From Blur to Brilliance: The Ascendance of Advanced Microscopy in Neuronal Cell Biology.

The intricate network of the brain's neurons and synapses poses unparalleled challenges for research, distinct from other biological studies. This is particularly true when dissecting how neurons and their functional units work at a cell biological level. While traditional microscopy has been foundational, it was unable to reveal the deeper complexities of neural interactions. However, an imaging renaissance has transformed our capabilities. Advancements in light and electron microscopy, combined with correlative imaging, now achieve unprecedented resolutions, uncovering the most nuanced neural structures. Maximizing these tools requires more than just technical proficiency. It is crucial to align research aims, allocate resources wisely, and analyze data effectively. At the heart of this evolution is interdisciplinary collaboration, where various experts come together to translate detailed imagery into significant biological insights. This review navigates the latest developments in microscopy, underscoring both the promise of and prerequisites for bending this powerful tool set to understanding neuronal cell biology.

Effects of healthy aging and mnemonic strategies on verbal memory performance across the adult lifespan: Mediating role of posterior hippocampus.

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.

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.

Robust, Reproducible, and Scalable Synthesis of Silver Nanocubes.

It remains a challenge to accomplish colloidal synthesis of noble-metal nanocrystals marked by high quality, large quantity, and batch-to-batch consistency. Here we report a self-airtight setup for achieving robust, reproducible, and scalable production of Ag nanocubes with uniform and controlled sizes from 18 to 60 nm. Different from the conventional open-to-air setup, the self-airtight system makes it practical to stabilize the reaction condition by minimizing the loss of volatile reagents. The new setup also allows us to easily optimize the amount of O2 (from air) trapped in the system, ensuring burst nucleation of single-crystal seeds, followed by their slow growth into nanocubes. Most significantly, the new setup allows for the production of Ag nanocubes at gram quantities without sacrificing uniformity, corner/edge sharpness, controlled size, and high purity across different batches. The availability of high-quality Ag nanocubes in such a large quantity is anticipated to substantially boost their use in applications related to plasmonics, catalysis, and biomedicine.

The incidences and clinical outcomes of cryptococcosis in Taiwan: A nationwide, population-based study, 2002-2015.

Large-scale epidemiological data on cryptococcosis other than cryptococcal meningitis (CM), human immunodeficiency virus (HIV)- or solid organ transplantation (SOT)-associated cryptococcosis are limited. This study investigated the disease burden of cryptococcosis in Taiwan over 14 years. Incident episodes of cryptococcosis, comorbidities, treatment, and outcomes were captured from Taiwan's National Health Insurance Research Database and National Death Registry between 2002 and 2015. Of 6647 episodes analyzed, the crude incidence rate per 100 000 population increased from 1.48 in 2002 to 2.76 in 2015, which was driven by the growing trend in the non-CM group (0.86-2.12) but not in the CM group (0.62-0.64). The leading three comorbidities were diabetes mellitus (23.62%), malignancy (22.81%), and liver disease (17.42%). HIV accounted for 6.14% of all episodes and was associated with the highest disease-specific incidence rate (269/100 000 population), but the value dropped 16.20% biennially. Within 90 days prior to cohort entry, 30.22% of episodes had systemic corticosteroid use. The in-hospital mortality of all episodes was 10.80%, which varied from 32.64% for cirrhosis and 13.22% for HIV to 6.90% for SOT. CM was associated with a higher in-hospital mortality rate than non-CM (19.15% vs. 6.33%). At diagnosis, only 48.53% of CM episodes were prescribed an amphotericin-based regimen. The incidence rate of cryptococcosis was increasing, especially that other than meningitis and in the non-HIV population. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality in populations other than those with HIV infection or SOT.

This nationwide study showed that the incidence rate of cryptococcosis doubled from 2002 to 2015. Non-meningeal cryptococcosis and non-HIV/nontransplant (NHNT)-associated cryptococcosis contributed to this increase. Our study highlighted the underestimated burden of cryptococcosis in the NHNT hosts.

Feasibility of Auto-Quantified Epicardial Adipose Tissue in Predicting Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: The aim of this study was to build an auto-segmented artificial intelligence model of the atria and epicardial adipose tissue (EAT) on computed tomography (CT) images, and examine the prognostic significance of auto-quantified left atrium (LA) and EAT volumes for AF.Methods and Results: This retrospective study included 334 patients with AF who were referred for catheter ablation (CA) between 2015 and 2017. Atria and EAT volumes were auto-quantified using a pre-trained 3-dimensional (3D) U-Net model from pre-ablation CT images. After adjusting for factors associated with AF, Cox regression analysis was used to examine predictors of AF recurrence. The mean (±SD) age of patients was 56±11 years; 251 (75%) were men, and 79 (24%) had non-paroxysmal AF. Over 2 years of follow-up, 139 (42%) patients experienced recurrence. Diabetes, non-paroxysmal AF, non-pulmonary vein triggers, mitral line ablation, and larger LA, right atrium, and EAT volume indices were linked to increased hazards of AF recurrence. After multivariate adjustment, non-paroxysmal AF (hazard ratio [HR] 0.6; 95% confidence interval [CI] 0.4-0.8; P=0.003) and larger LA-EAT volume index (HR 1.1; 95% CI 1.0-1.2; P=0.009) remained independent predictors of AF recurrence. CONCLUSIONS: LA-EAT volume measured using the auto-quantified 3D U-Net model is feasible for predicting AF recurrence after CA, regardless of AF type.

Practice and Effect Evaluation of Preoperative Management Strategy for Patients Undergoing Day Arthroscopic Surgery Based on Evidence-Based Concept.

Objective: To improve the preoperative management of patients undergoing day arthroscopy. Methods: Based on the evidence-based concept, the preoperative management strategy of daytime arthroscopic surgery was practiced, and the implementation effect of patients undergoing daytime arthroscopic surgery before and after evidence application was compared. The evidence-based strategies adopted in this study include: informed consent,seven aspects: anesthesia assessment, health education, prohibition of drinking and eating, preoperative medication guidance, surgical arrangement, and emergency management. Results: After applying evidence-based strategies, significant improvements were observed in various quality indicators, including reduced waiting time, reduced surgical cancellations, increased patient satisfaction, and reduced unplanned hospitalization rates. Conclusion: Based on the evidence-based concept, the practice of preoperative management strategies for patients undergoing daytime arthroscopic surgery optimizes the daytime surgical process from the strict implementation of patient health education and evaluation, as well as the establishment of compliant and reasonable surgical schedules and emergency mechanisms. This improves the preoperative management behavior of daytime surgery, enhances the patient's medical experience, and enhances the quality of daytime surgical care, providing a good basis for management and decision-making.

Environment contamination and intra-hospital spread of COVID-19 in a tertiary care Hospital in Taiwan.

BACKGROUND: The role of environmental contamination in COVID-19 transmission within hospitals is still of interest due to the significant impact of outbreaks globally. However, there is a scarcity of data regarding the utilization of environmental sampling for informing infection control measures during SARS-CoV-2 outbreaks. METHODS: This retrospective study analyzed incident event investigations conducted at a single center from May 1, 2021, to August 31, 2021. Investigations were initiated following the identification of a COVID-19 confirmed case (referred to as the index case) who had stayed in a hospital area outside the dedicated COVID-19 ward/bed and without specific COVID-19 precautions. Measures to prevent intra-hospital spread included contact tracing, adjusted testing policies, isolation of confirmed cases, quarantine of close contacts, environmental disinfection, and PCR testing of environmental samples. RESULTS: Among the 18 incident events investigated, the index case was a healthcare personnel in 8 events, a patient in 8 events, and a caregiver in 2 events. The median number of confirmed COVID-19 cases within 14 days was 13 (IQR, 7-31) for events with SARS-CoV-2 RNA detected on environmental surfaces, compared to only one (IQR, 1-1.5) for events without surface contamination (P = 0.04). Environmental contamination was independently associated with a higher number of COVID-19 cases (P < 0.001). CONCLUSION: This study highlights environmental contamination as an indicator of the severity of incident events and provides a framework for incident event management, including a protocol for environmental sampling. Implementing these measures can help prevent the spread of COVID-19 within healthcare facilities.

Serological responses to COVID-19 vaccination in patients with chronic liver diseases.

Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti-SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses.

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.

A Randomized Clinical Trial of 1-Dose vs Accelerated 2-Dose Schedule for Hepatitis A Virus (HAV) Revaccination Among People With Human Immunodeficiency Virus Who Were Nonresponders or Had Seroreversion After Primary HAV Vaccination.

BACKGROUND: For people with human immunodeficiency virus (PWH) who have no serological responses to their primary hepatitis A virus (HAV) vaccination or have seroreversion after successful primary vaccination, the optimal revaccination strategy remains unclear. METHODS: In this open-label, randomized clinical trial, PWH who tested negative for anti-HAV antibodies after receiving a standard 2-dose series of primary HAV vaccination were enrolled and assigned in a 1:1 ratio to receive either 1 dose (the 1-dose group) or 2 doses of HAV vaccine administered 4 weeks apart (the 2-dose group). Serological response rates and anti-HAV antibody titers were compared at weeks 24 and 48. RESULTS: Of the 153 participants (77 in the 1-dose group and 76 in the 2-dose group), the overall serological response rates at week 48 after revaccination were similar between the 2 groups (2- vs 1-dose, 80.2% vs 71.4%, P = .20). However, anti-HAV antibody titers were consistently higher in the 2-dose group than in the 1-dose group. In subgroup analysis, PWH who were nonresponders to primary HAV vaccination were significantly more likely to mount a serological response after 2-dose HAV revaccination (68.4% vs 44.1%, P = .038). No severe adverse events were reported throughout the study. CONCLUSIONS: Two-dose HAV revaccination administered 4 weeks apart yielded similar serological responses as 1-dose revaccination among PWH who were nonresponders or had seroreversion after primary HAV vaccination. The 2-dose revaccination schedule generated significantly higher anti-HAV antibody titers and was more likely to elicit serological responses at week 48 among PWH who were nonresponders to primary HAV vaccination. Clinical Trials Registration. NCT03855176.

Rapid Escherichia coli Cloned DNA Detection in Serum Using an Electrical Double Layer-Gated Field-Effect Transistor-Based DNA Sensor.

In this study, a rapid diagnosis platform was developed for the detection of Escherichia coli O157:H7. An electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) as a point-of-care testing device is demonstrated with its high sensitivity, portability, high selectivity, quick response, and ease of use. The specially designed ssDNA probe was immobilized on the extended gate electrode to bind the target complementary DNA segment of E. coli, resulting in a sharp drain current change within minutes. The limit of detection for target DNA is validated to a concentration of 1 fM in buffer solution and serum. Meanwhile, the results of a Kelvin probe force microscope were shown to have reduced surface potential of the DNA immobilized sensors before and after the cDNA detection, which is consistent with the decreased drain current of the BioFET. A 1.2 kb E. coli duplex DNA synthesized in plasmid was sonicated and detected in serum samples with the sensor array. Gel electrophoresis was used to confirm the efficiency of sonication by elucidating the length of DNA. Those results show that the EDL-gated BioFET system is a promising platform for rapid identification of pathogens for future clinical needs.

Comparison of Long-Term Clinical Outcomes Between Segmental and Circumferential Pulmonary Vein Isolation in Patients Undergoing Repeat Atrial Fibrillation Ablation.

BACKGROUND: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed. CONCLUSIONS: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.

Long non-coding RNAs in virus-related cancers.

Some viral infections lead to tumourigenesis explained by a variety of underlying molecular mechanisms. Long non-coding RNAs (lncRNAs) have the potential to be added to this list due to their diverse mechanisms in biological functions and disease processes via gene alternation, transcriptional regulation, protein modification, microRNA sponging and interaction with RNA/DNA/proteins. In this review, we summarise the dysregulation and mechanism of lncRNAs in virus-related cancers focussing on Hepatitis B virus, Epstein-Barr virus, Human Papillomavirus. We will also discuss the potential implications of lncRNAs in COVID-19.

Maternal risk factors in offspring with congenital anomalies of the kidney and urinary tract in Asian women.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of pediatric chronic kidney disease. Maternal body mass index (BMI) before pregnancy, pregestational diabetic mellitus (DM), and gestational diabetic mellitus (GDM) are potential modifiable risk factors for CAKUT in offspring. METHODS: In this case control study, 4619 neonates were enrolled during 2012-2020 from Kaohsiung Veterans General Hospital in Taiwan. Maternal risk factors before and during pregnancy were compared in children with and without CAKUT. The yearly incidence of CAKUT in offspring and maternal overweight were recorded. RESULTS: In total, 73 (1.6%) cases of CAKUT in offspring were identified. Maternal overweight before pregnancy (BMI ≥ 24 kg/m2) was an independent risk factor for CAKUT in offspring. No associations of pregestational DM and GDM with CAKUT in offspring were observed. The incidence rates of CAKUT and maternal obesity have increased in the past 10 years. CONCLUSIONS: Maternal obesity before pregnancy is associated with CAKUT in offspring and should be addressed to ensure better outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Applying the Integrated Sustainability Framework to explore the long-term sustainability of nutrition education programmes in schools: a systematic review.

OBJECTIVE: This review aimed to identify and synthesise the enablers and barriers that influence the long-term (≥ 2 years) sustainment of school-based nutrition programmes. DESIGN: Four databases (PubMed, Cochrane Library, Embase and Scopus) were searched to identify studies reporting on the international literature relating to food and nutrition programmes aimed at school-age (5-14 years) children that had been running for ≥ 2 years (combined intervention and follow-up period). Eligible studies were analysed using the Integrated Sustainability Framework (ISF), which involved deductive coding of programme enablers and barriers. A quality assessment was completed, using the Mixed-Methods Appraisal Tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. SETTING: International school-based nutrition programmes. SUBJECTS: Individuals involved with the implementation of school-based nutrition programmes. RESULTS: From the 7366 articles identified, thirteen studies (seven qualitative, five mixed methods and one quantitative descriptive) were included, from which the enablers and barriers of eleven different nutrition-related programmes were analysed. Thirty-four factors across the five domains of the ISF were identified that influenced the sustained implementation of programmes. The most common barrier was a lack of organisational readiness and resources, whereas the most common enabler was having adequate external partnerships and a supportive environment. CONCLUSIONS: These findings have application during the initiation and implementation phases of school-based nutrition programmes. Paying attention to the 'outer contextual factors' of the ISF including the establishment and maintenance of robust relationships across whole of government systems, local institutions and funding bodies are crucial for programme sustainment.

Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF.

In this study, fourteen celastrol derivatives (1-14) were synthesised by esterification of celastrol at the 29th position. The in vitro anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, with IC50 of the submicron molar level. The most promising compound (2) blocked the cell cycle in the G2 phase and inhibited the expression of VEGF and MMP-9 in gastric cancer cell line MGC-803. In flow cytometry analysis, compound 2 induced cancer cell apoptosis in a dose-dependent manner. In the mouse tumour xenograft model, compound 2 showed significant anti-tumour activity in vivo at the dosage of 2.5 mg/kg and 1 mg/kg, with a higher inhibition rate than 5-FU (10 mg/kg). What's more, the anticancer mechanism involved in the inhibition of VEGF and the toxicity evaluation of compound 2 were also investigated.

Subchronic exposure to PM2.5 induced renal function damage and intestinal microflora changes in rats.

BACKGROUND: Exposure to inhalable environmental particulate matter with a diameter of 2.5 µm or smaller (PM2.5) is associated with decreased or impaired kidney function, but the underlying biological mechanisms are not fully understood. Gut microbiota is an emerging key player in the homeostasis regulation of the gut-kidney axis. Few studies have investigated its role in PM2.5 exposure-induced gut-kidney axis homeostasis abnormalities. METHODS: In this study, a versatile aerosol concentration enrichment system for medium- to long-term whole-body exposure was used to expose Sprague-Dawley rats to filtered air (FA) or concentrated ambient PM2.5 for 12 weeks. A correlation analysis of renal impairment and the intestinal microbiome was performed. RESULTS: The urine flow rate calculation and renal function analysis showed that PM2.5 exposure significantly impaired renal function and increased the urine flow rate. The fecal microbiota analysis showed that renal impairment and increased urine flow rates were consistent with the reduced estimates of the fecal bacteria Chao1, observed-species, Shannon, and Simpson (richness and diversity indices). Pearson's correlation analysis showed that the estimated bacterial richness and diversity were correlated with the urine flow rate and renal function. The linear discriminant analysis effect size (LEfSe) analysis revealed differences between animals exposed to PM2.5 and FA in 25 bacterial groups. Further correlation of a single bacterial taxon with the urine flow rate and renal function showed that the relative abundances of 30, 29, 21, and 50 distinct bacterial groups were significantly correlated with the urine flow rate, estimated glomerular filtration rate (eGFR), serum cystatin C (CysC), and beta-2 microglobulin (ß2-MG), respectively. CONCLUSION: Subchronic exposure to PM2.5 can cause intestinal ecological disorders, which may, in turn, lead to decreased kidney function or the development of impaired kidney function.

Immunogenicity and safety of heterologous mRNA-1273/MVC-COV1901 vaccination versus homologous mRNA1273 vaccination: A randomized, double-blind controlled study.

BACKGROUND/PURPOSE: MVC-COV1901 is a protein vaccine based on the same SARS-CoV-2 strain used in mRNA vaccine mRNA-1273. Data are lacking on immunogenicity and safety of MVC-COV1901 as heterologous boost for people already received one dose of mRNA-1273. METHODS: This is a randomized, double-blind trial that recruited adults aged 20-70 years who previously received a single dose of mRNA-1273 vaccine and were randomly assigned in a 1:1 ratio to receive a second dose with the homologous vaccine or protein-based MVC-COV1901 8-12 weeks after the first dose. The primary outcome was neutralizing antibody titers in terms of the geometric mean titer (GMT) 14 days after the second dose. Safety was assessed in all participants who received a dose of the study vaccine. The study is registered with ClinicalTrials.gov (NCT05079633). RESULTS: From September 30 to November 5, 2021, 144 participants were enrolled and randomly assigned to the MVC-COV1901 boost group (n = 72) or the mRNA-1273 boost group (n = 72). The neutralizing antibodies on Day 15 and the anti-SARS-CoV-2 IgG titers on Day 15 and 29 of homologous mRNA-1273 were significantly higher than those of heterologous mRNA-1273/MVC-COV1901. Cellular immune responses were comparable in both groups. However, adverse events were much more frequent after the mRNA-1273 boost than after the MVC-COV1901 boost. CONCLUSION: Our results show that heterologous boost with MVC-COV1901 yielded an inferior immunogenicity but significantly fewer adverse events, compared with homologous boost with mRNA-1273. In people experienced severe adverse events after prime dose of mRNA-1273, as well as in periods when the supply of mRNA-1273 is limited, MVC-COV1901 could serve as an acceptable alternative heterologous boost.

Evolution of neutralizing antibodies and cross-activity against different variants of SARS-CoV-2 in patients recovering from COVID-19.

BACKGROUND: Patients recovering from COVID-19 may need vaccination against SARS-CoV-2 because acquired immunity from primary infection may wane, given the emergence of new SARS-CoV-2 variants. Understanding the trends of anti-spike IgG and neutralizing antibody titers in patients recovering from COVID-19 may inform the decision made on the appropriate interval between recovery and vaccination. METHODS: Participants aged 20 years or older and diagnosed with COVID-19 between January and December, 2020 were enrolled. Serum specimens were collected every three months from 10 days to 12 months after the onset of symptom for determinations of anti-spike IgG and neutralizing antibody titers against SARS-CoV-2 Wuhan strain with D614G mutation, alpha, gamma and delta variants. RESULTS: Of 19 participants, we found a decreasing trend of geometric mean titers of anti-spike IgG from 560.9 to 217 and 92 BAU/mL after a 4-month and a 7-month follow-up, respectively. The anti-spike IgG titers declined more quickly in the ten participants with severe or critical disease than the nine participants with only mild to moderate disease between one month and seven months after SARS-CoV-2 infection (-8.49 vs - 2.34-fold, p < 0.001). The neutralizing activity of the convalescent serum specimens collected from participants recovering from wild-type SARS-CoV-2 infection against different variants was lower, especially against the delta variants (p < 0.01 for each variant with Wuhan strain as reference). CONCLUSION: Acquired immunity from primary infection with SARS-CoV-2 waned within 4-7 months in COVID-19 patients, and neutralizing cross-activities against different SARS-CoV-2 variants were lower compared with those against wild-type strain.