Estimates of Vaccine Effectiveness of the Updated Monovalent XBB.1.5 COVID-19 Vaccine Against Symptomatic SARS-CoV-2 Infection, Hospitalization, and Receipt of Oxygen Therapy in South Korea - October 26 to December 31, 2023.

OBJECTIVES: We evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. DESIGN: This study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26-December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. RESULTS: In total, 5,516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. CONCLUSIONS: The short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

A Case Report of Lenacapavir Use in a Patient with Multidrug-Resistant HIV: The First Experience in Asia.

Lenacapavir is a novel, first-in-class, capsid inhibitor, which has been approved as an adjunctive therapy for multidrug-resistant human immunodeficiency virus (HIV)-1 virus in combination with optimized background regimen (OBR). Lenacapavir has demonstrated a significant decrease in viral load and high rate of virologic suppression in patients with multidrug-resistant HIV-1 infection with limited treatment options. Here, we report a case of 43-year-old male who was diagnosed with HIV-1 infection in 2005 but failed to achieve viral suppression due to multiclass resistance. After lenacapavir use with OBR, viral suppression was achieved, and recovery of CD4+ T-cell count was observed for 8 months. This case report shows the first lenacapavir experience in Asia in a heavily treatment-experienced HIV patient with limited treatment options.

Antiretroviral Therapy during Long-term Surgical Care: 'Exploring Difficult Cases in HIV Clinics' of the Korean Society for AIDS Conference in 2023.

With advancements in antiretroviral therapy (ART), the average lifespan of people with human immunodeficiency virus (HIV) is increasing, as is the number of older adults with HIV. Accordingly, the number of patients with HIV who undergo surgery or require critical care for various reasons is increasing. Since the prognosis of people with HIV depends on the continuous and effective maintenance of ART, there is a need to consider effectively maintaining ART in people with HIV in these conditions. This case involved a 55-year-old patient with well-controlled HIV who received ART and presented to the emergency room with acute abdominal pain. He was diagnosed with extensive bowel infarction and panperitonitis and received critical care in the intensive care unit, including mechanical ventilation and continuous renal replacement therapy. The patient was administered enteral nutrition via a nasogastric tube. The patient subsequently underwent extensive small bowel resection and developed short bowel syndrome. The patient maintained ART during that period. A literature review related to the use of ART under these conditions is included in this study. This case was discussed at the [Exploring Difficult Cases in HIV Clinics] of the Korean Society for AIDS Conference held in 2023.

Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

Development of a Plasmodium vivax malaria model for evaluating the effects of control strategies on the malaria burden in Democratic People's Republic of Korea.

Background: Plasmodium vivax malaria has been one of the most troublesome diseases in the Democratic People's Republic of Korea (DPRK). Given that a majority of malaria cases are concentrated near the demilitarized zone, concerted elimination efforts from both the Republic of Korea (ROK) and DPRK are essential for a malaria-free Korean Peninsula. This study assessed the impact of rapid diagnostic tests (RDTs) and tafenoquine on malaria incidence in DPRK. Methods: We patterned the current model structure from the previously developed Plasmodium vivax malaria dynamic transmission model for ROK. Model parameters were adjusted using demographic and climate data from malaria-risk areas in DPRK, and the model was calibrated to annual malaria incidences from 2014 to 2018 in DPRK, as reported by the World Health Organization. Subsequently, we estimated the preventable malaria cases over a decade after introducing RDTs and tafenoquine compared to using microscopy alone and primaquine, respectively. Sensitivity analysis was performed to account for uncertainty in model parameters. Results: When comparing RDTs to microscopy, a one-day reduction in diagnostic time due to the introduction of RDTs led to a reduction in malaria incidence by 26,235 cases (65.6%) over the next decade. With a two-day reduction, incidences decreased by 33,635 (84.1%). When comparing a single dose of tafenoquine with a 14-day primaquine regimen, the former prevented 1,222 (77.5%) relapse cases and 4,530 (11.3%) total cases over the years. Conclusion: The continuous and simultaneous implementation of RDTs and tafenoquine emerges as a potent strategy to considerably reduce malaria in DPRK.

Influence of contrast medium on long-term renal function and outcomes in patients with septic acute kidney injury: A propensity-matched cohort study.

PURPOSE: To investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI). MATERIALS AND METHODS: We performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days. RESULTS: During the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99). CONCLUSIONS: The administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.

A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations.

BACKGROUND: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies. METHOD: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring. RESULTS: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group (P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions (P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects. CONCLUSION: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).

Post-Diagnosis HCV RNA Testing Rates Prior to HCV Treatment Among People Living With HIV With HCV Antibody Positivity in the Asia-Pacific Region.

HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post-diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia-Pacific region. PLHIV with positive HCV antibody and in follow-up after 2010 were included. Patients were considered HCV-antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post-diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person-years. Factors associated with increased testing rates included later calendar years of follow-up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow-up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower-cost point of care assays, will be required to achieve elimination of HCV as a public health issue.

HIV treatment outcomes after 10 years on ART in the TREAT Asia Observational Database (TAHOD) and Australian HIV Observational Database (AHOD).

BACKGROUND: Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TAHOD) and Australia (AHOD). METHODS: People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analysed using repeated measure linear regression. Survival after 10 years was analysed using competing risk regression. RESULTS: There were 7139 people included: 4867 (68%) from TAHOD and 2272 (32%) from AHOD. Higher CD4 after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101-200: difference=35, 95%CI 18, 51; >200: difference=125, 95%CI 107, 142) compared to ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL which subsequently decreased to <500 (difference=225, 95%CI 213, 236); or those who achieved and maintained CD4 ≥500 cells/µL (difference=402, 95%CI 384, 420), compared to always <500 in the previous decade. Prior protease inhibitor (PI) -based regimen (difference=-17, 95%CI -33, -1) compared to no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = -38, 95%CI -62, -15; and difference=-44, 95%CI -61, -27, respectively) compared to no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (sub-hazard ratio=1.34, 95%CI 1.04, 1.71). CONCLUSIONS: Sustaining high CD4 levels and minimising TI has far-reaching benefits well beyond the first decade of ART.

Outcomes of hematopoietic stem cell transplantation in patients with SARS-CoV-2 infection during the Omicron era.

Here, we present the outcomes of four patients with COVID-19 who underwent hematopoietic stem cell transplantation (HSCT) at the National Cancer Center in South Korea. Despite concerns about the unfavorable course of COVID-19 in HSCT recipients, none of our patients experienced severe COVID-19. Moreover, extended viral shedding in case 1, lasting over 100 days, was resolved after successful engraftment. Contracting the virus when the host could not mount enough of an immune reaction might result in a paradoxically favorable course. Vaccination, monoclonal antibodies, and antiviral agent usage against COVID-19 might also be effective. We suggest, if necessary, HSCT should not be deferred in COVID-19 patients.

Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific region.

INTRODUCTION: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific. METHODS: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression. RESULTS: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/µL and 162 (78.6%) had CD4 ≤100 cells/µL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/µL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/µL: OR 0.14, 95% CI 0.06-0.34; >200 cells/µL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/µL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis. CONCLUSIONS: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH.

Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in treatment-naïve and treatment-experienced people with HIV: Findings from the Asia cohort of the BICSTaR study.

BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort. METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group). RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/µl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/µl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328). CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.

Hepatitis B Reactivation and Vaccination Effectiveness after Solid Organ Transplantation: A Matched Case-Control Study.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(-) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Comparison of HIV characteristics across 3 datasets: the Korea HIV/AIDS Cohort Study prospective, retrospective, and national reporting system.

OBJECTIVES: The Korea HIV/AIDS Cohort Study has been conducted prospectively for 18 years. However, it faces limitations in representing the entire population of patients with human immunodeficiency virus (HIV) in Korea. To address these limitations and validate the study design, we analyzed characteristics across several HIV datasets. METHODS: We compared epidemiological and clinical characteristics from 3 datasets: the Korea HIV/AIDS Cohort Study (dataset 1, n=1,562), retrospective cohort data (dataset 2, n=2,665), and the national HIV reporting system of the Korea Disease Control and Prevention Agency (KDCA) (dataset 3, n=17,403). RESULTS: The demographic characteristics of age, sex, and age at HIV diagnosis did not differ significantly across datasets. However, dataset 3 contained a higher proportion of patients diagnosed after 2008 (69.5%) than the other datasets. Regarding transmission routes, same-sex contact accounted for a greater proportion of dataset 1 (59.8%) compared to datasets 2 (20.9%) and 3 (32.6%). The proportion of patients with CD4 T-cell counts below 200/mm3 at HIV diagnosis was higher in datasets 1 (39.4%) and 2 (33.3%) compared to dataset 3 (16.3%). Initial HIV viral load measurements were not obtained for dataset 3. CONCLUSIONS: The Korea HIV/AIDS Cohort Study demonstrated representativeness regarding the demographic characteristics of Korean patients. Of the sources, dataset 1 contained the most data on transmission routes. While the KDCA data encompassed all HIV patients, it lacked detailed clinical information. To improve the representativeness of the Korea HIV/AIDS Cohort Study, we propose expanding and revising the cohort design and enrolling more patients who have been recently diagnosed.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.