Fine-Scale Spatial Prediction on the Risk of Plasmodium vivax Infection in the Republic of Korea.

BACKGROUND: Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed. METHODS: The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019-2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB. CONCLUSION: Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.

Barriers against and strategies for malaria control during the COVID-19 pandemic in low- and middle-income countries: a systematic review.

BACKGROUND: The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported. Although it is crucial to systematically understand the main causes of the disruption to malaria control and synthesize strategies to prepare for future pandemics, such studies are scarce. Therefore, this study aims to better identify barriers against and strategies for malaria control. METHODS: Following the PRISMA guidelines and through searches of electronic databases and Google Scholar, a systematic literature review was conducted to identify studies pertaining to malaria control published between January 2020 and December 2021. Only studies that discussed reported barriers and/or strategies related to malaria were included for the review. The Mixed Methods Quality Appraisal Tool (MMAT) and the Authority, Accuracy, Coverage, Objectivity, Date and Significance (AACODS) checklist were used for quality appraisal. Key information such as literature type, study design, setting and population, interventions, outcomes, barriers, and strategies were extracted. With an existing framework of four dimensions (accessibility, affordability, availability, and acceptability) further subdivided by the supply and demand sides, this study synthesized information on barriers and strategies related to malaria control and further categorized the strategies based on the time frame. RESULTS: From the 30 selected studies, 27 barriers and 39 strategies were identified. The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control. The strategies were distinguished between short-term, for instant response, and mid to long-term for future readiness. CONCLUSIONS: The pandemic resulted in complex barriers to malaria control, particularly imposing a double burden on LMICs. Identifying strategies to overcome said barriers provides useful insights in the decision-making processes for the current and future pandemic. Cross-cutting strategies that integrate all dimensions need to be considered. Health system strengthening and resilience strategy appropriate for country-specific context is fundamental.

Trends, clinical characteristics, antimicrobial susceptibility patterns, and outcomes of Campylobacter bacteraemia: a multicentre retrospective study.

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.

Within-Host Evolution of SARS-CoV-2 in a B-Cell Depleted Patient With Successful Treatment.

Prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunocompromised host is a challenge as the treatment and infection control for chronic coronavirus disease 2019 infection is not well established and there is a potential risk of new variants emerging. A 48-year-old woman who underwent chemotherapy, including rituximab and steroid, had reactivation of SARS-CoV-2 68 days after the virus was first detected. She successfully recovered after receiving convalescent plasma and intravenous immunoglobulin. Genomic analysis demonstrated that viruses collected from the nasopharyngeal specimens at day 0 and day 68 had 18 different nucleotide mutations, implying within-host evolution after in-depth epidemiologic investigation.

Effects of early corticosteroid use in patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. METHODS: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. RESULTS: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. CONCLUSIONS: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Correction: Increasing Fusobacterium infections with Fusobacterium varium, an emerging pathogen.

[This corrects the article DOI: 10.1371/journal.pone.0266610.].

Late-Onset Granulomatous Pneumocystis jirovecii Pneumonia in A Renal Transplant Recipient: A Clinical Grand Round Conference Case in 2022.

Late-onset Pneumocystis jirovecii pneumonia (PCP) can be developed in solid organ transplant (SOT) patients. Granulomatous P. jirovecii pneumonia (GPCP) can occur in immunocompromised patients, but has rarely been reported in SOT recipients. The diagnosis of GPCP is difficult since the sensitivity of sputum and bronchoalveolar lavage is low and atypical patterns are shown. A 60-year-old man, who had undergone renal transplantation 24 years ago presented with nodular and patchy lung lesions. He was asymptomatic and stable. After empirical treatment with a fluoroquinolone, the condition partially resolved but relapsed 4 months later. The pulmonary nodule was resected, and GPCP was confirmed. The pathogenesis of GPCP remains unclear, but in SOT recipients presenting with an atypical lung pattern, GPCP should be considered. This case was discussed at the Grand Clinical Ground of the Korean Society of Infectious Disease conference on November 3, 2022.

Role of α-Defensin and the Microbiome in Prosthetic Joint Infection: A Prospective Cohort Study in Korea.

The utility of α-defensin (AD), leukocyte esterase (LE) levels, and metagenomics sequencing as diagnostic tools for prosthetic joint infection (PJI) has been suggested, but there are few studies among the Asian population. This study aimed to evaluate the diagnostic performance of various biomarkers for PJI and the role of the microbiome in the synovial fluid of patients with prostheses. Patients with suspected knee PJI were enrolled, and their blood and synovial fluid were collected. The cases were classified into the PJI and non-PJI groups. Significant differences between the two groups were observed in the levels of AD (4698 µg/L vs. 296 µg/L, p < 0.001) and positivity for LE (62.5% vs. 21.1%, p = 0.01). AD had 94.4% sensitivity and 89.5% specificity for diagnosing PJI, whereas LE had 37.5% sensitivity and 100% specificity. Microbiome taxonomic profiling showed high sensitivity. The number of operational taxonomic units and the richness of the microbiome in the synovial fluid were higher in the non-PJI than in the PJI group. AD has shown encouraging results in the Asian population as a diagnostic biomarker for PJI, and LE can be used as a diagnostic adjunct. The bacterial richness of the synovial fluid is likely associated with infections.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study.

PURPOSE: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. RESULTS: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. CONCLUSION: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

A heterologous AZD1222 priming and BNT162b2 boosting regimen more efficiently elicits neutralizing antibodies, but not memory T cells, than the homologous BNT162b2 regimen.

BACKGROUND: Comparative analyses of SARS-CoV-2-specific immune responses elicited by diverse prime-boost regimens are required to establish efficient regimens for the control of COVID-19. METHOD: In this prospective observational cohort study, spike-specific immunoglobulin G (IgG) and neutralizing antibodies (nAbs) alongside spike-specific T-cell responses in age-matched groups of homologous BNT162b2/BNT162b2 or AZD1222/AZD1222 vaccination, heterologous AZD1222/BNT162b2 vaccination, and prior wild-type SARS-CoV-2 infection/vaccination were evaluated. RESULTS: Peak immune responses were achieved after the second vaccine dose in the naïve vaccinated groups and after the first dose in the prior infection/vaccination group. Peak titers of anti-spike IgG and nAb were significantly higher in the AZD1222/BNT162b2 vaccination and prior infection/vaccination groups than in the BNT162b2/BNT162b2 or AZD1222/AZD1222 groups. However, the frequency of interferon-γ-producing CD4+ T cells was highest in the BNT162b2/BNT162b2 vaccination group. Similar results were observed in the analysis of polyfunctional T cells. When nAb and CD4+T-cell responses against the Delta variant were analyzed, the prior infection/vaccination group exhibited higher responses than the groups of other homologous or heterologous vaccination regimens. CONCLUSION: nAbs are efficiently elicited by heterologous AZD1222/BNT162b2 vaccination, as well as prior infection/vaccination, whereas spike-specific CD4+T-cell responses are efficiently elicited by homologous BNT162b2 vaccination. Variant-recognizing immunity is more efficiently generated by prior infection/vaccination than the other homologous or heterologous vaccination regimens.

Surveillance of Close Contacts and Implications of Pediatric Patients with COVID-19-Experiences from a Single Residential Treatment Center.

Residential treatment centers (RTCs) are successful in isolating and closely monitoring adults confirmed with coronavirus disease 2019 (COVID-19), but there are concerns for children who need care. This study was conducted as a retrospective analysis of the surveillance of guardians who entered an RTC with infected pediatric patients to identify the secondary attack rate of COVID-19 to close contacts in a single RTC and to provide directions for developing guidelines for caregivers who co-isolate with infected children. When caregivers were admitted to this RTC, aside from negative confirmation before discharge, tests were additionally performed one or two times. There were 57 index children and adolescent patients who entered the RTC with their parents as caregivers. The secondary attack rate by pediatric patients to close contacts outside their households was 25% (95% confidence interval, 10.0 to 40.0) (8 out of 32 contacts). The transmissibility of SARS-CoV-2 in children was close to zero at 6 days after the confirmation tests. It is reasonable to test the close contacts of pediatric patients after 7 days of isolation to identify infections among caregivers.

Increasing Fusobacterium infections with Fusobacterium varium, an emerging pathogen.

Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective study to investigate the clinical features of patients with Fusobacterium infections and the differences between infections caused by the species F. necrophorum, F. nucleatum, and F. varium. Additionally, we attempted to identify risk factors for Fusobacterium-associated mortality. This study included all patients at a large tertiary care teaching hospital in South Korea with Fusobacterium infections from January 2006 to April 2021. Demographic, clinical, laboratory, and outcome data were analyzed. Multiple logistic regression analysis was performed to assess the risk factors for in-hospital mortality associated with F. nucleatum and F. varium infections. We identified 272 patients with Fusobacterium infections during the study period. The number of Fusobacterium cases has increased recently, with F. varium infections markedly increasing since 2016 and causing a significant proportion of infections. Patients with F. varium infections were older and had a higher proportion of nosocomial infections than the other groups. The F. nucleatum and F. varium groups showed higher in-hospital mortality than the F. necrophorum group. Through logistic regression analysis, APACHE II score and serum albumin level were considered risk factors for in-hospital mortality. APACHE II score was positively correlated with age, red cell distribution width, and serum blood urea nitrogen, and negatively correlated with serum albumin level. Infections caused by Fusobacterium species are increasing. F. varium causes a significant proportion of severe infections.

Clinical and microbiological characteristics of and risk factors for bloodstream infections among patients with extracorporeal membrane oxygenation: a single-center retrospective cohort study.

Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. This single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of > 48 h for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. A total of 480 patients underwent ECMO for cardiogenic shock (n = 267, 55.6%) or respiratory failure (n = 213, 44.4%) during the study period. The incidence was 20.0 episodes per 1000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n = 24), followed by vancomycin-resistant Enterococcus (n = 21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio [OR] 2.647, p < 0.001), veno-arterial-venous mode (OR 1.911, p = 0.030), and total ECMO duration (OR 1.030, p = 0.007) were significant risk factors for bacteremia. The total ECMO duration was the only risk factor associated with candidemia (OR 1.035, p = 0.010). The mortality rate was significantly higher in the bacteremia (57.7%) and candidemia (69.2%) groups than that in the non-BSI group (43.6%). BSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents.

Impact of Valve Culture Positivity on Prognosis in Patients with Infective Endocarditis Who Underwent Valve Surgery.

INTRODUCTION: Infective endocarditis (IE) is a severe and fatal infection with high in-hospital and overall mortality rates of approximately up to 30%. Valve culture positivity was associated with in-hospital mortality and postoperative complications; however, few studies have analyzed the relationship between valve cultures and overall mortality over a long observation period. This study aimed to compare the association of valve culture positivity with overall mortality in patients with IE who underwent valve surgery. METHODS: A total of 416 IE patients admitted to a tertiary hospital in South Korea from November 2005 to August 2017 were retrospectively reviewed. A total of 202 IE patients who underwent valve surgery and valve culture were enrolled. The primary endpoint was long-term overall mortality. Kaplan-Meier curve and Cox proportional hazards model were used for survival analysis. RESULTS: The median follow-up duration was 63 (interquartile range, 38-104) months. Valve cultures were positive in 22 (10.9%) patients. The overall mortality rate was 15.8% (32/202) and was significantly higher in valve culture-positive patients (36.4%, p = 0.011). Positive valve culture [hazard ratio (HR) 3.921, p = 0.002], Charlson Comorbidity Index (HR 1.181, p = 0.004), Coagulase-negative staphylococci (HR 4.233, p = 0.001), new-onset central nervous system complications (HR 3.689, p < 0.001), and new-onset heart failure (HR 4.331, p = 0.001) were significant risk factors for overall mortality. CONCLUSIONS: Valve culture positivity is a significant risk factor for long-term overall mortality in IE patients who underwent valve surgery. The importance of valve culture positivity needs to be re-evaluated, as the valve culture positivity rate increases with increasing early surgical intervention.

Clinical characteristics of nontuberculous mycobacterial disease in people living with HIV/AIDS in South Korea: A multi-center, retrospective study.

With the introduction of combination antiretroviral therapy (cART), the prevalence of human immunodeficiency virus (HIV)-associated nontuberculous mycobacteria (NTM) disease has declined. However, NTM diseases still occur in people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA). We analysed the clinical and microbiological features of NTM diseases in PLWHA in South Korea. PLWHA who were diagnosed with NTM diseases between January 2000 and March 2021 were retrospectively enrolled from five different hospitals in South Korea. Data on baseline demographics, HIV status, CD4+ T cell counts, viral load, past and current cART regimens, isolated NTM species, results of antimicrobial susceptibility tests, treatment regimens, and outcomes were collected by reviewing medical records. A total of 34 cases of NTM in PLWHA were included. Pulmonary and extrapulmonary NTM diseases accounted for 58.8% (n = 20) and 41.2% (n = 14), respectively. The lymph node was the most common site of extrapulmonary NTM disease (64.3%). The age at the time of NTM disease diagnosis was younger in the extrapulmonary NTM group than in the pulmonary NTM group (37.0 vs. 49.0 years). Mean CD4+ T cell counts at the time of NTM disease diagnosis was 186.6 cells/µL (range: 1-1394). Nine patients (26.5%) had fully suppressed viral loads at the time of NTM disease diagnosis. Mycobacterium avium complex (MAC) was the most common species found, followed by M. intracellulare and M. kansasii. MAC isolates were all susceptible to clarithromycin, but the rates of non-susceptibility to moxifloxacin, linezolid, ethambutol, and rifampin were 75%, 37.5%, 12.5%, and 12.5%, respectively. The average duration of treatment was 17 months and the mortality rate was 8.8%. NTM diseases may occur in PLWHA, even with completely suppressed viral loads. The identified clinical features of NTM diseases are essential for its clinical management in South Korea.

Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms.

BACKGROUND: Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. METHODS: A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. RESULTS: Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. CONCLUSION: FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.

Estimation of SARS-CoV-2 Neutralizing Activity and Protective Immunity in Different Vaccine Types Using Three Surrogate Virus Neutralization Test Assays and Two Semiquantitative Binding Assays Targeting the Receptor-Binding Domain.

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.

Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea.

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.

The Prediction and Prognosis of Fungal Infection in Lung Transplant Recipients-A Retrospective Cohort Study in South Korea.

(1) Background: Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods: The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results: Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions: Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.