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We do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts: cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.

Poor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown.We conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis.A total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73-0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14-6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13-2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23-5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization.Several clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.

BackgroundImmune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated.MethodsA nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant–confirmed patients.ResultsA total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O2 support (18.4% vs. 27.1%, P < 0.001) and progressed to severe disease (4.0% vs. 8.0%, P < 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O2 support (HR 0.677, 95% CI 0.561–0.816) and progression to severe disease (HR 0.489, 95% CI 0.337–0.709). Among the 939 delta-confirmed patients, O2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O2 support (HR 0.963, 95% CI 0.697–1.329) or progression to severe disease (HR 0.665, 95% CI 0.349–1.268) in delta-confirmed group.ConclusionsRegdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.

Backgrounds: This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without HSCT. Methods: We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease. Results: Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p

IntroductionThe effect of tixagevimab/cilgavimab (Evusheld™; AstraZeneca, UK) should be evaluated in the context of concurrent outbreak situations.MethodsFor serologic investigation of tixagevimab/cilgavimab during the BA.5 outbreak period, sera of immunocompromised (IC) hosts sampled before and one month after tixagevimab/cilgavimab administration and those of healthcare workers (HCWs) sampled one month after a 3rd shot of COVID-19 vaccines, five months after BA.1/BA.2 breakthrough infection (BI), and one month after BA.5 BI were investigated. Semi-quantitative anti-spike protein antibody (Sab) test and plaque reduction neutralizing test (PRNT) against BA.5 were performed.ResultsA total of 19 IC hosts (five received tixagevimab/cilgavimab 300 mg and 14 received 600 mg) and 41 HCWs (21 experienced BA.1/BA.2 BI and 20 experienced BA.5 BI) were evaluated. Baseline characteristics did not differ significantly between IC hosts and HCWs except for age and hypertension. Sab significantly increased after tixagevimab/cilgavimab administration (median 130.2 BAU/mL before tixagevimab/cilgavimab, 5,665.8 BAU/mL after 300 mg, and 10,217 BAU/mL after 600 mg; both P < 0.001). Sab of one month after the 3rd shot (12,144.2 BAU/mL) or five months after BA.1/BA.2 BI (10,455.8 BAU/mL) were comparable with that of tixagevimab/cilgavimab 600 mg, while Sab of one month after BA.5 BI were significantly higher (22,216.0 BAU/mL; P < 0.001). BA.5 PRNT ND50 significantly increased after tixagevimab/cilgavimab administration (median ND50 29.6 before tixagevimab/cilgavimab, 170.8 after 300 mg, and 298.5 after 600 mg; both P < 0.001). The ND50 after tixagevimab/cilgavimab 600 mg was comparable to those of five months after BA.1 BI (ND50 200.9) while ND50 of one month after the 3rd shot was significantly lower (ND50 107.6; P = 0.019). The ND50 of one month after BA.5 BI (ND50 1,272.5) was highest among tested groups, but statistical difference was not noticed with tixagevimab/cilgavimab 600 mg.ConclusionTixagevimab/cilgavimab provided a comparable neutralizing activity against the BA.5 with a healthy adult population who were vaccinated with a 3rd shot and experienced BA.1/BA.2 BI.

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 (ND

Background Acinetobacter baumannii is one of the leading etiologic agents of serious hospital-acquired infections. A. baumannii is characterized by a high rate of carbapenem resistance, which often leads to treatment failure and poor outcome. Combination regimens of antibiotics are often used, but their clinical benefit and optimal target are yet unclear. Methods We selected carbapenem-resistant A. baumannii (CRA) isolates from the patients who received antimicrobial treatment for bloodstream infection (2012–2018) or pneumonia (2019–2020) and survived for ≥5 days. In vitro synergy was tested using checkerboard method and time-kill assay for colistin (COL) and tigecycline (TGC) with the following antibiotics: meropenem (MRO), ampicillin/sulbactam (A/S), minocycline (MIN), ciprofloxacin (CIP), and with each other. Clinical information was collected to compare the patient outcome between those who were treated with combination regimens with in vitro synergy and those who were not. Results A total of 72 isolates were selected. When combined with colistin, MRO showed the highest rate of synergy (20.8%), followed by A/S (16.7%), and MIN (13.9%). No antibiotics showed synergy with TGC in >10% of the tested isolates. Most isolates with positive checkerboard test also tested positive with time-kill assay for COL (97.6%), but not for TGC (20.0%). Among 57 patients with monobacterial infection caused by the tested CRA isolates, nine (15.8%) received combination regimens with in vitro synergy. All patients received colistin, and carbapenem was the companion antibiotic in all patients in the synergistic combination group. There was no significant difference in all-cause 30-day mortality (55.6% vs 33.3%, p=0.266), treatment response, and microbiologic response. Multivariable analysis also demonstrated no significant difference in mortality by synergistic combination regimen (adjusted odds ratio, 4.59; 95% confidence interval, 0.73–33.88). Conclusion Checkerboard method showed an excellent concordance with time-kill assay for COL-based combinations, but not with TGC-based regimens. However, combination regimens with a proven in vitro synergy were not associated with better outcomes. Disclosures All Authors: No reported disclosures.

BackgroundThe impact of nirmatrelvir/ritonavir treatment on shedding of viable virus in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear.MethodsA prospective cohort study evaluating mildly ill COVID-19 patients was conducted. Virologic responses were compared between nirmatrelvir/ritonavir-treatment and supportive care groups. Risk factors and relevant clinical factors for shedding of viable virus were investigated.ResultsA total of 80 COVID-19 patients were enrolled and 222 sputum specimens were collected. Ten patients were dropped during follow-up, and 33 patients in the nirmatrelvir/ritonavir and 37 in the supportive care groups were compared. The median age was 67 years, and 67% were male. Clinical characteristics were similar between groups. Viral loads decreased significantly faster in the nirmatrelvir/ritonavir group compared with the supportive care group (P < 0.001), and the slope was significantly steeper (–2.99 ± 1.54 vs. –1.44 ± 1.52; P < 0.001). The duration of viable virus shedding was not statistically different between groups. In the multivariable analyses evaluating all collected specimens, male gender (OR 2.51, 95% CI 1.25–5.03, P = 0.010), symptom score (OR 1.41, 95% CI 1.07–1.87, P = 0.015), days from symptom onset (OR 0.72, 95% CI 0.59–0.88, P = 0.002), complete vaccination (OR 0.09, 95% CI 0.01–0.87, P = 0.038), and BA.2 subtype (OR 0.49, 95% CI 0.26–0.91, P = 0.025) were independently associated with viable viral shedding, while nirmatrelvir/ritonavir treatment was not.ConclusionNirmatrelvir/ritonavir treatment effectively reduced viral loads of SARS-CoV-2 Omicron variants but did not decrease the duration of viable virus shedding.

IntroductionDespite 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.MethodsWe 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.ResultsWe 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).ConclusionDecreased 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.

Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p < 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55–3.19; p < 0.001) and for bacteremia (OR 5.18, 95% CI 3.13–8.56; p < 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67–6.54; p < 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker.

Purpose To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. Methods We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration–time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. Results A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539–0.886; AUC for Ctrough, 0.760; 95% CI 0.627–0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 μg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60–86.62; p = 0.010). Conclusion Mean Ctrough ≥ 13.94 μg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Background/Aims: Human adenovirus type 55 (HAdV-55), an emerging epidemic strain, has caused several large outbreaks in the Korean military since 2014, and HAdV-associated acute respiratory illness (HAdV-ARI) has been continuously re ported thereafter. Methods: To evaluate the epidemiologic characteristics of HAdV-ARI in the Ko rean military, we analyzed respiratory virus polymerase chain reaction (RV-PCR) results, pneumonia surveillance results, and severe HAdV cases from all 14 Ko rean military hospitals from January 2013 to May 2018 and compared these data with nationwide RV surveillance data for the civilian population. Results: A total of 14,630 RV-PCRs was performed at military hospitals. HAdV (45.4%) was the most frequently detected RV, followed by human rhinovirus (12.3%) and influenza virus (6.3%). The percentage of the military positive for HAdV was significantly greater than the percentage of civilians positive for HAdV through out the study period, with a large outbreak occurring during the winter to spring of 2014 to 2015. The outbreak continued until the end of the study, and non-sea sonal detections increased over time. The reported number of pneumonia pa tients also increased during the outbreak. Case fatality rate was 0.075% overall but 15.6% in patients with respiratory failure. The proportion of severe patients did not change significantly during the study period. Conclusions: A large HAdV outbreak is currently ongoing in the Korean mili tary, with a trend away from seasonality, and HAdV-55 is likely the predominant strain. Persistent efforts to control the outbreak, HAdV type-specific surveillance, and vaccine development are required.

Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27–12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications. Electronic supplementary material The online version of this article (10.1007/s10096-020-04074-5) contains supplementary material, which is available to authorized users.

BACKGROUND: Human adenovirus (HAdV) can cause severe community-acquired pneumonia, but there are few studies on the associated cytokine patterns. The purpose of this study was to analyze the relationship between inflammatory cytokine and severity of adenovirus pneumonia. METHODS: This was a prospective observational study. We evaluated pneumonia patients admitted to the Armed Forces Capital Hospital in Korea. On admission, blood samples were acquired from patients who showed signs of pneumonia. HAdV infection was diagnosed using Real-Q RV detection Kit, and types of HAdV were confirmed by nucleotide blast analysis. We used enzyme-linked immunosorbent assays (ELISAs) to quantify the serum levels of cytokines [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, γ-interferon (IFN-γ), and IL-10]. We evaluated clinical characteristics and cytokine patterns. RESULTS: Of 74 pneumonia patients, respiratory specimens from 43 tested positive for HAdV-55, and the other 31 tested negatives. The length of hospital stay was significantly longer in the HAdV group. The serum concentrations of IL-6, IL-8, IL-10, and IFN-γ were all significantly higher in the HAdV group. Of the 43 HAdV pneumonia patients, 6 evidenced PaO(2)/FiO(2) (PF) ratio

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.

Background We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available. Methods Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005–2018 was analyzed. Results Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531–0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981–1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend. Conclusions During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems.

Background: Treatment of device-related infections by drug-resistant Staphylococcus aureus can be challenging, and combination therapy has been proposed as a potential solution. We compared the effectiveness of levofloxacin–rifampin and ciprofloxacin–rifampin combinations in killing methicillin-resistant S. aureus (MRSA) using a time–kill assay. Methods: We randomly selected 15 vancomycin-susceptible S. aureus (VSSA) strains, 3 vancomycin-intermediate S. aureus (VISA) strains, and 12 heterogeneous VISA (hVISA) strains from the Asian Bacterial Bank. Time–kill experiments were performed in duplicate for each isolate. Viable bacterial counts were determined at 0 h, 4 h, 8 h, and 24 h for the ciprofloxacin– and levofloxacin–rifampin combinations at 1× MIC and 0.5× MIC. We compared synergistic and antagonistic interactions between the two combinations. Results: The viable bacterial count significantly decreased after 24 h of exposure to ciprofloxacin–rifampin and levofloxacin–rifampin combinations, with synergy observed more frequently in isolates exposed to ciprofloxacin–rifampin (43.3%) than levofloxacin–rifampin (20.0%) (p = 0.0082). The synergistic interactions of both combinations were more frequently observed in resistant strains with high MICs of ciprofloxacin (≥16 mg/L) and levofloxacin (≥8 mg/L). Levofloxacin tended to exhibit more frequent antagonistic interactions with rifampin than ciprofloxacin, although there was no statistical difference in antagonism between the two combinations. Conclusions: Our study demonstrated that ciprofloxacin exhibits superior synergistic activity against MRSA strains, including VISA/hVISA, when combined with rifampin compared with levofloxacin. High MICs of fluoroquinolones were found to predict synergism. Our results suggest that ciprofloxacin may be a more effective choice than levofloxacin for combination therapy with rifampin in the treatment of MRSA infections.

Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia.We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups.Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494).We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin.

ObjectiveTo evaluate clinical effectiveness of regdanvimab, a monoclonal antibody agent for treating coronavirus 2019 (COVID-19).MethodsA retrospective cohort study was conducted at two general hospitals during the study period of December 2020 to May 2021. Mild COVID-19 patients with risk factors for disease progression admitted to the hospitals within seven days of symptom onset were enrolled and followed until discharge or referral. Multivariate analyses for disease progression were conducted in the total and propensity score (PS)-matched cohorts.ResultsA total of 778 mild COVID-19 patients were included and classified as the regdanvimab (n = 234) and supportive care (n = 544) groups. Significantly fewer patients required O2 supplementation via nasal prong in the regdanvimab group (8.1%) than in the supportive care group (18.4%, P < 0.001). The decreased risk for O2 support by regdanvimab treatment was noticed in the multivariate analysis of the total cohort (HR 0.570, 95% CI 0.343–0.946, P = 0.030), but it was not statistically significant in the PS-matched cohort (P = 0.057). Progression to severe disease was also significantly lower in the regdanvimab group (2.1%) than in the supportive care group (9.6%, P < 0.001). The significantly reduced risk for progression to severe disease by regdanvimab treatment was observed in the analysis of both the total cohort (HR 0.262, 95% CI 0.103–0.667, P = 0.005) and PS-matched cohort (HR 0.176, 95% CI 0.060–0.516, P = 0.002). Potential risk factors for progression were investigated in the supportive care group and SpO2 < 97% and CRP elevation >1.5 mg/dL were common risk factors for O2 support and progression to severe disease. Among the patients with any of these factors, regdanvimab treatment was associated with decreased risk for progression to severe disease with slightly lower HR (HR 0.202, 95% CI 0.062–0.657, P = 0.008) than that of the total cohort.ConclusionRegdanvimab treatment was associated with a decreased risk of progression to severe disease.

Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated.A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery.A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.

Snoring is a sleep disorder that may have adverse effects on an individual's health and social activities. Polysomnography is the most common way to diagnose snoring but involves considerable time and cost. Many recent studies have attempted to classify snoring and non-snoring. However, since the length, frequency, and period of snoring episodes (SE) differ according to the individual being measured, it is very difficult to develop a general reference point to classify snoring. Therefore, in order to classify different snoring patterns and noise for different individuals, a learning-based snoring classification algorithm is essential. To this end, this study proposes a classification method based on a recurrent neural network (RNN) that can classify SEs and non-snoring episodes (NSEs) by learning the features of an individual's SEs and NSEs, measured in daily life based on the subjects’ sleep recordings using smartphone. The method proposed in this study can be largely divided into segmentation, feature extraction, and classification. The performance of this study was evaluated through statistical parameters. Despite the fact that the proposed RNN-based classifiers were trained using a relative small dataset, they exhibited an extremely high accuracy of 98.9%.

We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups.We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey.We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p 0.001). The neutralizing antibody titer of the heterologous group (geometric mean NDHeterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.

Background The difference in clinical outcomes between Klebsiella aerogenes (formerly Enterobacter aerogenes) bacteremia (KAB) and Enterobacter cloacae complex bacteremia (ECB) is controversial. Methods We compared the clinical outcomes of patients with KAB and ECB and examined the risk factors associated with mortality. We conducted a retrospective case-control study of hospitalized patients with monobacterial KAB and ECB between January 2011 and June 2020. The primary outcome measure was 30-day all-cause mortality. Multiple logistic regression and propensity-score (PS) matching were used to identify independent risk factors for mortality. The models included demographic characteristics, comorbidities, recent healthcare contact, patient status at the onset of bacteremia, and severity of infection as covariates. Results A total of 282 patients with KAB or ECB were included, among whom 194 patients were selected after PS matching. The 30-day all-cause mortality rate was higher in the ECB group than in the KAB group (24.1% vs 10.6%, P = .003). In a multivariable model, ECB was an independent risk factor for 30-day mortality in both overall and PS-matched cohorts (adjusted odds ratio, 3.528; 95% confidence interval, 1.614–7.714; P = .002). Stay in the intensive care unit at the onset of bacteremia and higher Pitt bacteremia score were found to be independent risk factors for 30-day mortality. Conclusions In our study, mortality was significantly higher in patients with ECB than in those with KAB. Further studies are warranted to clarify the virulence mechanisms of E cloacae complex.

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20–71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0–18.0) compared to those in the ChAd group (median 23.0, IQR 8.0–43.0,P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0–9.0,P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL,P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL,P=0.002) and BNT (1.656 ± 1.925 IU/mL,P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.

Back ground. Asymptomatic/mildly symptomatic coronavirus disease 2019 (COVID-19) patients produce a considerable amount of virus and transmit severe acute respiratory syndrome virus 2 (SARS-CoV-2) through close contact. Preventing in-hospital transmission of SARS-CoV-2 is challenging, since symptom-based screening protocols may miss asymptomatic/mildly symptomatic patients. In particular, dental health workers (HCWs) are at high risk of exposure, as face-to-face contact and exposure to oral secretions is unavoidable. We report exposure of HCWs during dental procedures on a mild symptomatic COVID-19 patient. Methods. A 32-year old male visited a dental clinic at a tertiary care hospital. He experienced mild cough, which started three days before the dental visit, but did not report his symptom during the entrance screening. He underwent several dental procedures and imaging for orthognathic surgery without wearing a mask. Seven HCWs were closely exposed to the patient during dental procedures that could have generated droplets and aerosols. One HCW had close contact with the patient during radiologic exams, and seven HCWs had casual contact. All HCWs wore particulate filtering respirators with 94% filter capacity and gloves, but none wore eye protection or gowns. The next day, the patient experienced dysgeusia and was diagnosed with COVID-19 with high viral load. Results. All HCWs who had close contact with the patient were quarantined for 14 days, and polymerase chain reaction and antibody tests for SARS-CoV-2 were negative. Conclusion. This exposure event suggests the protective effect of particulate filtering respirators in dental clinics. The appropriate personal protective equipment for routine patient care during COVID-19 pandemic should be established. The appropriate personal protective equipment for routine patient care during COVID-19 pandemic should be established.

Background Reactivation of human cytomegalovirus (CMV) occurs in non-immunocompromised patients with or without specific organ involvement, but it is still unknown whether it has a clinical implication on long-term prognosis or not. Methods A retrospective cohort study evaluating non-immunocompromised adult patients with CMV reactivation was conducted during the period between January 2010 and February 2018. Patients were divided into ganciclovir-treated and non-treated groups. Patients who died within 30 days from CMV reactivation were excluded as they died from complex causes of conditions. Survivors were followed for 30-months to evaluate long-term prognosis. Results A total of 136 patients with CMV reactivation was included, consisting of 66 ganciclovir-treated (48.5%) and 70 non-treated (51.5%) patients. Overall, patients were old-aged (median 70 years old) and most were treated with pneumonia of any cause (91.2%). More patients in ganciclovir-treated group were treated at intensive care unit (43.9% vs 24.3%, respectively) and had higher viral load over 5000 copies/ml (48.5% vs 22.9%) than non-treated group (all P Conclusion In a retrospective cohort study evaluating non-immunocompromised patients with CMV reactivation, ganciclovir treatment was not associated with long-term prognosis. Antiviral treatment in this condition would not be necessary unless organ involvement is suspected.

Background Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. Methods A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. Results A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). Conclusion The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19., Graphical Abstract

Since mid-April 2020, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 that mimics Kawasaki disease (KD) have been reported in Europe and North America. However, no cases have been reported in Korea. We describe an 11-year old boy with fever, abdominal pain, and diarrhea who developed hypotension requiring inotropes in intensive care unit. His blood test revealed elevated inflammatory markers, thrombocytopenia, hypoalbuminemia, and coagulopathy. Afterward, he developed signs of KD such as conjunctival injection, strawberry tongue, cracked lip, and coronary artery dilatation, and parenchymal consolidation without respiratory symptoms. Microbiological tests were all negative including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction. However, serum immunoglobulin G against SARS-CoV-2 was positive in repeated tests using enzyme-linked immunosorbent assay and fluorescent immunoassay. He was recovered well after intravenous immunoglobulin administration and discharged without complication on hospital day 13. We report the first Korean child who met all the criteria of MIS-C with features of incomplete KD or KD shock syndrome., Graphical Abstract

The safety of healthcare workers (HCWs) against severe acute respiratory syndrome virus 2 (SARS-CoV-2) transmission is an important aspect of managing the coronavirus disease 2019 (COVID-19) pandemic. In the South Korea, highly stringent infection prevention and control (IPC) guidelines are implemented, and reports of healthcare-associated SARS-CoV-2 transmission among HCWs are limited. However, subclinical infections may have been missed by the current symptom-based screening strategy. To evaluate the risk of undetected SARS-CoV-2 transmissions from COVID-19 patients to HCWs, we conducted a multicenter seroprevalence study after the first surge of the COVID-19 outbreak. A total of 432 HCWs were evaluated, comprising 309 HCWs designated to laboratory-confirmed COVID-19 patient care and 123 non-designated HCWs. Designated HCWs wore personal protective equipment including an N95 respirator, eye protection, hooded overalls, shoe covers, and inner and outer gloves. Use of a powered air-purifying respirator was recommended for aerosol-generating procedures or long-duration care activities. A high-sensitivity (99.1%) fluorescence immunoassay immunoglobulin G (IgG) kit was used as the initial screening test, and two enzyme-linked immunosorbent assay kits for total and IgG antibodies were used to confirm the test results. A microneutralization test was additionally performed to evaluate the neutralizing activity of positive specimens. Among the evaluated HCWs, none of the non-designated HCWs had a positive result, while one of the HCWs designated for COVID-19 patient care (1/309, 0.3%) was seropositive for SARS-CoV-2 with confirmed neutralizing activity (1:40). This finding suggests that subclinical seroconversion may occur among HCWs caring for COVID-19 patients, although the risk is low under strict IPC guidance.

Poly(l-lactic acid) (PLLA) based piezoelectric polymers are gradually becoming the substitute for the conventional piezoelectric ceramic and polymeric materials due to their low cost and biodegradable, non-toxic, piezoelectric and non-pyroelectric nature. To improve the piezoelectric properties of melt-spun poly(l-lactic acid) (PLLA)/BaTiO3, we optimized the post-processing conditions to increase the proportion of the β crystalline phase. The α → β phase transition behaviour was determined by two-dimensional wide-angle x-ray diffraction and differential scanning calorimetry. The piezoelectric properties of PLLA/BaTiO3 fibres were characterised in their yarn and textile form through a tapping method. From these results, we confirmed that the crystalline phase transition of PLLA/BaTiO3 fibres was significantly enhanced under the optimised post-processing conditions at a draw ratio of 3 and temperature of 120 °C during the melt-spinning process. The results indicated that PLLA/BaTiO3 fibres could be a one of the material for organic-based piezoelectric sensors for application in textile-based wearable piezoelectric devices.