Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Cost-effectiveness analysis of cell-based versus egg-based quadrivalent influenza vaccines in the pediatric population in Taiwan.

Cell-based influenza vaccines avoid egg-adaptive mutations, potentially improving vaccine effectiveness. We assessed the one-season cost-effectiveness of cell-based quadrivalent influenza vaccine (QIVc) against that of egg-derived quadrivalent influenza vaccines (QIVe) in children (6 months to 17 years of age) from payer and societal perspectives in Taiwan using an age-stratified static model. Base case and high egg adaptation scenarios were assessed. Deterministic and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratio (ICER) threshold in Taiwan was assumed to be USD 99 177/quality-adjusted life year (QALY). Compared to QIVe, QIVc would prevent 15 665 influenza cases, 2244 complicated cases, and 259 hospitalizations per year. The base case ICER was USD 68 298/QALY and USD 40 085/QALY from the payer and societal perspective, respectively. In the high egg adaptation scenario, the ICER was USD 45 782/QALY from the payer's perspective and USD 17 489/QALY from the societal perspective. Deterministic sensitivity analyses indicated that infection incidence rate, vaccination coverage, and prevalence of the A/H3N2 strain were the main drivers of ICER. In conclusion, switching the immunization strategy from QIVe to QIVc is predicted to reduce the influenza-associated disease burden and be cost-effective for the pediatric population in Taiwan. The potential benefits of QIVc would be even higher during influenza seasons with high levels of egg adaptation.

Molecular and Phenotypic Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates in Taiwan.

Purpose: Staphylococcus epidermidis, a commensal, has emerged as an important opportunistic pathogen, particularly methicillin-resistant S. epidermidis (MRSE). The mechanism behind this transformation remains unclear. This study aimed to investigate the molecular and phenotypic characteristics of MRSE isolated from healthy conjunctiva and ocular infections. Methods: We collected MRSE isolates from two groups: healthy conjunctiva from patients undergoing cataract surgeries and ocular infections at our hospital. Genotypic analysis included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec), and biofilm-related genes (icaA, aap, and bhp). Additionally, phenotypic data on biofilm production and antibiotic susceptibility were recorded. Results: A total of 86 isolates, including 42 from healthy conjunctiva and 44 from ocular infections, were analyzed. MLST identified 21 sequence types (STs), with ST59 being the most frequent (n = 33, 39.5%), followed by ST130 (n = 10, 11.6%), ST57 (n = 6, 7.0%), and ST2 (n = 6, 7.0%). All isolates were categorized in 23 PFGE types, and SCCmec IV was the most prevalent SCCmec type (n = 52, 60.5%). The two sources of isolates exhibited overlapping molecular types and phenotypic traits, although the ocular infection isolates exhibited significantly higher multidrug resistance compared to healthy conjunctiva isolates (P = 0.032). When contrasting ST59 with non-ST59, ST59 displayed a significantly higher presence of aap (100%) and bhp (69.7%) while lacking icaA (0%). ST59 also showed lower susceptibility to fluoroquinolones compared to non-ST59 (42.4%-54.5% vs. 75.5%-83.0%; P < 0.01). Conclusions: MRSE isolates from healthy conjunctiva and ocular infections demonstrated a degree of resemblance. Specific strains, notably ST59, exhibited distinctive characterizations.

Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children.

BACKGROUND: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. METHODS: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. RESULTS: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/µL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy. CONCLUSIONS: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.

Molecular characteristics and clinical features of Staphylococcus epidermidis healthcare-associated late-onset bacteremia among infants hospitalized in neonatal intensive care units.

BACKGROUND: Though Staphylococcus epidermidis was the most common pathogen of late-onset sepsis (LOS) in neonatal intensive care units (NICUs), there haves been scanty reports on molecular epidemiology of S. epidermidis isolates from infants stayed in NICU and on correlation of molecular characteristics with clinical features in these infants. METHODS: We collected and characterized S. epidermidis bloodstream isolates from infants hospitalized in NICU of a medical center in Taiwan between 2018 and 2020. Medical records of these infants were retrospectively reviewed. RESULTS: A total of 107 isolates identified from 78 episodes of bacteremia in 75 infants were included for analysis. Of the 78 isolates (episodes), 24 pulsotypes, 11 sequence types (STs), and 5 types of staphylococcal chromosomal cassette (type I-V) were identified. ST59 and its single locus variant ST1124 (37.2%) comprised the most common strain, followed by ST35 (14.1%), ST2 (11.5%), and ST89 (10.3%). All but 5 isolates (73/78, 93.6%) belonged to clonal complex (CC) 2. Comparing infants infected with genetically different strains, the patients with underlying immune disease were significantly associated with ST2 infection (P = 0.021), while no statistically significant differences were found in terms of clinical and laboratory characteristics. Only 3.8% of the isolates were susceptible to oxacillin. CONCLUSIONS: More than 90% of S. epidermidis bloodstream isolates from infants in NICU in Taiwan were resistant to oxacillin. Though diverse, more than 90% of the isolates (episodes) belonged to CC2. No statistically significant differences were found in terms of clinical characteristics among the infants infected with genetically different strains.

Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial.

Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.

Methicillin-Resistant Staphylococcus aureus Ocular Infection in Taiwan: Potential Role of Panton-Valentine Leukocidin Gene.

Purpose: The relationship between Panton-Valentine leucocidin (PVL), a major virulence factor of Staphylococcus aureus, and disease severity and clinical outcomes remains unclear. We investigated the molecular characteristics and role of the PVL gene in methicillin-resistant S. aureus (MRSA) ocular infection in Taiwan. Methods: Patients with culture-proven S. aureus ocular infection in Chang Gung Memorial Hospital from 2010 to 2017 were included. The presence of the PVL gene was detected for all S. aureus isolates. MRSA isolates were characterized through pulsed-field gel electrophoresis (PFGE), staphylococcal multilocus sequence type, and staphylococcal cassette chromosome mec (SCCmec) typing. Drug susceptibility was examined using disk diffusion method and E-test. Patients' demographics, diagnoses, and outcomes were collected. Results: There were 112 methicillin-sensitive S. aureus and 103 MRSA isolates. Among 50 PVL(+) S. aureus isolates, 43 were MRSA. CC59/PFGE type D/SCCmec IV, VT (38 of 43 isolates, 88%), and CC59/PFGE type C/SCCmec IV (27 of 60 isolates, 45%) were the predominant clones in the PVL(+) and PVL(-) MRSA isolates, respectively. When we compared the two CC59 strains, the patients with PVL(+)/CC59 MSRA infection were significantly younger than those with PVL(-)/CC59 MSRA (39.3 vs. 61.7 years; P = 0.001). PVL(+)/CC59 MSRA caused significantly more eyelid disorders (36.8% vs. 3.7%; P = 0.002) but less keratitis (23.7% vs. 51.9%; P = 0.034). The antibiograms of the two strains were similar. Conclusions: PVL(+) MRSA is significantly associated with eyelid infection, especially in young patients. Translational Relevance: PVL gene plays a role in clinical features of MRSA ocular infections.

Clinical manifestations and risk factors of campylobacter gastroenteritis in children in Taiwan.

BACKGROUND: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. METHODS: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. RESULTS: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis. CONCLUSIONS: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake.

Targeted Literature Review of the Burden of Respiratory Syncytial Infection among High-Risk and Elderly Patients in Asia Pacific Region.

INTRODUCTION: The burden of respiratory syncytial virus (RSV), which causes acute respiratory illness, is well recognized among the pediatric population but also imposes a significant risk to the elderly (age ≥ 60) and those with underlying comorbidities. The study aimed to review the most recent data on epidemiology and burden (clinical and economic) of RSV in the elderly/high-risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted review was conducted of English, Japanese, Korean, and Chinese language articles published from 1 January 2010 to 7 October 2020 relevant for the purpose. RESULTS: A total of 881 studies were identified, and 41 were included. The median proportion of elderly patients with RSV in all adult patients with acute respiratory infection (ARI) or community acquired pneumonia was 79.78% (71.43-88.12%) in Japan, 48.00% (3.64-80.00%) in China, 41.67% (33.33-50.00%) in Taiwan, 38.61% in Australia, and 28.57% (22.76-33.33%) in South Korea. RSV was associated with a high clinical burden on those patients with comorbidities such as asthma and chronic obstructive pulmonary disease. In China, inpatients with ARI showed a significantly higher rate of RSV-related hospitalization than outpatients (13.22% versus 4.08%, p < 0.01). The median length of hospital stay among elderly patients with RSV was longest in Japan (30 days) and shortest in China (7 days). Mortality data varied by region with some studies reporting rates as high as 12.00% (9/75) in hospitalized elderly patients. Finally, data on the economic burden was only available for South Korea, with the median cost of a medical admission for an elderly patient with RSV being US dollar (USD) 2933. CONCLUSION: RSV infection is a major source of disease burden among elderly patients, especially in regions with aging populations. It also complicates the management of those with underlying diseases. Appropriate prevention strategies are required to reduce the burden among the adult, especially the elderly, population. Data gaps regarding economic burden of RSV infection in the Asia Pacific region indicates the need for further research to increase our understanding on the burden of this disease in this region.

The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain. METHODS: The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively. RESULTS: Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively. CONCLUSION: The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.

Longitudinal investigation of pathogenic bacterial colonization in early childhood: Emphasis on the determinants of Moraxella catarrhalis colonization.

BACKGROUND: Moraxella catarrhalis is a common, potential pathogen colonizing the respiratory tract in children. However, there is little information regarding the determinants of M. catarrhalis colonization and disease development. METHODS: A population-based cohort study was conducted to collect nasopharyngeal swabs from children aged 1, 2, 4, 6, 12, 18, 24, 36, and 60 months for the detection of four common respiratory tract pathogens, including Staphylococcus aureus, M. catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae. Questionnaires on breastfeeding status were administered during each visit. RESULTS: A total of 921 children were enrolled between 2012 and 2018. S.aureus was the most common pathogen, although the rates declined during the initial 18 months of life; in contrast, the other three pathogens increased during the first 5 years of life. M. catarrhalis was the second most common colonizing pathogen in all age groups, with prevalence ranging from 0.8% (7/842) at one month to 20.4% (33/162) at 60 months of age. Breastfed children (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.35-0.92; P = 0.02) had a lower potential for M. catarrhalis carriage; however, infants with a longer duration of exclusive breastfeeding (OR: 1.12; 95% CI: 1.01-1.25; P = 0.04), especially >12 months of age, had a higher rate of M. catarrhalis carriage. CONCLUSION: Breastfeeding should be promoted because it may be correlated with a lower risk of M. catarrhalis carriage. However, an extended period of exclusive breastfeeding may be positively associated with M. catarrhalis colonization.

Staphylococcus aureus Keratitis in Taiwan: Genotyping, Antibiotic Susceptibility, and Clinical Features.

Staphylococcus aureus is an important pathogen for keratitis, a vision-threatening disease. We aimed to investigate the genotyping, antibiotic susceptibility, and clinical features of S. aureus keratitis, and to explore the possible role of Panton-Valentine leucocidin (PVL), a major virulence factor of S. aureus. We recruited 49 patients with culture-proven S. aureus keratitis between 2013 and 2017 at Chang Gung Memorial Hospital, Taiwan. PVL gene, multilocus sequence type (MLST), staphylococcal cassette chromosome mec (SCCmec), and pulsed-field gel electrophoresis (PFGE) were performed. Antibiotic susceptibility was verified using disk diffusion/E test. There were 49 patients with S. aureus keratitis; 17 (34.7%) were caused by methicillin-resistant S. aureus (MRSA) and 9 (18.4%) isolates had PVL genes. The predominant genotyping of MRSA isolates was CC59/PFGE type D/SCCmec VT/PVL (+). All methicillin-sensitive S. aureus (MSSA) and approximately 60% MRSA were susceptible to fluoroquinolones. No significant differences in clinical features, treatments, and visual outcomes were observed between MRSA/MSSA or PVL(+)/PVL(-) groups. In Taiwan, approximately one third of S. aureus keratitis was caused by MRSA, mainly community-associated MRSA. Although MRSA isolates were more resistant than MSSA, clinical characteristics were similar between two groups. Fluoroquinolones could be good empiric antibiotics for S. aureus keratitis.

A randomized controlled trial of heterologous ChAdOx1 nCoV-19 and recombinant subunit vaccine MVC-COV1901 against COVID-19.

Heterologous prime-boost COVID-19 vaccine strategy may facilitate mass COVID-19 immunization. We reported early immunogenicity and safety outcomes of heterologous immunization with a viral vector vaccine (ChAdOx1) and a spike-2P subunit vaccine (MVC-COV1901) in a participant-blinded, randomized, non-inferiority trial (NCT05054621). A total of 100 healthy adults aged 20-70 years having the first dose of ChAdOx1 were 1:1 randomly assigned to receive a booster dose either with ChAdOx1 (n = 50) or MVC-COV1901 (n = 50) at an interval of 4-6 or 8-10 weeks. At day 28 post-boosting, the neutralizing antibody geometric mean titer against wild-type SARS-CoV-2 in MVC-COV1901 recipients (236 IU/mL) was superior to that in ChAdOx1 recipients (115 IU/mL), with a GMT ratio of 2.1 (95% CI, 1.4 to 2.9). Superiority in the neutralizing antibody titer against Delta variant was also found for heterologous MVC-COV1901 immunization with a GMT ratio of 2.6 (95% CI, 1.8 to 3.8). Both spike-specific antibody-secreting B and T cell responses were substantially enhanced by the heterologous schedule. Heterologous boosting was particularly prominent at a short prime-boost interval. No serious adverse events occurred across all groups. The findings support the use of heterologous prime-boost with ChAdOx1 and protein-based subunit vaccines.

Impacts of Catch-Up Immunization program with the 13-Valent pneumococcal Conjugate vaccine in Taiwan: Focus on age-stratified differences and high-risk population (2001-2015).

BACKGROUND: Taiwan commenced a national catch-up immunization program with a 13-valent pneumococcal conjugate vaccine (PCV13) in 2013 for children aged 2-5 years old and in 2014 for children aged 1-5 years old. However, real-world nationwide evidence of both the direct protection and indirect protection of all-cause pneumonia and pneumococcal pneumonia has been scarce, especially among high-risk populations, defined as patients with chronic diseases or immunosuppression. The aim of this study was to examine the impact of the national PCV13 catch-up program on all-cause pneumonia and pneumococcal pneumonia among overall and high-risk populations using interrupted time series analysis. METHODS: Using the National Health Insurance Research Database (NHIRD) from January 2001 to December 2015, we assessed the impact of this catch-up program by interrupted time-series analyses age-stratified (0-1, 2-4, 5-9, 10-17, 18-34, 35-49, 50-64, 65 + years old) incidence of pneumococcal pneumonia and all-cause pneumonia (100,000 person-quarter) among the overall and high-risk populations. RESULTS: The impact of this program was most profound on the incidence of pneumococcal pneumonia in children aged 2-4 years old (level change -10.56 per 100,000 person-quarters, p = 0.04; trend change -2.93, p less than 0.01). Indirect protection among unvaccinated children (0-1 years old: trend change -1.19, p = 0.01; 5-9 years old: trend change -1.04, p = 0.03; 10-17 years old: level change -1.42 per 100,000 person-quarters, p = 0.03) was also found. The incidence of all-cause pneumonia also decreased in children aged 2-4 (level change -234.91 per 100,000 person-quarter, p = 0.058) and 5-9 years old (level change -173.96 per 100,000 person-quarter, p = 0.0424). However, we did not find a significant impact among most high-risk populations. CONCLUSIONS: Our study suggests that the introduction of this catch-up program with PCV13 was associated with significant declines in the incidence of pneumococcal pneumonia and all-cause pneumonia in vaccinated children, and indirect protection from the program was also found in unvaccinated children.

An outbreak of human Rhinovirus-A21 infection in a psychiatric ward during COVID-19 pandemic.

A cluster of acute respiratory illnesses involving 12 inpatients and 3 healthcare workers occurred in a psychiatric ward. Eight of them were identified as HRV-A21. Fever and cough were the most common symptoms. The study also provides further evidence of the impact of HRV on lower respiratory tract illness.

Anti-Spike Antibody Response to Natural Infection with SARS-CoV-2 and Its Activity against Emerging Variants.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially affected human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2 infection. Here, we examined serological anti-spike antibody and memory B cell responses in adults with acute SARS-CoV-2 infection. Twenty-five adult patients were enrolled between January and September 2020, and 21 (84%) had a detectable spike-binding antibody response in serum on day 21 ± 8 (6 to 33) after the onset of illness. Among those with positive spike-binding antibody response, 19 (90%) had a positive hemagglutination titer and 15 (71%) had angiotensin-converting enzyme 2 (ACE2)-blocking serological activities. Follow-up serum samples collected 11 ± 1 (7 to 15) months after infection exhibited an average of 2.6 ± 1.0 (1.0 to 3.5)-fold reduction in the spike-binding antibody response. Moreover, convalescent and follow-up serum samples showed 83 ± 82 (15 to 306)- and 165 ± 167 (12 to 456)-fold reductions in the neutralization activity against the Omicron variant, respectively. Upon acute infection, spike-specific memory B cell responses were elicited, with an average frequency of 1.3% ± 1.2% of peripheral B cells on day 19 ± 7 (6 to 33) after the onset of illness. IgM memory B cells were predominantly induced. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In conclusion, spike-specific antibody response elicited upon acute SARS-CoV-2 infection may wane over time and be compromised by the emergence of viral variants. IMPORTANCE As spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In particular, spike-specific antibody response in the convalescent and follow-up serum samples was substantially affected by emerging variants, especially Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Effectiveness of case isolation and class suspension in mitigation of enterovirus transmission in children.

BACKGROUND: Appropriate mitigation strategy to minimize enterovirus (EV) transmission among children is essential to control severe EV epidemics. Scientific evidence for the effectiveness of case isolation and class suspension is lacking. METHODS: EV-infected children ≤ eight years are asked to stay at home for seven days. Classes were suspended for seven days if there are more than two classmates having an onset of herpangina or hand, foot, and mouth disease in one classroom within one week. Study subjects are divided into two groups, group A with class suspension for one week and group B without class suspension. RESULTS: Among 4153 reported EV-infected children from 1085 classes in May and June, 2015 were enrolled. Median incidence of EV infection in a class was 7% (range 3% -60%). The incidence was higher in group A (median 14%, range 3-60%) than that in group B (median 6%, range 3-80%) (P < 0.01). The median incidence is highest in day care center (20%), followed by kindergarten (8%), and primary school (4%) (P < 0.01). Most secondary cases in group A appeared within seven days after the disease onset of index case in the same class. The incidence of EV infection remained low and was similar between the two groups eight days and beyond after the disease onset of index cases. CONCLUSIONS: Targeted class suspension for seven days with case isolation for seven days is an effective measure to mitigate transmission of EV infection in children.

Using Machine Learning to Develop and Validate an In-Hospital Mortality Prediction Model for Patients with Suspected Sepsis.

BACKGROUND: Early recognition of sepsis and the prediction of mortality in patients with infection are important. This multi-center, ED-based study aimed to develop and validate a 28-day mortality prediction model for patients with infection using various machine learning (ML) algorithms. METHODS: Patients with acute infection requiring intravenous antibiotic treatment during the first 24 h of admission were prospectively recruited. Patient demographics, comorbidities, clinical signs and symptoms, laboratory test data, selected sepsis-related novel biomarkers, and 28-day mortality were collected and divided into training (70%) and testing (30%) datasets. Logistic regression and seven ML algorithms were used to develop the prediction models. The area under the receiver operating characteristic curve (AUROC) was used to compare different models. RESULTS: A total of 555 patients were recruited with a full panel of biomarker tests. Among them, 18% fulfilled Sepsis-3 criteria, with a 28-day mortality rate of 8%. The wrapper algorithm selected 30 features, including disease severity scores, biochemical parameters, and conventional and few sepsis-related biomarkers. Random forest outperformed other ML models (AUROC: 0.96; 95% confidence interval: 0.93-0.98) and SOFA and early warning scores (AUROC: 0.64-0.84) in the prediction of 28-day mortality in patients with infection. Additionally, random forest remained the best-performing model, with an AUROC of 0.95 (95% CI: 0.91-0.98, p = 0.725) after removing five sepsis-related novel biomarkers. CONCLUSIONS: Our results demonstrated that ML models provide a more accurate prediction of 28-day mortality with an enhanced ability in dealing with multi-dimensional data than the logistic regression model.

Investigating Unfavorable Factors That Impede MALDI-TOF-Based AI in Predicting Antibiotic Resistance.

The combination of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) spectra data and artificial intelligence (AI) has been introduced for rapid prediction on antibiotic susceptibility testing (AST) of Staphylococcus aureus. Based on the AI predictive probability, cases with probabilities between the low and high cut-offs are defined as being in the "grey zone". We aimed to investigate the underlying reasons of unconfident (grey zone) or wrong predictive AST. In total, 479 S. aureus isolates were collected and analyzed by MALDI-TOF, and AST prediction and standard AST were obtained in a tertiary medical center. The predictions were categorized as correct-prediction group, wrong-prediction group, and grey-zone group. We analyzed the association between the predictive results and the demographic data, spectral data, and strain types. For methicillin-resistant S. aureus (MRSA), a larger cefoxitin zone size was found in the wrong-prediction group. Multilocus sequence typing of the MRSA isolates in the grey-zone group revealed that uncommon strain types comprised 80%. Of the methicillin-susceptible S. aureus (MSSA) isolates in the grey-zone group, the majority (60%) comprised over 10 different strain types. In predicting AST based on MALDI-TOF AI, uncommon strains and high diversity contribute to suboptimal predictive performance.