Risk factors for SARS-CoV-2 transmission during a movie theater outbreak in Incheon in the Republic of Korea, November 2021: a retrospective study.

BACKGROUND: We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. METHODS: This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. RESULTS: Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARSCoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37-78.39) than casual contacts. CONCLUSION: SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters.

A collection of 157 individual neuromelanin-sensitive images accompanied by non-linear neuromelanin-sensitive atlas and a probabilistic locus coeruleus atlas.

The current dataset aims to support and enhance the research reliability of neuromelanin regions in the brainstem, such as locus coeruleus (LC), by offering raw neuromelanin-sensitive images. The dataset includes raw neuromelanin-sensitive images from 157 healthy individuals (8-64 years old). In addition, leveraging individual neuromelanin-sensitive images, a non-linear neuromelanin-sensitive atlas, generated through an iterative warping process, is included to tackle the common challenge of a limited field of view in neuromelanin-sensitive images. Finally, the dataset encompasses a probabilistic LC atlas generated through a majority voting approach with pre-existing multiple atlas-based segmentations. This process entails warping pre-existing atlases onto individual spaces and identifying voxels with a majority consensus of over 50 % across the atlases. This LC probabilistic atlas can minimize uncertainty variance associated with choosing a specific single atlas.

Changes in the intrinsic severity of severe acute respiratory syndrome coronavirus 2 according to the emerging variant: a nationwide study from February 2020 to June 2022, including comparison with vaccinated populations.

BACKGROUND: As the population acquires immunity through vaccination and natural infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the intrinsic severity of coronavirus disease (COVID-19) is becoming challenging. We aimed to evaluate the intrinsic severity regarding circulating variants of SARS-CoV-2 and to compare this between vaccinated and unvaccinated individuals. METHODS: With unvaccinated and initially infected confirmed cases of COVID-19, we estimated the case severity rate (CSR); case fatality rate (CFR); and mortality rate (MR), including severe/critical cases and deaths, stratified by age and compared by vaccination status according to the period regarding the variants of COVID-19 and vaccination. The overall rate was directly standardized with age. RESULTS: The age-standardized CSRs (aCSRs) of the unvaccinated group were 2.12%, 5.51%, and 0.94% in the pre-delta, delta, and omicron period, respectively, and the age-standardized CFRs (aCFRs) were 0.60%, 2.49%, and 0.63% in each period, respectively. The complete vaccination group had lower severity than the unvaccinated group over the entire period showing under 1% for the aCSR and 0.5% for the aCFR. The age-standardized MR of the unvaccinated group was 448 per million people per month people in the omicron period, which was 11 times higher than that of the vaccinated group. In terms of age groups, the CSR and CFR sharply increased with age from the 60 s and showed lower risk reduction in the 80 s when the period changed to the omicron period. CONCLUSIONS: The intrinsic severity of COVID-19 was the highest in the delta period, with over 5% for the aCSR, whereas the completely vaccinated group maintained below 1%. This implies that when the population is vaccinated, the impact of COVID-19 will be limited, even if a new mutation appears. Moreover, considering the decreasing intrinsic severity, the response to COVID-19 should prioritize older individuals at a higher risk of severe disease.

Three distinct ORF1a recombinants of the SARS-CoV-2 Delta variant of concern.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergency of various lineages through mutations and recombination. In the Delta lineage, we identified recombination events in the ORF1a gene, which divided the Delta sublineages into three different genotypes (Delta R1-R3). The regional distributions of Delta R1 and Delta R2 were not correlated, indicating that recombination occurred early in the Delta outbreak. The impact of the ORF1a gene on SARS-CoV-2 transmission remains unclear; however, our findings suggest that recombination may have contributed to the evolution and global spread of the Delta lineage.

Neutralization Testing-based Immunogenicity Analysis of Recent Prevalent Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Sublineages.

Although WHO declared the end of the public health emergency for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), XBB lineages continue to evolve and emerge globally. In particular, XBB.1.5 and XBB.1.16 are raising concerns because of their high immune evasion, leading to apprehensions regarding vaccine efficacy reduction and potential reinfection. We aimed to investigate the COVID-19 outbreak in Korea and predict the likelihood of reinfection by testing neutralizing activity against live viruses from the S clade and 19 Omicron sublineages. We found a significant risk of infection with the currently prevalent XBB lineage for individuals who were either vaccinated early or infected during the initial Omicron outbreak. Vaccinated individuals were better equipped than unvaccinated individuals to produce neutralizing antibodies for other SARS-CoV-2 variants upon infection. Therefore, unvaccinated individuals do not easily develop neutralizing activity against other variants and face the highest risk of reinfection by the XBB lineage. Our study provides important information to facilitate the development of strategies for monitoring populations that would be the most susceptible to new COVID-19 outbreaks.

The Lrp transcriptional factor of an entomopathogenic bacterium, Xenorhabdus hominickii, activates non-ribosomal peptide synthetases to suppress insect immunity.

Two bacterial genera, Xenorhabdus and Photorhabdus, are mutually symbiotic to the entomopathogenic nematodes, Steinernema and Heterorhabditis, respectively. The infective juveniles deliver the symbiotic bacteria to the hemocoel of target insects, in which the bacteria proliferate and help the development of the host nematode. The successful parasitism of the nematode-bacterial complex depends on host immunosuppression by the bacteria via their secondary metabolites. Leucine-responsive regulatory protein (Lrp) is a global bacterial transcriptional factor that plays a crucial role in parasitism. However, its regulatory targets to suppress insect immunity are not clearly understood. This study investigated the bacterial genes regulated by Lrp and the subsequent production of secondary metabolites in Xenorhabdus hominickii. Lrp expression occurred at the early infection stage of the bacteria in a target insect, Spodoptera exigua. A preliminary in silico screening indicated that 3.7% genes among 4075 predicted genes encoded in X. hominickii had the Lrp-response element on their promoters, including two non-ribosomal peptide synthetases (NRPSs). Eight NRPS (NRPS1-NRPS8) genes were predicted in the bacterial genome, in which six NRPS (NRPS3-NRPS8) expressions were positively correlated with Lrp expression in the infected larvae of S. exigua. Exchange of the Lrp promoter with an inducible promoter altered the production of the secondary metabolites and the NRPS expression levels. The immunosuppressive activities of X. hominickii were dependent on the Lrp expression level. The metabolites produced by Lrp expression included the eicosanoid-biosynthesis inhibitors and hemolytic factors. A cyclic dipeptide (=cPF) was produced by the bacteria at high Lrp expression and inhibited the phospholipase A2 activity of S. exigua in a competitive inhibitory manner. These results suggest that Lrp is a global transcriptional factor of X. hominickii and plays a crucial role in insect immunosuppression by modulating NRPS expression.

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04).

PURPOSE: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. MATERIALS AND METHODS: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). RESULTS: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm. CONCLUSION: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

Dermoscopic and Histopathologic Analysis of the Correlation between the Pigmentation of Basal Cell Carcinoma and Tumor Aggressiveness.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer. In patients with darker skin, most BCCs are pigmented. Studies suggest that increased pigmentation in BCC may be inversely associated with tumor aggressiveness. OBJECTIVE: This study analyzed the dermoscopic features and histopathologic patterns of BCCs to evaluate the correlation between BCC pigmentation and tumor aggressiveness. METHODS: A total of 76 BCC lesions were included in this retrospective study. The Mohs micrographic surgery (MMS) stage and tumor depth were measured as indices of tumor aggressiveness. The Fontana-Masson stain was performed for the identification of melanin, and immunohistochemical analysis was performed using Melan-A and HMB-45 to identify melanocytes. RESULTS: In MMS stage 1, the dermoscopic pigmentation value was 34.48%±14.22% (mean±standard deviation). In MMS stages 2 and 3, dermoscopic pigmentations were 13.72%±7.54% and 15.50%±17.52%, respectively. In the logistic regression model, higher dermoscopic pigmentation (95% confidence interval [CI], 0.68~0.99), melanin (95% CI, 0.63~0.89), and melanocyte-stained areas (95% CI, 0.70~0.92) were associated with a lower possibility of BCC tumor infiltration over the middle and lower layers. CONCLUSION: We found an inverse correlation between the pigmentation and aggressiveness of BCCs. Clinicians can predict the subclinical infiltration depth of BCC on the basis of the pigmentation observed on dermoscopy. Pigmentation can be considered a favorable prognostic factor for BCC.

Development of Human Rhinovirus RNA Reference Material Using Digital PCR.

The human rhinovirus (RV) is a positive-stranded RNA virus that causes respiratory tract diseases affecting both the upper and lower halves of the respiratory system. RV enhances its replication by concentrating RNA synthesis within a modified host membrane in an intracellular compartment. RV infections often occur alongside infections caused by other respiratory viruses, and the RV virus may remain asymptomatic for extended periods. Alongside qualitative detection, it is essential to accurately quantify RV RNA from clinical samples to explore the relationships between RV viral load, infections caused by the virus, and the resulting symptoms observed in patients. A reference material (RM) is required for quality evaluation, the performance evaluation of molecular diagnostic products, and evaluation of antiviral agents in the laboratory. The preparation process for the RM involves creating an RV RNA mixture by combining RV viral RNA with RNA storage solution and matrix. The resulting RV RNA mixture is scaled up to a volume of 25 mL, then dispensed at 100 µL per vial and stored at -80 °C. The process of measuring the stability and homogeneity of RV RMs was conducted by employing reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Digital PCR is useful for the analysis of standards and can help to improve measurement compatibility: it represents the equivalence of a series of outcomes for reference materials and samples being analyzed when a few measurement procedures are employed, enabling objective comparisons between quantitative findings obtained through various experiments. The number of copies value represents a measured result of approximately 1.6 × 105 copies/µL. The RM has about an 11% bottle-to-bottle homogeneity and shows stable results for 1 week at temperatures of 4 °C and -20 °C and for 12 months at a temperature of -80 °C. The developed RM can enhance the dependability of RV molecular tests by providing a precise reference value for the absolute copy number of a viral target gene. Additionally, it can serve as a reference for diverse studies.

Efficacy of skin rejuvenation with a fractional 1927-nm thulium laser alone or combined with a chemical peel: a controlled histopathological preliminary study in a mouse model.

Many patients demand minimally invasive treatments for skin rejuvenation, such as nonablative laser and superficial chemical peels. Combination therapy yet has not been studied histopathologically. The purpose of this study is to assess the histopathological efficacy of a 1927-nm thulium laser-assisted salicylic acid (SA) peel in skin rejuvenation. A six-segment table was drawn on the shaved back of C57BL/6 mouse. All segments were irradiated with the thulium laser-different tips and passes were used for specific segments. A 30% SA peel was then applied to the right-hand segments. After treatment, the skin samples were collected from each segment and examined for dermal thickness, collagen density, and melanin content. Greater thickness was seen in the combination therapy group compared with the laser alone group and in those segments receiving more passes with larger beam-sized tip. Collagen density increased in all treated skin segments, irrespective of the group. No adverse events were noted in the treated areas. The sample size was small and mouse skin has histological differences with human skin. The combination of a thulium laser and 30% SA peel has a synergistic effect on dermal thickness, so that can be suggested as a novel skin rejuvenation technique.

Comparative Computational Analysis of Spike Protein Structural Stability in SARS-CoV-2 Omicron Subvariants.

The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike (S) protein mutations pose serious threats to current coronavirus disease 2019 (COVID-19) therapies. A comprehensive understanding of the structural stability of SARS-CoV-2 variants is vital for the development of effective therapeutic strategies as it can offer valuable insights into their potential impact on viral infectivity. S protein mediates a virus' attachment to host cells by binding to angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD), and mutations in this protein can affect its stability and binding affinity. We analyzed S protein structural stability in various Omicron subvariants computationally. Notably, the S protein sequences analyzed in this work were obtained directly from our own sample collection. We evaluated the binding free energy between S protein and ACE2 in several complex forms. Additionally, we measured distances between the RBD of each chain in S protein to analyze conformational changes. Unlike most of the prior studies, we analyzed full-length S protein-ACE2 complexes instead of only RBD-ACE2 complexes. Omicron subvariants including BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.2.75_K147E, BA.4.6 and BA.4.6_N658S showed enhanced stability compared to wild type, potentially due to distinct S protein mutations. Among them, BA.2.75 and BA.4.6_N658S exhibited the highest and lowest level of stability, respectively.

A Pilot Split-Neck Case Study to Compare the Efficacy of the Long-Pulsed 755 nm Laser and the 532 nm Picosecond Laser for Acrochordon Removal.

Cutaneous papillomas or acrochorda usually appear after the 4th decade of life in areas with skin folds. Conventional methods of removal are associated with bleeding problems, pain and prolonged sequelae. Thus, acrochorda removal with lasers has gained attention. In this study, we compared the efficacy of two popular laser types with different wavelengths and pulse widths for removal of skin tags. A 60-year-old Korean male noticed skin tags on his neck bilaterally. All tags were treated in a single session, on one side with a picosecond (ps)-domain 532 nm Nd:YAG laser and on the contralateral side with a long-pulsed (LP) 755 nm alexandrite laser. The endpoint for the ps-532 laser was immediate whitening, while that for the LP and quasi-LP (QLP) 755 lasers were visible changes on the surface of the lesion. Antibiotic ointment was applied, dressing was done and clinical photographs were taken. Both lasers effectively removed the skin tags at all settings in a single session without bleeding and with minimal discomfort. Crust formation occurred on both sides with natural shedding within 1 to 2 weeks. Transient erythema lasted longer in the tags treated with the ps-532 laser. At the 5th month of follow-up, residual lesions were detected on the field treated with the ps-532 laser. No persistent side effects such as scarring or postinflammatory hyperpigmentation (PIH) were observed. In conclusion, both the ps-532 nm Nd:YAG and the 755 nm alexandrite lasers ensured safe and effective removal of skin tags in a single session without adverse sequelae.

Periorbital Skin Rejuvenation of Asian Skin Using Microneedle Fractional Radiofrequency.

BACKGROUND: The periorbital area plays an important role cosmetically. Periorbital wrinkles are attributed to long-term, repeated use of orbicularis oris muscles and UV-induced dermal collagen degeneration. Fractional microneedle radiofrequency (RF) treats scars and laxity by creating vertical channels of injury in the dermis, triggering a scarless healing cascade and neocollagenesis. OBJECTIVE: To evaluate the effect and safety of a novel fractional microneedle RF device on periorbital wrinkles based on several objective indicators. METHODS: Eleven healthy Korean patients aged 30 to 75 years with periorbital wrinkles were included in this study. Wrinkle grades were evaluated using the Fitzpatrick wrinkle assessment scale (WAS). The melanin and erythema index, transepidermal water loss (TEWL), and three parameters for elasticity were recorded. Skin biopsies were obtained in patients who consented. RESULTS: All patients exhibited wrinkle improvement in the lateral periorbital area, and two patients also showed efficacy in the lower eyelid area. There was a statistically significant decrease in WAS and a significant improvement in the melanin index of V4 and V5. TEWL also showed a considerable decline on V4 and V5, suggesting that the water content of the skin increased with repeated laser sessions. A peak increase in viscoelasticity and a decrease in retraction time following the first laser application were observed. In the histopathologic examination, the dermis had a denser collagen and elastin content. CONCLUSION: Microneedle fractional RF resulted in statistically significant long-term clinical improvement of periorbital wrinkles and enhanced pigmentation and skin hydration.

The PFC-LH-VTA pathway contributes to social deficits in IRSp53-mutant mice.

Dopamine (DA) neurons in the ventral tegmental area (VTA) promote social brain functions by releasing DA onto nucleus accumbens neurons, but it remains unclear how VTA neurons communicate with cortical neurons. Here, we report that the medial prefrontal cortex (mPFC)-lateral hypothalamus (LH)-VTA pathway contributes to social deficits in mice with IRSp53 deletion restricted to cortical excitatory neurons (Emx1-Cre;Irsp53fl/fl mice). LH-projecting mutant mPFC neurons display abnormally increased excitability involving decreased potassium channel gene expression, leading to excessive excitatory synaptic input to LH-GABA neurons. A circuit-specific IRSp53 deletion in LH-projecting mPFC neurons also increases neuronal excitability and induces social deficits. LH-GABA neurons with excessive mPFC excitatory synaptic input show a compensatory decrease in excitability, weakening the inhibitory LHGABA-VTAGABA pathway and subsequently over-activating VTA-GABA neurons and over-inhibiting VTA-DA neurons. Accordingly, optogenetic activation of the LHGABA-VTAGABA pathway improves social deficits in Emx1-Cre;Irsp53fl/fl mice. Therefore, the mPFC-LHGABA-VTAGABA-VTADA pathway contributes to the social deficits in Emx1-Cre;Irsp53fl/fl mice.

Genomic epidemiology of SARS-CoV-2 variants in South Korea between January 2020 and February 2023.

The Korea Disease Control and Prevention Agency (KDCA) has been conducting national genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). To monitor and characterize circulating SARS-CoV-2 variants in South Korea, 102,873 oropharyngeal/nasopharyngeal swab samples collected from patients with confirmed COVID-19 were sequenced, assigned lineages, and phylogenetically analyzed. Each wave followed a pattern of variants emerging first abroad and then spreading domestically. In 2020, B.41 lineage led the first wave, and B.1.497 dominated the second and third waves. In 2021, the fourth wave was driven by Delta (AY.69 and AY.122.5). In 2022, the fifth to seventh waves were dominated by Omicron sub-lineages BA.1/BA.1.1 and BA.2/BA.2.3, BA.5/BA.5.2, and BN.1, sequentially. The KDCA detected and monitored increasing variants in advance prior to large-scale epidemics, but the repeated emergence of new variants could threaten public health again. Therefore, it is important to continue to monitor and characterize emerging and circulating variants through national genomic surveillance.

Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC→DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ-1 in the adult ACC→DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC→DMS neurons rescues or phenocopies the behaviors of the α2δ-1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.

Increased viral load in patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in the Republic of Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owing to the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2. Its Delta and Omicron variants are more transmissible and pathogenic than other variants. Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. METHODS: The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared using epidemiological data collected at the time of diagnosis. RESULTS: The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. CONCLUSION: Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load.

Results of contact tracing for SARS-CoV-2 Omicron sub-lineages (BA.4, BA.5, BA.2.75) and the household secondary attack risk.

BACKGROUND: This study aimed to assess the contact tracing outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sub-lineages BA.4, BA.5, and BA.2.75 within Republic of Korea, and to generate foundational data for responding to future novel variants. METHODS: We conducted investigations and contact tracing for 79 confirmed BA.4 cases, 396 confirmed BA.5 cases, and 152 confirmed BA.2.75 cases. These cases were identified through random sampling of both domestically confirmed and imported cases, with the goal of evaluating the pattern of occurrence and transmissibility. RESULTS: We detected 79 instances of Omicron sub-lineage BA.4 across a span of 46 days, 396 instances of Omicron sub-lineage BA.5 in 46 days, and 152 instances of Omicron sub-lineage BA.2.75 over 62 days. One patient with severe illness was confirmed among the BA.5 cases; however, there were no reports of severe illness in the confirmed BA.4 and BA.2.75 cases. The secondary attack risk among household contacts were 19.6% for BA.4, 27.8% for BA.5, and 24.3% for BA.2.75. No statistically significant difference was found between the Omicron sub-lineages. CONCLUSION: BA.2.75 did not demonstrate a higher tendency for transmissibility, disease severity, or secondary attack risk within households when compared to BA.4 and BA.5. We will continue to monitor major SARS-CoV-2 variants, and we plan to enhance the disease control and response systems.

Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer.

Immune-related adverse events (irAEs) induced by checkpoint inhibitors involve a multitude of different risk factors. Here, to interrogate the multifaceted underlying mechanisms, we compiled germline exomes and blood transcriptomes with clinical data, before and after checkpoint inhibitor treatment, from 672 patients with cancer. Overall, irAE samples showed a substantially lower contribution of neutrophils in terms of baseline and on-therapy cell counts and gene expression markers related to neutrophil function. Allelic variation of HLA-B correlated with overall irAE risk. Analysis of germline coding variants identified a nonsense mutation in an immunoglobulin superfamily protein, TMEM162. In our cohort and the Cancer Genome Atlas (TCGA) data, TMEM162 alteration was associated with higher peripheral and tumor-infiltrating B cell counts and suppression of regulatory T cells in response to therapy. We developed machine learning models for irAE prediction, validated using additional data from 169 patients. Our results provide valuable insights into risk factors of irAE and their clinical utility.