Objectives: To describe the immunological responses and clinical outcome of coronavirus (SARS) infected healthcare workers (HCW) who had been administered with convalescent plasma as a treatment. Methods: Convalescent plasma (500 mL) was obtained from each of three SARS patients and transfused into the three infected HCW. Donors were blood type O and seronegative for hepatitis B and C, HIV, syphilis and human T-cell lymphotropic virus types I and II (HTLV-I and -II). Serum antibody (IgG) titre was >640. Apharesis was performed with a CS 3000 plus cell separator followed by the forming of the convalescent phase plasma. As part of the routine check with donated plasma, the convalescent plasma was confirmed free of residual SARS-CoV by RT–PCR. Serial serum samples obtained from the recipients of the convalescent plasma were collected to undertake real-time quantitative RT–PCR for SARS-CoV for direct measurement of viral concentration. Specific immunoglobulin IgM and IgG concentrations were titrated using an antigen microarray developed in-house. Results: Viral load dropped from 495 × 10³, 76 × 10³ or 650 × 10³ copies/mL to zero or 1 copy/mL one day after transfusion. Anti-SARS-CoV IgM and IgG also increased in a time-dependent manner following transfusion. All three patients survived. One HCW became pregnant subsequently, delivering 13 months after discharge. Positive anti-SARS-CoV IgG was detected in the newborn. Passive transfer of anti-SARS-CoV antibody from the mother was considered as a possibility. Conclusions: All infected HCW whose condition had progressed severely and who had failed to respond to the available treatment, survived after transfusion with convalescent plasma.

Background. The Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins. Method. We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18–85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose. Results. No vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs. Conclusion. UB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines. Trial Registration. ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742. Funding. UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Background: Sustainable systematic interventions are important for infection prevention and control (IPC). Data from surveillance of healthcare-associated infections (HAI) provides feedback for implementation of IPC programs. To address the paucity of such data in Asia, we searched for national HAI surveillance and IPC programs in this region. Methods: Data were analysed from open access national surveillance reports of three Asian countries: Taiwan, South Korea and Japan from 2008 to 2015. National IPC programs were identified. Results: There were differences among the countries in surveillance protocols, hospital coverage rates, and national IPC policies and programs. Nevertheless, there was a 53.0% reduction in overall HAI over the 8-year period. This consisted of a decrease from 9.34 to 5.03 infections per 1000 patient-days in Taiwan, from 7.56 to 2.76 in Korea, and from 4.41 to 2.74 in Japan (Poisson regression, all p < 0.05). Across the three countries, Escherichia coli and Candida albicans were the major pathogens for urinary tract infection. Staphylococcus aureus, Acinetobacter baumannii and Enterococcus faecium were common bloodstream pathogens. For pneumonia, S. aureus, A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the predominant pathogens, with considerable country differences. There was a 64.6% decrease in the number of isolates of methicillin-resistant S. aureus, 38.4% decrease in carbapenem-resistant P. aeruginosa and 49.2% decrease in carbapenem-resistant A. baumannii (CRAB) in Taiwan (all p < 0.05), and similarly in Korea with the exception of CRAB (30.5 and 50.4% reduction, respectively, both p < 0.05). Conclusion: We found a significant decrease in HAI across the three countries in association with sequential multifaceted interventions such as hand hygiene, care bundles, and antimicrobial stewardships. Further regional collaboration could be forged to develop joint strategies to prevent HAI.

Since April 2022, another wave of the Omicron epidemic has struck Taiwanese society, and children with severe neurological complications have been reported frequently. A few cases even developed acute fulminant encephalitis. To investigate the possible causes of the increased incidence of such complications in Taiwan, we reviewed several cases of pediatric patients with severe neurological symptoms. We collected the medical records of pediatric patients with COVID-19 infection who presented with severe neurological symptoms. The COVID-19 infection was diagnosed by nasal swab reverse transcriptase-polymerase chain reaction. The remaining samples were sent for whole genome sequencing and spike (S) protein amino acid variation mapping. The increase of several inflammatory markers was observed in all patients included in this study. However, none of the cerebrospinal fluid samples tested positive for SARS-CoV-2. The result of whole genome sequencing showed that all the sequences belonged to the lineage BA.2.3.7. However, the sequences had a K97E mutation in the S protein that differed from other BA.2.3.7 lineage strains, which was located at the S protein N-terminal domain. The new mutation in the S protein, which had not previously been observed but was discovered in this study, potentially explains the sudden increase in incidence of extremely adverse neurological symptoms in pediatric patients.

Community-onset urinary tract infections (CoUTIs) are the most common bacterial infections, and a decline in antibiotic susceptibility causes many clinical challenges. Adequate empiric antibiotic treatment can decrease unnecessary hospital stays and complications, while reducing the antimicrobial resistance progression. From October 2014 to April 2015, we retrospectively enrolled patients who were at least 18 years old and required hospitalization for CoUTIs. Demographic variables of these patients, and uropathogens and their antimicrobial susceptibilities were evaluated. In total, 457 patients were enrolled in this study. Their mean age was 71.9 years, and 35.2% of the patients were male. Escherichia coli (54.5%) was the most common uropathogen, followed by Klebsiella pneumoniae (13.1%), Enterococcus spp. (7.1%), Pseudomonas aeruginosa (4.6%), and Proteus mirabilis (3.5%). Bacteremia was present in 25.2% of patients. Diabetes mellitus and acute kidney injury at admission were risk factors for CoUTIs with concomitant bacteremia. Among the UTI-associated bloodstream strains, E. coli (53.1%) was also the most predominant pathogen, followed by K. pneumoniae (11.3%), Staphylococcus aureus (6.1%), and P. mirabilis (4.3%). The overall susceptibility of cefazolin was 62.8%, ceftriaxone 71.4%, ceftazidime 82.8%, flomoxef 82%, cefepime 94.5%, ampicillin-sulbactam 41.6%, piperacillin-tazobactam 85%, levofloxacin 65.2%, trimethoprim-sulfamethoxazole 61.5%, imipenem 92.3%, gentamicin 76.1%, and amikacin 97.5%. Cefazolin-susceptible isolates could be found more frequently among patients who are less than 65 years of age and without diabetes mellitus, had no UTI episode in the past year, and have no bacteremia risk. Patients with nasogastric tube retention more commonly experienced antimicrobial resistance to all the third-generation cephalosporins. Third-generation cephalosporins effectively treated CoUTIs. However, patients with nasogastric tube retention more commonly experienced cephalosporin resistance. Cefepime, imipenem, and amikacin may be used in patients with higher antimicrobial resistance. In selected patients, cefazolin may still be an adequate drug of choice for CoUTIs.

In Asia, serotype K1/K2 Klebsiella pneumoniae are the major capsular serotypes that cause liver abscess or bacteremia in patients. The purpose of this study was to compare novel immunochromatographic strips (ICSs), which can rapidly detect K. pneumoniae serotypes K1/K2 in clinical samples, to conventional capsular serotyping methods. Pus drainage samples from 16 patients with a liver abscess caused by K. pneumoniae, blood samples from 112 positive flagged blood culture bottle and a subsequent single colony in the medium were tested with the ICS. The results were then compared to findings of capsular swelling tests. Samples subjected to the polymerase chain reaction (PCR) analysis were used as reference. The identification of K. pneumoniae via the traditional bacterial culture from pus samples took 3.4 days on average (ranging from 2.2 to 5.5 days). Further capsular serotyping of K. pneumoniae by the capsular swelling test of pure isolates lasted 5–10 min, and the PCR method took ~ 4 h. As for ICSs, the time for direct identification of the K. pneumoniae capsular serotype K1/K2 in pus was < 4 min (ranging from 2 to 4 min). The results of ICSs were consistent with capsular swelling tests and PCR methods. Testing of 112 blood culture samples and subsequent single colonies in the medium with ICSs yielded consistent results for most samples. This study indicates that ICSs can rapidly detect K. pneumoniae serotypes K1 and K2 in pus or positive flagged blood culture broth samples within 5 min. Their accuracy is comparable to that of the conventional capsular serotyping methods such as a serum agglutination assay or PCR.