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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.
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Anticancer chemo-immunotherapy has gained considerable attention across various scientific domains as a prospective approach for the comprehensive eradication of malignant tumors. Recent research has particularly been focused on traditional anthracycline chemo drugs, such as doxorubicin and mitoxantrone. These compounds trigger apoptosis in tumor cells and evoke immunogenic cell death (ICD). ICD is a pivotal initiator of the cancer-immunity cycle by facilitating the release of damage-associated molecular patterns (DAMPs). The resultant DAMPs released from cancer cells effectively activate the immune system, resulting in an increase in tumor-infiltrating T cells. In this study, we have innovated a co-delivery strategy involving folate-modified liposomes to deliver doxorubicin and monophosphoryl lipid A (MPLA) simultaneously to tumor tissue. The engineered liposomes exploit the overexpression of folate receptors within the tumor tissues. Delivered doxorubicin initiates ICD at the tumor cells, further enhancing the immunogenic stimulus. Additionally, MPLA helps T cell priming by activating antigen-presenting cells. This intricate interplay culminates in a synergistic effect, ultimately resulting in an augmented and potentiated anticancer chemo-immunotherapeutic liposomal treatment.
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Doxorrubicina , Muerte Celular Inmunogénica , Inmunoterapia , Lípido A , Liposomas , Receptor Toll-Like 4 , Liposomas/química , Doxorrubicina/farmacología , Doxorrubicina/química , Animales , Muerte Celular Inmunogénica/efectos de los fármacos , Humanos , Receptor Toll-Like 4/agonistas , Receptor Toll-Like 4/metabolismo , Ratones , Lípido A/análogos & derivados , Lípido A/química , Lípido A/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Línea Celular Tumoral , Femenino , Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Fólico/químicaRESUMEN
BACKGROUND: As the group at high risk for sepsis is increasing with the aging of the population, physical activity (PA), which has beneficial effects on various diseases, needs to be considered as a personalized prevention strategy for sepsis without direct anti-sepsis drug. PURPOSE: To examine the association between the amount of PA (based on intensity, duration, and frequency) and the incidence rates of sepsis and mortality after sepsis. METHODS: This was a large-scale, retrospective, longitudinal cohort study using data from the Korean National Health Insurance Service and the biennial general health screening program. The amount of PA self-reported at the time of the health screening was categorized as non-PA, mild (<500 metabolic equivalents [METs]-Min/Week), moderate (500-1000), severe (1000-1500), and extreme (≥1500). The multivariable regression model was adjusted for age, sex, income, body mass index, smoking, alcohol consumption, diabetes, hypertension, dyslipidemia, and chronic diseases. RESULTS: From 4,234,415 individuals who underwent a health screening in 2009, 3,929,165 subjects were selected after exclusion for wash-out period and a 1-year lag period, and then observed for the event of sepsis or all-cause death until December 2020. During a median 10.3 years of follow-up, 83,011 incidents of sepsis were detected. The moderate-PA group showed the lowest incidence (1.56/1000 person-years) and risk for sepsis, with an adjusted hazard ratio (aHR) of 0.73 (95% CI, 0.72-0.75, P < 0.001) compared with the non-PA group. The occurrence of sepsis among people aged ≥65 years and ex-smokers were significantly lower in the moderate-PA group (aHR; 0.77, 95% CI; 0.74-0.79; and 0.68, 0.64-0.71, respectively, Ps < 0.001). The long-term all-cause mortality after sepsis was significantly lower in the PA group than in the non-PA group (overall P = 0.003). CONCLUSIONS: Physical activity is associated with a lower risk of sepsis, especially in elderly people who have the highest incidence of sepsis. The protective effects of aerobic PA on sepsis might need to be incorporated with other interventions in sepsis guidelines through the accumulation of future studies.
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Ejercicio Físico , Sepsis , Humanos , Sepsis/epidemiología , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Estudios Retrospectivos , República de Corea/epidemiología , Anciano , Estudios Longitudinales , Adulto , Factores de RiesgoRESUMEN
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.
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Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Infección Irruptiva , ChAdOx1 nCoV-19/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Citocinas/sangre , Personal de Salud , Estudios Prospectivos , República de Corea , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.
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Vacuna BNT162 , Linfocitos T CD8-positivos , Humanos , Infección Irruptiva , Epítopos de Linfocito T , PéptidosRESUMEN
BACKGROUND: This study was designed to determine changes in risk factors on the prognosis of patients during each period of the bloodstream infection (BSI) timeline. METHODS: Through an integrated study of multivariable regressions with machine learning techniques, the risk factors for mortality during each period of BSI were analyzed. RESULTS: A total of 302,303 inpatients who underwent blood cultures during 2011-2021 were enrolled. More than 8 % of BSI cases progressed to subsequent BSI, and risk factors were identified as gut colonization with vancomycin-resistant enterococci (aOR 1.82; 95 % CI 1.47-2.24), intensive care unit admission (aOR 3.37; 95 % CI 3.35-4.28), and current cancer chemotherapy (aOR 1.54; 95 % CI 1.36-1.74). The mean SOFA score of the deceased patients during the first 7 days was 10.6 (SD 4.3), which was significantly higher than those on days 8-30 (7.0 ± 4.2) and after Day 30 (4.0 ± 3.5). BSIs caused by Acinetobacter baumannii and Candida albicans were more likely to result in deaths of patients for all time periods (all, P < 0.001). BSIs caused by Enterococcus faecalis and Enterococcus faecium were associated with a poor outcome in the period after Day 30 (both, P < 0.001). Nonsusceptible phenotypes to ß-lactam/ß-lactamase inhibitors of Escherichia coli and Klebsiella pneumoniae influenced the prognoses of patients with BSI in terms of high mortality rates during both days 8-30 and after Day 30. CONCLUSION: Influence of microbiological factors on mortality, including BSI-causative microorganisms and their major antimicrobial resistance, was emphasized in both periods of days 8-30 and after Day 30.
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Bacteriemia , Sepsis , Enterococos Resistentes a la Vancomicina , Humanos , Bacteriemia/microbiología , Estudios Retrospectivos , Sepsis/complicaciones , Factores de Riesgo , Escherichia coliRESUMEN
Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.
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COVID-19 , SARS-CoV-2 , Humanos , Pruebas de Neutralización , SARS-CoV-2/genética , COVID-19/diagnóstico , Inmunoensayo , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
PURPOSE: We aimed to explore the clinical characteristics of Campylobacter bacteraemia and identify the trends, risk factors for mortality, and antimicrobial susceptibility patterns from clinical samples. METHODS: This retrospective cohort study included patients confirmed to have Campylobacter bacteraemia from seven hospitals between January 2010 and June 2021. Data on demographics and underlying history, clinical manifestation, and antimicrobial susceptibility patterns were collected and analyzed. Annual cases of Campylobacter enteritis were extracted from a public database. RESULTS: A total of 108 patients were included, and five species were isolated. Campylobacter jejuni accounted for 54 (50.0%) cases and 17 (16%) patients had no symptoms other than fever. In-hospital mortality occurred in 14 (13.0%) patients. C. jejuni bacteraemia was associated with lower mortality compared to non-C. jejuni bacteraemia. Underlying cancer and septic shock were the significant factors associated with in-hospital mortality. Quinolone resistance was high (59%), whereas only 4% of isolates exhibited macrolide resistance. There has been a significant increase in the number of Campylobacter enteritis cases, which was strongly correlated with the number of Campylobacter bacteraemia cases (Pearson's coefficient: 0.953; p < 0.0001). CONCLUSION: The notably increasing incidence of Campylobacter bacteraemia and antibiotic resistance patterns can challenge the treatment, necessitating collective efforts of national surveillance and networks by many departments.
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BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are global concerns in infection control, and the number of CPE outbreaks in hospitals is increasing despite the strengthening of contact precautions. This study aimed to confirm the prevalence and transition rate of CPE infection from stool surveillance culture and to identify the acquisition pathway of CPE. METHODS: This is a longitudinal review of patients with stool surveillance cultures at a tertiary center in Seoul, South Korea, from July 2018 to June 2020. Pulsed-field gel electrophoresis, multi-locus sequence typing, and whole genome sequencing were performed for carbapenemase-producing Klebsiella pneumoniae and Escherichia coli strains. RESULTS: Among 1620 patients who had undergone stool CPE surveillance cultures, only 7.1% of active surveillance at the Emergency Room (ER) and 4.4% of universal surveillance in the Intensive Care Unit (ICU) were stool CPE positive. The transition rates from stool carriers to clinical CPE infections were 29.4% in the ER and 31.3% in the ICU. However, it was significantly high (55.0%) in the initial stool CPE-negative ICU patients. Among the initial stool CPE-positive patients, hypertension (61% vs. 92.3%, P = 0.004), malignancy (28.8% vs. 53.8%, P = 0.027), and mechanical ventilation (25.4% vs. 53.8%, P = 0.011) were significant risk factors for clinical CPE infection. Molecular typing revealed that sequence type (ST) 307 and ST 395 were dominant in K. pneumoniae, and ST 410 was dominant in E. coli isolates. CONCLUSIONS: Active surveillance showed a higher detection rate than universal stool CPE screening, and one-third of positive stool CPE specimens ultimately developed subsquent clinical CPE infection. According to the molecular typing of the identified CPE strains, in-hospital spread prevailed over external inflow, and the transition rate to clinical CPE was particularly high in the ICU. Therefore, in order to control CPE propagation, not only active surveillance to block inflow from outside, but also continuous ICU monitoring within the hospital is necessary.
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Enfermedades Transmisibles , Infecciones por Enterobacteriaceae , Humanos , Escherichia coli/genética , Tipificación de Secuencias Multilocus , Prevalencia , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Klebsiella pneumoniae , Factores de Riesgo , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/diagnósticoRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.
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Infecciones por VIH , Leucoencefalopatía Multifocal Progresiva , Humanos , Infecciones por VIH/complicaciones , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Estudios Retrospectivos , Pronóstico , Terapia Antirretroviral Altamente Activa , InmunosupresoresRESUMEN
BACKGROUND: Trichosporon is an emerging yeast that causes invasive infections in immunocompromised patients experiencing prolonged hospitalisation, indwelling venous catheters and neutropenia. METHODS: This retrospective observational cohort study analysed invasive Trichosporon infections (ITIs) occurring between January 2005 and December 2022 at three tertiary hospitals and compared the clinical characteristics and prognostic factors of ITIs caused by Trichosporon asahii and non-T. asahii spp. After evaluating 1067 clinical isolates, we identified 46 patients with proven ITIs, defined as cases in which Trichosporon was isolated from blood, cerebrospinal fluid, or sterile tissues. RESULTS: The patients were separated into T. asahii and non-T. asahii groups containing 25 and 21 patients, respectively, all of which except one were immunocompromised. During this period, both the number of clinical isolates and patients with ITIs (mainly T. asahii) increased; whereas, cases involving non-T. asahii spp. decreased. Compared with the non-T. asahii group, the T. asahii group had more patients with multiple catheters (84% vs. 33%, p = .001) and those receiving renal replacement therapy (48% vs. 14%, p = .005). The all-cause 28-day mortality rate after ITI in the T. asahii group (44%) was significantly higher than in the non-T. asahii group (10%, Log-rank p = .014). The multivariate Cox regression model revealed that T. asahii (reference, non-T. asahii spp.; aHR = 4.3; 95% CI = 1.2-15.2, p = .024) and neutropenia for 5 days or more (aHR = 2.2, 95% CI = 1.5-3.6, p = .035) were independent factors in the 28-day mortality after ITI. CONCLUSION: The proven ITIs due to T. asahii produced more unfavourable outcomes compared with ITIs caused by non-T. asahii spp.
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Neutropenia , Trichosporon , Tricosporonosis , Humanos , Tricosporonosis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Estudios Retrospectivos , Neutropenia/tratamiento farmacológicoRESUMEN
Background: Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Methods: Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. Results: A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Conclusions: Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.
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BACKGROUND: Recent studies disputed the effectiveness of efforts to comply with contact precautions and isolation (CPI) considering relatively low intra-hospital transmission rate of healthcare facility-associated Clostridioides difficile infection (HCFA-CDI). We evaluated the potential causal effect of CPI on HCFA-CDI occurrence by comparing the incidence rate (IR) for different time periods with and without CPI implementation. METHODS: Long-term observational time-series data were separated into three periods (pre-CPI: January 2012-March 2016, CPI: April 2016-April 2021, post-CPI: May 2021-December 2022). CPI was suspended owing to the restriction of isolation rooms during the COVID-19 pandemic. We inferred potential causal outcomes by comparing predicted and observed IRs of HCFA-CDI using interrupted time-series analyses, including the Bayesian structural time-series or autoregressive integrated moving average (ARIMA) model in the R-language or SAS software. RESULTS: The monthly observed IR (44.9/100,000 inpatient-days) during the CPI period was significantly lower than the predicted IR (90.8) (-50.6% relative effect, P = 0.001). However, the observed IR (52.3) during the post-CPI period was significantly higher than the predicted IR (39.1) (33.6%, P = 0.001). The HCFA-CDI IR decreased during CPI (-14.3, P < 0.001) and increased post-CPI (5.4, P < 0.001) in the multivariable ARIMA model, which controlled for antibiotic usage, handwashing with soap and water, and number of toxin tests. CONCLUSIONS: Various time-series models revealed that CPI implementation had a potential causal effect on the reduction of HCFA-CDI incidence.
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COVID-19 , Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Humanos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Teorema de Bayes , Pandemias , COVID-19/epidemiología , COVID-19/prevención & control , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/prevención & controlRESUMEN
This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6-125.0) vs. 51.0 (17.9-122.3), p = 0.024), 2-3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5-926.5) vs. 555.0 (287.3-926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5-655.3) vs. 176.0 (94.3-255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.
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Helicobacter pylori is the primary causative agent of gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and peripheral B-cell lymphoma. H. pylori eradication often fails due to elevated antibiotic resistance. However, no previous studies have thoroughly examined amoxicillin resistance. Here, the objective was to identify clinical strains of H. pylori with amoxicillin resistance and to analyze single-nucleotide polymorphisms (SNPs) associated with amoxicillin resistance. From March 2015 to June 2019, genotypic and phenotypic amoxicillin resistance was analyzed using an E-test and whole-genome sequencing (WGS). Analysis of 368 clinical strains confirmed amoxicillin resistance in 31 strains (resistance rate of 8.7%). The genomes were extracted from nine resistant (<0.125 mg/L) strains, and WGS was performed for genetic analysis. WGS analysis identified SNPs present in pbp1a, pbp2, nhaC, hofH, hofC, and hefC in all nine isolates. Some of these genes may be related to amoxicillin resistance. A total of six SNPs (A69V, V374L, S414R, T503I, A592D, and R435Q) were identified in PBP2 of H-8, the most resistant strain. We predict that these six SNPs are associated with high amoxicillin resistance. Amoxicillin resistance should be considered in the clinical setting for the treatment failure of H. pylori eradication.
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C-reactive protein (CRP) or procalcitonin (PCT) alone has limitations in the early detection of infection or inflammation due to shortcomings in specificity and varied cut-off values. Recently, interleukin (IL)-6 has been assessed, but it is not known to what extent the three values are homogeneous in reality. This retrospective study was conducted with two large datasets (discrepancy set with results within 24 h of admission [7149 patients] and follow-up set until 2 weeks of hospital stay [5261 tests]) consisting of simultaneous examinations of CRP, PCT, and IL-6 between January 2015 and August 2021. The specific discrepant group (n = 102, 1.4%) with normal CRP (<10 mg/L) and PCT (<0.1 ng/mL) and high IL-6 (≥100 pg/mL) values was extracted from the discrepancy set. Dimensionality reduction and visualization were performed using Python. The three markers were not clearly clustered after t-distributed stochastic neighbor embedding. Pearson's correlation coefficients between two markers were substantially low (0.23−0.55). Among the high normalized IL-6 levels (≥0.5) (n = 349), 17.8% and 38.7% of CRP and PCT levels were very low (≤0.01). 9.2% and 13.4% of normal CRP (n = 1522) had high PCT (≥0.5 ng/mL) and IL-6 (≥100 pg/mL) values, respectively. Infection and bacteremia among 102 patients occurred in 36 (35.3%) and 9 (8.8%) patients, respectively. In patients with bacteremia, IL-6 was the first to increase, followed by PCT and CRP. Our study revealed that CRP, PCT, and IL-6 levels were considerably discrepant, which could be misinterpreted if only CRP tests are performed.
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Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted from July 2020 to July 2022 at a tertiary hospital in Korea. Those who were followed up for more than 12 months were included. We analyzed the baseline characteristics, effectiveness, resistant profiles, body weights, metabolic parameters, and safety of DTG/3TC treatment in 151 PLWH, dividing them into the treatment-naïve group and the switching group. The median DTG/3TC treatment durations in the treatment-naïve and switching groups were 507.5 and 525.0 days. In the treatment-naïve group, the viral RNA titer was undetectable at 6 and 12 months in 95% of patients. In the switching group, virologic suppression was well-maintained. Meanwhile, the creatinine levels were slightly elevated in both groups compared to baseline. Five participants complained of mild side effects, such as indigestion, constipation, diarrhea, and fatigue. However, no patient stopped treatment during the follow-up period. Since there was no virological failure or serious complications observed in this study, DTG/3TC may be a good treatment option for PLWH in Korea.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adulto , Humanos , Lamivudine/efectos adversos , Fármacos Anti-VIH/efectos adversos , Estudios Retrospectivos , Infecciones por VIH/tratamiento farmacológico , República de CoreaRESUMEN
PURPOSE: The association between reactogenicity and immunogenicity of the ChAdOx1 nCOV-19 is controversial. We aimed to evaluate this association among South Korean healthcare workers (HCWs). MATERIALS AND METHODS: Participants received two doses of the ChAdOx1vaccine 12 weeks apart. Blood samples were tested for anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike protein receptor binding domain antibodies about 2 months after the first and second doses using the Elecsys Anti-SARS-CoV-2 S assay kits. Adverse events were noted using an online self-reporting questionnaire. RESULTS: Among the 232 HCWs, pain (85.78% after the first dose vs. 58.62% after the second dose, p<0.001) was the most prominent local reaction, and myalgia or fatigue (84.05% vs. 53.02%, p<0.001) was the most prominent systemic reaction. The frequency of all adverse events was significantly reduced after the second dose. After the first dose, the anti-SARS-CoV-2 S showed significantly higher titer in the group with swelling, itching, fever, and nausea. Also, the anti-SARS-CoV-2 S titer significantly increased as the grade of fever (p=0.007) and duration of fever (p=0.026) increased; however, there was no significant correlation between immunogenicity and adverse event after the second dose. The group with pain after the first dose showed a greater increase in the anti-SARS-CoV-2 S difference between the second and first doses compared to the group without pain (542.2 U/mL vs. 363.8 U/mL, p=0.037). CONCLUSION: The frequency of adverse events occurring after the first dose of the ChAdOx1 was significantly reduced after the second dose. Interestingly, the elevation of anti-SARS-CoV-2 S titer was significantly increased in the group with pain after the first dose.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , COVID-19/prevención & control , SARS-CoV-2 , Personal de Salud , Fiebre , Dolor/etiología , Anticuerpos , República de CoreaRESUMEN
Estimating neutralizing activity in vaccinees is crucial for predicting the protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the plaque reduction neutralization test (PRNT) requires a biosafety level 3 facility, it would be advantageous if surrogate virus neutralization test (sVNT) assays and binding assays could predict neutralizing activity. Here, five different assays were evaluated with respect to the PRNT in vaccinees: three sVNT assays from GenScript, Boditech Med, and SD Biosensor and two semiquantitative binding assays from Roche and Abbott. The vaccinees were subjected to three vaccination protocols: homologous ChAdOx1, homologous BNT162b2, and heterologous administration. The ability to predict a 50% neutralizing dose (ND50) of ≥20 largely varied among the assays, with the binding assays showing substantial agreement (kappa, ~0.90) and the sVNT assays showing relatively poor performance, especially in the ChAdOx1 group (kappa, 0.33 to 0.97). The ability to predict an ND50 value of ≥118.25, indicating a protective effect, was comparable among different assays. Applying optimal cutoffs based on Youden's index, the kappa agreements were greater than 0.60 for all assays in the total group. Overall, relatively poor performance was demonstrated in the ChAdOx1 group, owing to low antibody titers. Although there were intra-assay differences related to the vaccination protocols, as well as interassay differences, all assays demonstrated fair performance in predicting the protective effect using the new cutoffs. This study demonstrates the need for a different cutoff for each assay to appropriately determine a higher neutralizing titer and suggests the clinical feasibility of using various assays for estimation of the protective effect. IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic continues to last, despite high COVID-19 vaccination rates. As many people experience breakthrough infection after prior infection and/or vaccination, estimating the neutralization activity and predicting the protective effect are major issues of concern. However, since standard neutralization tests are not available in most clinical laboratories, it would be beneficial if commercial assays could predict these aspects. In this study, we evaluated the performance of three sVNT assays and two semiquantitative binding assays targeting the receptor-binding domain with respect to the PRNT. Our results suggest that these assays could be used for predicting the protective effect by adjusting the cutoffs.
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COVID-19 , Vacunas , Humanos , SARS-CoV-2 , Pruebas de Neutralización , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19/prevención & control , Anticuerpos Antivirales , Anticuerpos NeutralizantesRESUMEN
Introduction: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy. Methods: We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant. Results: We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT). Conclusion: Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.