused by inappropriate use of syringes in 2015-2016 prompted the revision of hepatitis C reporting and control strategies in Korea following long-term discussion on including the HCV antibody test in the National Health Screening at a certain age. Since June 3, 2017, all hepatitis C cases should be reported to the Korea Disease Control Agency (KDCA). A pilot study for early detection of hepatitis C was conducted for the 56 years old population from September 1 to October 31 in 2020 by temporarily including HCV Ab in the National Health Screening followed by HCV RNA testing for HCV antibody positive cases. The final decision to include HCV antibody test in National Health Screening will be made based on results of the pilot study in 2020. To eliminate hepatitis B & C by 2030 in South Korea, the KDCA established a comprehensive viral hepatitis control and management system in 2020 with the interim goal of achieving an antibody positive rate of 0.3% and treatment rate of 90% by 2025.

Report of the Korean Society of Infectious Diseases Roundtable Discussion on Responses to the Measles Outbreaks in Korea in 2019.

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than non-response considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions. Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

Comparison of Antibody and T Cell Responses Induced by Single Doses of ChAdOx1 nCoV-19 and BNT162b2 Vaccines.

There are limited data directly comparing humoral and T cell responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines. We compared Ab and T cell responses after first doses of ChAdOx1 nCoV-19 vs. BNT162b2 vaccines. We enrolled healthcare workers who received ChAdOx1 nCoV-19 or BNT162b2 vaccine in Seoul, Korea. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein-specific IgG Abs (S1-IgG), neutralizing Abs (NT Abs), and SARS-CoV-2-specific T cell response were evaluated before vaccination and at 1-wk intervals for 3 wks after vaccination. A total of 76 persons, comprising 40 injected with the ChAdOx1 vaccine and 36 injected with the BNT162b2 vaccine, participated in this study. At 3 wks after vaccination, the mean levels (±SD) of S1-IgG and NT Abs in the BNT162b2 participants were significantly higher than in the ChAdOx1 participants (S1-IgG, 14.03±7.20 vs. 6.28±8.87, p<0.0001; NT Ab, 183.1±155.6 vs. 116.6±116.2, p=0.035), respectively. However, the mean values of the T cell responses in the 2 groups were comparable after 2 wks. The humoral immune response after the 1st dose of BNT162b2 developed faster and was stronger than after the 1st dose of ChAdOx1. However, the T cell responses to BNT162b2 and ChAdOx1 were similar.

TMPRSS2 and RNA-Dependent RNA Polymerase Are Effective Targets of Therapeutic Intervention for Treatment of COVID-19 Caused by SARS-CoV-2 Variants (B.1.1.7 and B.1.351).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of the coronavirus disease 2019 (COVID-19) pandemic, and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development, and this effort was partially successful. Since the beginning of the COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world, and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. Viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development; therefore, the inhibitory effects of transmembrane serine protease 2 (TMPRSS2) and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the United Kingdom and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern. IMPORTANCE The COVID-19 pandemic is causing unprecedented global problems in both public health and human society. While some vaccines and monoclonal antibodies were successfully developed very quickly and are currently being used, numerous variants of the causative SARS-CoV-2 are emerging and threatening the efficacy of vaccines and monoclonal antibodies. In order to respond to this challenge, we assessed antiviral efficacy of small-molecule inhibitors that are being developed for treatment of COVID-19 and found that they are still very effective against the SARS-CoV-2 variants. Since most small-molecule inhibitors target viral or host factors other than the mutated sequence of the viral spike protein, they are expected to be potent control measures against the COVID-19 pandemic.

Correlation between Reactogenicity and Immunogenicity after the ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccination.

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea.

We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset.

A new Korean Research Investment for Global Health Technology (RIGHT) Fund to advance innovative neglected-disease technologies.

In 2018, the government of the Republic of Korea (ROK), South Korean life science companies, and a group of international funders led by the Bill & Melinda Gates Foundation launched a new and innovative funding agency to support neglected-disease research and development (R&D). The new venture is known as the Research Investment for Global Health Technology (RIGHT) Fund.

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study.

INTRODUCTION: Hepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol. METHODS: A retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013. RESULTS: During the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period. CONCLUSIONS: A substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.

WHO International Health Regulations Emergency Committee for the COVID-19 outbreak.

To discuss whether the coronavirus disease 2019 (COVID-19) outbreak constitutes a Public Health Emergency of International Concern (PHEIC), World Health Organization (WHO) organized the 15-member International Health Regulations Emergency Committee (EC). On January 22-23 and January 30, 2020, EC convened and discussed whether the situation in China and other countries would constitute PHEIC and issued recommendations for WHO, China and the international community. Based on the recommendations of EC, WHO declared the COVID-19 outbreak a PHEIC. One of the purposes of the declaration of PHEIC was to alarm countries with weak public health infrastructures to prepare promptly for emerging infectious diseases (EID) and provide WHO with a framework for proactively supporting those countries. On February 3, 2020, WHO proposed the 2019 COVID-19 Strategic Preparedness and Response Plan, which includes accelerating research and development (R&D) processes as one of three major strategies. On February 11-12, 2020, WHO held the Global Research and Innovation Forum: Towards a Research Roadmap for COVID-19. The fact that a COVID-19 R&D forum was the first meeting convened after the PHEIC declaration testifies to the importance of R&D in response to EID. Korea has demonstrated a remarkable capacity in its laboratory response by conducting high-throughput COVID-19 testing and utilizing innovative drive-through samplings. These measures for early detection and screening of cases should be followed by full efforts to produce research-based evidence by thoroughly analyzing epidemiological, clinical and immunological data, which will facilitate the development of vaccines and therapeutics for COVID-19. It is expected that Korea plays a global partner for COVID-19 research by actively participating in immediate and mid/long-term priorities jointly led by WHO and global partners.

Japanese encephalitis in the Western Pacific Region: Implication from the Republic of Korea.

Japanese encephalitis (JE) is endemic in the Western Pacific Region. We aim to describe the regional status of control of JE, based on the World Health Organization (WHO) surveillance data, and to share the experience from the Republic of Korea. Substantial progress has been made in the region to date; however, epidemiologic changes have not been delineated. The vaccination coverage should be addressed to close the immunity gap. The lessons learned from Korea may aid in establishing a high-quality surveillance system with a sustainable JE vaccination program in order to prepare for new challenges that this region will face.