Long-term humoral and cellular immunity against vaccine strains and Omicron subvariants (BQ.1.1, BN.1, XBB.1, and EG.5) after bivalent COVID-19 vaccination.

Background: The assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy. Methods: This prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination. Results: A total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p<0.001). NAb titers against BQ.1.1, BN.1, and XBB.1 were significantly higher at 9 months post-vaccination than baseline in both groups, whereas NAb against EG.5 was negligible at all time points. The T-cell immune response (median spot forming unit/106 cells) was highly cross-reactive at both baseline (wild-type/BA.5/XBB.1.5, 38.3/52.5/45.0 in SARS-CoV-2-naïve individuals; 51.6/54.9/54.9 in SARS-CoV-2-infected individuals) and 4 weeks post-vaccination, with insignificant boosting post-vaccination. Conclusion: Remarkable cross-reactive neutralization was observed against BQ.1.1, BN.1, and XBB.1 up to 9 months after BA.4/5 bivalent vaccination, but not against EG.5. The T-cell immune response was highly cross-reactive.

Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea.

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported.

Longitudinal immune kinetics of COVID-19 booster versus primary series vaccination: Insight into the annual vaccination strategy.

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9-12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9-12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

Establishment of Safety Monitoring System for Vaccines Not Included in the National Immunization Program in Korea.

BACKGROUND: In Korea, there are no surveillance programs for vaccines that are not included in the national immunization program (NIP), and vaccine safety monitoring in the adult population is inadequate. This study aimed to establish a safety monitoring system for non-NIP vaccines in adults. METHODS: Frequently administered non-NIP vaccines were selected. Individuals were included if they received at least one of the selected vaccines at a participating institution and provided informed consent. Solicited and unsolicited adverse events were monitored using questionnaires sent through text messages on days 1, 3, 7, 28, and 90 post-vaccination. Selected adverse events of special interest (AESIs) were monitored monthly by retrospective review of electronic medical records. Causality was assessed according to the Korea Disease Control and Prevention Agency guidelines. RESULTS: Four vaccines (tetanus-diphtheria-pertussis [Tdap], pneumococcal conjugate 13-valent [PCV13], live zoster vaccine [ZVL], and recombinant zoster vaccine [RZV]) were selected, and their safety profiles were monitored at four tertiary hospitals and 10 primary care clinics. The response rates of the questionnaires on post-vaccination days 1, 7, 28, and 90 were 99.2%, 93.6%, 81.0%, and 48.7%, respectively. Of 555 AESI identified over 10 months, 10 cases received one of the selected non-NIP vaccines within 90 days of the event. CONCLUSION: We are establishing the first safety monitoring system for selected non-NIP vaccines in Korea since September 2022 and report its progress as of July 2023. However, continuous government support is essential for its maintenance and improvement.

Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: implications of immune imprinting and interference.

OBJECTIVES: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination. METHODS: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay. RESULTS: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups. DISCUSSION: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains.

Effectiveness of Bivalent mRNA Booster Vaccine Against COVID-19 in Korea.

BACKGROUND: Bivalent booster mRNA vaccines containing the omicron-variant strains have been introduced worldwide in the autumn of 2022. Nevertheless, the omicron subvariants evoked another large coronavirus disease 2019 (COVID-19) pandemic wave in late 2022 and early 2023. METHODS: A retrospective, test-negative, case-control study was conducted to estimate the vaccine effectiveness (VE) of bivalent COVID-19 vaccines in 8 university hospitals between January and February 2023. The case and control groups were divided based on nasopharyngeal COVID-19 real-time polymerase chain reaction results and matched based on age, sex, hospital, and date (week) of the test performed. The VE of the BA.1- or BA.4/BA.5-based mRNA vaccines were estimated. VE was calculated using the 1-adjusted odds ratio from multivariable logistic regression. RESULTS: In total, 949 patients and 947 controls were enrolled in this study. VE for the BA.4/BA.5-based bivalent mRNA vaccine was 43% (95% confidence interval [CI], 17, 61%). In subgroup analysis based on age and underlying medical conditions, BA.4/BA.5-based bivalent mRNA vaccine was effective against old adults aged ≥ 65-years (VE, 55%; 95% CI, 23, 73%) and individuals with comorbidities (VE, 54%; 95% CI, 23, 73%). In comparison, the BA.1-based bivalent mRNA vaccine did not demonstrate statistically significant effectiveness (VE, 25%; 95% CI, -8, 49%). CONCLUSION: The BA.4/BA.5-based bivalent mRNA booster vaccine provided significant protection against COVID-19 in the Korean adults, especially in the older adults aged ≥ 65 years and in individuals with underlying medical conditions.

Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis.

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.

Cost-effectiveness of high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccine for older people in a country with high influenza vaccination rate.

The highdose quadrivalent influenza vaccine (QIVHD) has shown improved protection against influenza and its complications in older adults. We aimed to evaluate the costeffectiveness of QIVHD compared with QIVSD among Korean adults aged ≥ 65 years in reducing influenzarelated disease burden. We evaluated the 2016/2017 and 2017/2018 seasons and their average values using a static decision tree model. The difference in efficacy between standard-dose (SD) and high-dose (HD) was calculated based on the results of a clinical trial comparing Fluzone® High-Dose Vaccine and Fluzone® Vaccine in older adults. Incremental cost-effectiveness ratios (ICERs) were assessed from the healthcare system perspective. A discount rate of 4.5% was applied to life-year-gained (LYG) values and utilities. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economic sources of uncertainty. In the analysis of the 2017/2018 season, the QIV-HD strategy generated an excess of 0.00182 life-years (Lys)/person and 0.003953 quality-adjusted life-years (QALYs)/person compared with QIV-SD. The ICER was 6,467.56 United States Dollars (USD)/QALY. In the analysis from the 2016/2017 season, QIV-HD caused a surplus of 0.00117 Lys/person and 0.003272 QALYs/person compared with QIV-SD. ICER was 7,902.46 USD /QALY. From the average data of the 2016/2017 and 2017/2018 seasons, an excess of 0.00147 Lys/person and 0.003561 QALYs/person were generated using QIV-HD compared with QIV-SD, while the ICER was 7,190.44 USD /QALY. From the healthcare system perspective, QIV-HD was a more cost-effective vaccination option in reducing influenza-related disease burden and healthcare costs in Koreans aged ≥ 65 years compared with QIV-SD.

Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

Metformin reduces the risk of developing influenza A virus related cardiovascular disease.

This study investigated the drug repositioning potential of metformin for cardiovascular risk due to influenza A virus infection. Statistical analysis was performed to analyze factors related to the risk of death after IAV infection in diabetic patients. Through in vitro and in vivo experiments, the effect of metformin on influenza A virus infection in non-diabetic conditions was analyzed. In logistic regression analysis, influenza vaccination (OR = 0.378, p-value = 0.007, 0.186 < 95% C·I < 0.768) and metformin treatment (OR = 0.380, p-value = 0.016, 0.173 < 95% C·I < 0.835) were associated with a decreased influenza-related mortality in diabetic patients. In vitro and in vivo studies showed that viral replication and influenza A virus-induced cytokine expression were inhibited by metformin. In particular, MCP-1 and IP-10, cytokines related to cell infiltration and cardiovascular disease development, were significantly reduced by metformin under influenza A virus infection condition. As a result, the acute exacerbation of atherosclerosis caused by influenza A virus in mouse aorta was inhibited by metformin. In addition, we found that regulation of AKT/MAPK signaling plays an important role in the mechanism of metformin. In conclusion, we demonstrated the potential and mechanism of metformin as a treatment for acute exacerbation of atherosclerosis caused by influenza A virus infection.

Assessment of Disease Burden and Immunization Rates for Vaccine-Preventable Diseases in People Living with HIV: The Korea HIV/AIDS Cohort Study.

BACKGROUND: Prophylactic immunization is important for human immunodeficiency virus (HIV)-infected patients; however, there are insufficient data on the burden of vaccine-preventable diseases (VPDs), vaccination rates, and factors influencing vaccination. MATERIALS AND METHODS: The incidence and prevalence of VPDs in HIV-infected patients between 2006 and 2017 were estimated using the Korean HIV/acquired immune deficiency syndrome (AIDS) cohort database. In addition, we evaluated the vaccination rates and influencing factors for vaccination in HIV-infected patients through multilevel analysis of clinico-epidemiological factors, immune status, and psychological status. A questionnaire survey was conducted among experts to determine whether they recommend vaccination for HIV-infected patients. RESULTS: The incidence rates of hepatitis B virus (HBV) infection, herpes zoster, and anogenital warts were 1.74, 7.38, and 10.85 per 1,000 person-years, respectively. The prevalence of HBV infection and anogenital warts at enrollment was 4.8% and 8.6%, respectively, which increased to 5.3% and 12.0%, respectively, by 2017. In HIV-infected patients, HBV (21.7% in 2008, 56.3% in 2013, and 75.4% in 2017) and pneumococcal vaccination rates (3.0% in 2015, 7.6% in 2016, and 9.6% in 2017) increased annually, whereas the influenza vaccination rate remained similar by season (32.7 - 35.6%). In the multilevel analysis, peak HIV viral load (≥50 copies/mL: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.44 - 0.93; reference, <50 copies/mL) was an influencing factor for pneumococcal vaccination, while nadir CD4 T-cell counts (200 - 350 cells/mm3: OR = 0.54, 95% CI: 0.38 - 0.76; <200 cells/mm3: OR = 0.89, 95% CI: 0.62 - 1.28; reference, ≥350 cells/mm3) was an influencing factor for HBV vaccination. Influenza vaccination was associated with male sex (OR = 1.94) and the number of antiretroviral therapy (ART) regimen change (OR = 1.16), but was not significantly associated with HIV viral load or CD4 T-cell counts. Most experts responded that they administer hepatitis A virus, HBV, pneumococcal, and influenza vaccines routinely, but not human papillomavirus (12.9%) or herpes zoster vaccines (27.1%). CONCLUSION: The burden of vaccine-preventable diseases was quite high in HIV-infected patients. Nadir CD4 T-cell counts, peak HIV viral loads, and the number of ART regimen change are significant factors related to vaccination. Considering the low vaccination rates for VPDs, there was a discordance between experts' opinions and real clinical practice in the medical field.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Neutralizing Activity against BQ.1.1, BN.1, and XBB.1 in Bivalent COVID-19 Vaccine Recipients: Comparison by the Types of Prior Infection and Vaccine Formulations.

Bivalent COVID-19 vaccines that contain BA.1 or BA.4/BA.5 have been introduced worldwide in response to pandemic waves of Omicron subvariants. This prospective cohort study was aimed to compare neutralizing antibodies (Nabs) against Omicron subvariants (BA.1, BA.5, BQ.1.1, BN.1, and XBB.1) before and 3-4 weeks after bivalent booster by the types of SARS-CoV-2 variants in prior infections and bivalent vaccine formulations. A total of 21 participants were included. Prior BA.1/BA.2-infected, and BA.5-infected participants showed significantly higher geometric mean titers of Nab compared to SARS-CoV-2-non-infected participants after bivalent booster (BA.1, 8156 vs. 4861 vs. 1636; BA.5, 6515 vs. 4861 vs. 915; BQ.1.1, 697 vs. 628 vs. 115; BN.1, 1402 vs. 1289 vs. 490; XBB.1, 434 vs. 355 vs. 144). When compared by bivalent vaccine formulations, Nab titers against studied subvariants after bivalent booster did not differ between BA.1 and BA.4/BA.5 bivalent vaccine (BA.1, 4886 vs. 5285; BA.5, 3320 vs. 4118; BQ.1.1, 311 vs. 572; BN.1, 1028 vs. 1095; XBB.1, 262 vs. 362). Both BA.1 and BA.4/BA.5 bivalent vaccines are immunogenic and provide enhanced neutralizing activities against Omicron subvariants. However, even after the bivalent booster, neutralizing activities against the later Omicron strains (BQ.1.1, BN.1, and XBB.1) would be insufficient to provide protection.

Herpes Zoster Reactivation After mRNA and Adenovirus-Vectored Coronavirus Disease 2019 Vaccination: Analysis of National Health Insurance Database.

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

Concurrent Subacute Thyroiditis and Graves' Disease After COVID-19: A Case Report.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves' disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Clinical implications of gut microbiota and cytokine responses in coronavirus disease prognosis.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut microbiome. We investigated whether the gut microbiome in the early stage of SARS-CoV-2 infection was associated with the prognosis of coronavirus disease (COVID-19). Methods: Thirty COVID-19 patients and 16 healthy controls were prospectively enrolled. Blood and stool samples and clinical details were collected on days 0 (enrollment), 7, 14, and 28. Participants were categorized into four groups by their clinical course. Results: Gut microbiota composition varied during the clinical course of COVID-19 and was closely associated with cytokine levels (p=0.003). A high abundance of the genus Dialister (linear discriminant analysis [LDA] effect size: 3.97856, p=0.004), species Peptoniphilus lacrimalis (LDA effect size: 4.00551, p=0.020), and Anaerococcus prevotii (LDA effect size: 4.00885, p=0.007) was associated with a good prognosis. Starch, sucrose, and galactose metabolism was highly activated in the gut microbiota of the poor prognosis group. Glucose-lowering diets, including whole grains, were positively correlated with a good prognosis. Conclusion: Gut microbiota may mediate the prognosis of COVID-19 by regulating cytokine responses and controlling glucose metabolism, which is implicated in the host immune response to SARS-CoV-2.

Incidence and Healthcare Burden of Pertussis among Older Adults with and without Pre-Existing Chronic Obstructive Pulmonary Disease or Asthma in South Korea.

A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-|6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.

COVID-19 Vaccination in Korea.

Since December 2020, various coronavirus disease 2019 (COVID-19) vaccines have been developed and approved. As of February 2023, mRNA vaccines including bivalent vaccines (Pfizer/BioNTech, Moderna), recombinant protein vaccines (Novavax, SK Bioscience), and viral vector vaccines (AstraZeneca, Janssen) have been approved in Korea. COVID-19 vaccination can effectively reduce hospitalization and deaths due to symptomatic COVID-19, especially severe and critical COVID-19. The primary series vaccination against COVID-19 is recommended for all adults aged ≥18 years in Korea. Booster vaccination with the bivalent mRNA vaccine is available for those ≥12 years who have completed the primary series vaccination, regardless of the type of vaccine previously received, and is recommended for all adults. Booster vaccination can be administered since 90 days after the last dose. Localized and systemic adverse events following COVID-19 vaccination are relatively common and more frequently documented in younger age groups. Rare but potentially serious specialized adverse reactions include anaphylaxis, thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré syndrome. Previous severe allergic reactions, such as anaphylaxis, to any COVID19 vaccine or vaccine component are considered a contraindication for vaccination. The indications and schedule for COVID-19 vaccination are subject to change based on further research results and the COVID-19 pandemic.