Implication of genotypes for prognosis of Candida glabrata bloodstream infections.

BACKGROUND: Genotyping isolates of a specific pathogen may demonstrate unique patterns of antimicrobial resistance, virulence or outcomes. However, evidence for genotype-outcome association in Candida glabrata is scarce. We aimed to characterize the mycological and clinical relevance of genotypes on C. glabrata bloodstream infections (BSIs). METHODS: Non-duplicated C. glabrata blood isolates from hospitalized adults were genotyped by MLST, and further clustered by the unweighted pair group method with arithmetic averages (UPGMA). A clonal complex (CC) was defined by UPGMA similarities of >90%. Antifungal susceptibility testing was performed by a colorimetric microdilution method and interpreted following CLSI criteria. RESULTS: Of 48 blood isolates evaluated, 13 STs were identified. CC7 was the leading CC (n = 14; 29.2%), including 13 ST7. The overall fluconazole and echinocandin resistance rates were 6.6% and 0%, respectively. No specific resistance patterns were associated with CC7 or other CCs. Charlson comorbidity index (adjusted OR, 1.49; 95% CI, 1.05-3.11) was the only predictor for CC7. By multivariable Cox regression analyses, CC7 was independently associated with 28 day mortality [adjusted HR (aHR), 3.28; 95% CI, 1.31-8.23], even after considering potential interaction with neutropenia (aHR, 3.41; 95% CI, 1.23-9.42; P for interaction, 0.24) or limited to 34 patients with monomicrobial BSIs (aHR, 2.85; 95% CI, 1.15-7.08). Also, the Kaplan-Meier estimate showed greater mortality with CC7 (P = 0.003). Fluconazole resistance or echinocandin therapy had no significant impact on mortality. CONCLUSIONS: Our data suggested comorbid patients were at risk of developing CC7 BSIs. Further, CC7 was independently associated with worse outcomes.

Achievements of COVID-19 vaccination programs: Taiwanese perspective.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis. The specific characteristics of aerosol transmission in the latent period and the contagiousness of SARS-CoV-2 lead to rapid spread of infection in the community. Vaccination is the most effective method for preventing infection and severe outcomes. As of December 1, 2022, 88% of the Taiwanese population had received at least two doses of COVID-19 vaccines. Heterologous vaccination with ChAdOx1-mRNA-based or ChAdOx1-protein-based vaccines has been found to elicit higher immunogenicity than homologous vaccination with ChAdOx1-ChAdOx1 vaccines. A longitudinal cohort study revealed that 8-12-week intervals between the two heterologous vaccine doses of the primary series led to good immunogenicity and that the vaccines were safe. A third booster dose of mRNA vaccine is being encouraged to evoke effective immune responses against variants of concern. A novel domestic recombinant protein subunit vaccine (MVC-COV1901) was manufactured and authorized for emergency use in Taiwan. It has shown a good safety profile, with promising neutralizing antibody titers against SARS-CoV-2. Given the global pandemic due to emerging novel variants of SARS-CoV-2, booster COVID-19 vaccines and appropriate intervals between booster doses need to be investigated.

CT findings of 144 in-hospital patients with influenza pneumonia: A retrospective analysis.

BACKGROUND/PURPOSE: Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations. METHODS: In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores. RESULTS: The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73 ± 6.29 vs 12.49 ± 6.69 vs 18.94 ± 4.57, p < 0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02 ± 7.27 vs 8.95 ± 5.99, p < 0.05). CONCLUSION: Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia.

Immunogenicity and safety of heterologous booster with protein-based COVID-19 vaccine (NVX-CoV2373) in healthy adults: A comparative analysis with mRNA vaccines.

BACKGROUND: Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limited. We investigated the immunogenicity and adverse events of NVX-CoV2373 as a second booster and compared them with those of mRNA vaccines in healthy adults. METHODS: Healthcare workers who had received an mRNA vaccine (mRNA-1273 or BNT-162b2) as the first booster (third dose) 12 weeks prior were recruited. Participants voluntarily received either NVX-CoV2373 or an mRNA vaccine as a second booster. Participants with a history of SARS-CoV-2 infection were excluded. The primary outcomes included serum anti-SARS-CoV-2 spike protein (SP) and neutralizing antibody titers against B.1.1.7 (Alpha), B.1.1.529 (Omicron) BA2, and BA5 variants on the 28th day after the boost. Secondary outcomes included new SARS-CoV-2 infections and adverse events reported during the study period. RESULTS: A total of 160 participants were enrolled in this study. Compared with the mRNA vaccination group (n = 59), the NVX-CoV2373 vaccination group (n = 101) had significantly lower anti-SARS-CoV-2 SP antibody titers and neutralizing antibody titers against all variants tested after the boost. During the study period, higher rates of new SARS-CoV-2 infections and a lower incidence of adverse events were observed in the NVX-CoV2373 vaccination group. No significant differences in cellular immune responses were observed between the two groups. CONCLUSION: Compared to a homologous mRNA booster vaccination, heterologous boosters with NVX-CoV2373 showed lower antibody responses, a higher incidence of new SARS-CoV-2 infections, and fewer adverse events.

COVID-19 vaccination: 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) consensus statements.

The COVID-19 pandemic remains challenging due to the rapid evolution of the severe acute respiratory syndrome coronavirus 2. This article discusses recent findings on high-risk groups for COVID-19 mortality and morbidity, along with consensus statements from the 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) meeting. It examines evidence on viral mutation mechanisms, emerging variants, and their implications for vaccination strategies. The article underscores advanced age, immunocompromised status, chronic medical conditions, occupational exposure, and socioeconomic disparities as significant risk factors for severe COVID-19 outcomes. TAGG's consensus emphasizes robust vaccination promotion, prioritizing elderly, and immunocompromised groups, individualized multi-dose regimens for immunocompromised patients, and simplified clinical guidelines. Discussions on global and regional recommendations for regular, variant-adapted boosters highlight the non-seasonal nature of COVID-19. Key agreements include escalating domestic preparedness, implementing vigorous risk-based vaccination, and adapting global guidelines to local contexts. Given ongoing viral evolution, proactive adjustment of vaccination policies is essential. Scientific consensus, tailored recommendations, and rapid knowledge dissemination are vital for optimizing COVID-19 protection among vulnerable groups in Taiwan. This article seeks to inform clinical practice and public health policy by summarizing expert-driven vaccination perspectives.

Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Impact of an integrated medication management model on the collaborative working relationship among healthcare professionals in a hospital: an explanatory mixed methods study.

An integrated medication management (IMM) model was implemented in a medical center ward to improve the delivery of clinical pharmaceutical services (CPSs). This model incorporated a ward-based clinical pharmacist who performed medication reconciliation and medication reviews. It was perceived to promote interprofessional collaboration between pharmacists and non-pharmacist healthcare professionals (NPHPs, including attending physicians, nurse practitioners, and registered nurses). This study aimed to evaluate the effects of the IMM on NPHPs' intentions to collaborate with pharmacists and understand the mechanism of the impact of the IMM on interprofessional collaboration. A sequential explanatory mixed methods design was employed in the study. Initially, a questionnaire was administered to assess the effects of the IMM on NPHPs' intentions to collaborate with pharmacists. The NPHPs' experiences with the IMM were then documented using semi-structured interviews with inductive thematic analysis. Fifty-eight NPHPs completed the questionnaire, and NPHPs from the intervention ward reported a higher intention to discuss patient-related medication issues with pharmacists, indicating collaboration. Eleven NPHPs were interviewed, and they stated having better working relationships with pharmacists, experiencing more effective CPSs, and noting improved communication with pharmacists. The integration of quantitative and qualitative findings demonstrates that the critical mechanism of the IMM in promoting collaborative relationships is to integrate pharmacists into medical practice, which familiarizes NPHPs with pharmacists' roles, improves communication, and enables pharmacists to identify NPHPs' needs. To summarize, allowing ward-based pharmacists to engage in medical teams on a regular basis appears vital for improving interprofessional teamwork. Furthermore, stakeholders aiming to promote CPS in their institutions should consider the needs and communication channels among NPHPs.

Higher serologic responses of early syphilis to single-dose benzathine penicillin G plus doxycycline versus single-dose benzathine penicillin G alone among people with HIV.

BACKGROUND: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. METHODS: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a fourfold decline in RPR titers at month 12. RESULTS: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P= .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% CI, 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12. CONCLUSIONS: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.

CXCL9 as a Reliable Biomarker for Discriminating Anti-IFN-γ-Autoantibody-Associated Lymphadenopathy that Mimics Lymphoma.

The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.

Current practice and recommendations for management of hepatitis B virus in people living with HIV in Asia.

BACKGROUND: The prevalence of HIV and hepatitis B virus (HBV) co-infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. Important routes of transmission of both these infections include high-risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV-induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV. OBJECTIVES: This article describes the prevalence of co-infection, current clinical practice, and recommendations for the management of people living with HIV-HBV co-infection in Asia. RESULTS AND CONCLUSIONS: Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV-HBV co-infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co-infection rates. Mother-to-child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.

Readmission outcomes following infectious hospitalization: same-care unit performed better than different-care unit.

BACKGROUND: Previous studies showed that same-hospital readmission is associated with better outcomes than different-hospital readmission. However, little is known about whether readmission to the same care unit (same-care unit readmission) after infectious hospitalization performs better than readmission to a different care unit at the same hospital (different-care unit readmission). METHODS: This retrospective study screened patients rehospitalized within 30 days following admission to two acute medical wards for infectious diseases from 2013 to 2015 and included only those readmitted for unplanned medical reasons. Outcomes of interest included hospital mortality and length of stay of readmitted patients. RESULTS: Three hundred and fifteen patients were included; of those, 149(47%) and 166(53%) were classified as same-care unit and different-care unit readmissions, respectively. Same-care unit patients were more likely to be older(76 years vs. 70 years; P = 0.001), have comorbid chronic kidney disease(20% vs. 9%; P = 0.008), and have a shorter time to readmission(13 days vs. 16 days; P = 0.020) than different-care unit patients. Univariate analysis showed that same-care unit patients had a shorter length of stay than different-care unit patients(13 days vs. 18 days; P = 0.001), but had similar hospital mortality(20% vs. 24%; P = 0.385). The multivariable linear regression model indicated that same-care unit readmission was associated with a 5-day shorter hospital stay than different-care unit readmission(P = 0.002). CONCLUSION: Among patients readmitted within 30 days after hospitalization for infectious diseases, same-care unit readmission was associated with a shorter length of hospital stay than different-care unit readmission. Whenever feasible, it is encouraged to allocate a readmitted patient to the same care unit in hope of pursuing continuity and quality of care.

Serological response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 prime-boost vaccination with a twelve-week interval.

The appropriate interval between heterologous prime adenoviral vectored vaccination and boost mRNA vaccination remains unclear. We recruited 100 adult participants to receive a prime adenoviral vectored vaccine (ChAdOx1, AstraZeneca) and a boost mRNA vaccine (mRNA-1273, Moderna) 12 weeks apart and checked their serum SARS-CoV-2 anti-spike IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on the 28th day after the boost dose. Results were compared with our previous study cohorts who received the same prime-boost vaccinations at 4- and 8-week intervals. Compared to other heterologous vaccination groups, the 12-week interval group had higher neutralizing antibody titers against SARS-CoV-2 variants than the 4-week interval group and was similar to the 8-week interval group at day 28. Adverse reactions after the boost dose were mild and transient. Our results support deploying viral vectored and mRNA vaccines in a flexible schedule with intervals from 8 to 12 weeks.

Correlation of adverse effects and antibody responses following homologous and heterologous COVID19 prime-boost vaccinations.

BACKGROUND: Studies correlating reactogenicity and immunogenicity of COVID-19 vaccines are limited to BNT162b2, with inconsistent results. We investigated whether adverse reactions after other COVID-19 vaccines reliably predict humoral responses. METHODS: Adult volunteers were recruited for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines administered either 4 or 8 weeks apart. Adverse effects were routinely solicited and recorded by subjects in a standard diary card for up to 84 days post booster vaccination. Anti-SARS-CoV-2 IgG titers were measured pre- (visit 1), and post-booster dose at days 14 (visit 2) and 28 (visit 3). RESULTS: A total of 399 participants (75% women) with a median age of 41 (interquartile range, 33-48 IQR) years were included. Vaccine-induced antibody titers at days 14 and 28 were significantly higher among subjects who reported local erythema, swelling, pain, as well as systemic fever, chills, headache, myalgia, arthralgia, fatigue compared to those who did not experience local or systemic reactogenicity. Post-vaccination humoral responses did not correlate with the occurrence of skin rash and correlated weakly with gastrointestinal symptoms. A significant correlation between post-vaccination peak body temperature and anti-SARS-CoV-2 spike IgG at Day 14, independent of vaccine type and schedule, was found. CONCLUSION: Specific symptoms of reactogenicity such as post-vaccination injection site pain, swelling, erythema and fever, myalgia and fatigue are significantly predictive of the magnitude of the anti-SARS-CoV-2 antibody response.

Safety and antibody response of recipients who unexpectedly received undiluted prime dose of BNT162b2 COVID-19 vaccine in Taiwan.

We reported 25 recipients (14 females and 11 males) aged from 18 to 65 years who unexpectedly received a primary dose of undiluted BNT162b2 vaccine (180 µg). The most common adverse reactions included injection site pain (n = 22), followed by fever (9), fatigue (8), chest tightness (6), and dizziness (6). The most common laboratory abnormalities were anemia (n = 4) and elevated liver transaminase level (4), followed by abnormal leukocyte counts (3) and elevated D-dimer level (3). The adverse reactions and laboratory abnormalities of these recipients were mild and spontaneously recovered within a few weeks. Significant elevations of anti-SARS-CoV-2 spike IgG titers after a booster dose of the BNT162b2 were found. Similar to reports of BNT162b2 clinical trials, the adverse reactions and laboratory abnormalities of these recipients were mild, and they spontaneously recovered within a few weeks. These results provide clinical and immunological effects of undiluted BNT162b2 vaccine inoculation.

SARS-CoV-2 infection among healthcare workers whom already received booster vaccination during epidemic outbreak of omicron variant in Taiwan.

BACKGROUND/PURPOSE: Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan. METHODS: Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection. RESULTS: Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70-13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28-15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs. CONCLUSION: Community factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.

Immunogenicity and safety of third-dose mRNA COVID-19 vaccines in healthy adults previously vaccinated with two doses of the ChAdOx1 vaccine.

BACKGROUND/PURPOSE: The efficacy and safety of coronavirus disease 2019 (COVID-19) booster vaccines remain limited. We investigated the immunogenicity and adverse events of the third dose of mRNA vaccines in healthy adults. METHODS: Volunteers vaccinated with two doses of the adenoviral vaccine (ChAdOx1) 12 weeks before were administered with an mRNA COVID-19 vaccine. These were divided into three groups, full-dose mRNA-1273 (group 1); half-dose mRNA-1273 (group 2); and full-dose BNT-162b2 (group 3). Primary outcomes included serum anti-SARS-CoV-2 spike immunoglobulin G (IgG) titers and neutralizing antibody titers against B.1.1.7 (alpha), B.1.617.2 (delta), and B.1.1.529 (omicron) variants. Secondary outcomes included the evaluation of humoral and cellular immunity and vaccine-associated adverse events after the boost. RESULTS: Totally 300 participants were recruited, and 298 participants were enrolled. For all three groups, an increase in anti-SARS-CoV-2 spike IgG geometric mean titers (30.12- to 71.80-fold) and neutralizing antibody titers against the alpha variant (69.80- to 173.23-folds), delta variant (132.69- to 324.63-folds), and omicron variant (135.36- to 222.37-folds) were observed on day 28. All groups showed robust T- and B-cell responses after boosting. Adverse events were overall mild and transient but with higher prevalence and severity in group 1 participants than in other groups. CONCLUSION: Third dose mRNA COVID-19 vaccines markedly enhanced cellular and humoral responses and were safe. Immunological responses and adverse events were higher in individuals receiving the full-dose mRNA-1273 vaccine, followed by a half-dose mRNA-1273 vaccine and BNT-162b2 vaccine.

Viral dynamics of SARS-CoV-2 Omicron infections in a previously low COVID-19 prevalence region: Effects of vaccination status, antiviral agents, and age.

BACKGROUND: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. METHODS: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. RESULTS: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. CONCLUSION: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

Range-Extension Algorithms and Strategies for TDOA Ultra-Wideband Positioning System.

The Internet of Things (IoT) for smart industry requires the surveillance and management of people and objects. The ultra-wideband positioning system is an attractive solution for achieving centimeter-level accuracy in target location. While many studies have focused on improving the accuracy of the anchor coverage range, it is important to note that in practical applications, positioning areas are often limited and obstructed by furniture, shelves, pillars, or walls, which can restrict the placement of anchors. Furthermore, some positioning regions are located beyond anchor coverage, and a single group with few anchors may not be able to cover all rooms and aisles on a floor due to non-line-of-sight errors causing severe positioning errors. In this work, we propose a dynamic-reference anchor time difference of arrival (TDOA) compensation algorithm to enhance accuracy beyond anchor coverage by eliminating local minima of the TDOA loss function near anchors. We designed a multidimensional and multigroup TDOA positioning system with the aim of broadening the coverage of indoor positioning and accommodating complex indoor environments. By employing an address-filter technique and group-switching process, tags can seamlessly move between groups with a high positioning rate, low latency, and high accuracy. We deployed the system in a medical center to locate and manage researchers with infectious medical waste, demonstrating its usefulness for practical healthcare institutions. Our proposed positioning system can thus facilitate precise and wide-range indoor and outdoor wireless localization.

Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review.

BACKGROUND: Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course. METHODS: We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed. RESULTS: Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence. CONCLUSIONS: Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.