Preoperative collateralization depending on posterior components in the prediction of transient neurological events in moyamoya disease.

Changes in local cerebral blood flow (CBF) are a major cause of transient neurological events (TNEs) after revascularization for moyamoya disease (MMD); however, the influence of preoperative collateral pathway development on TNEs has not yet been investigated. This study included 28 hemispheres from 28 consecutive patients with MMD who underwent surgical revascularization, including a superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, between January 2014 and March 2022. The collateralization pathways included the anterior communicating artery (AcomA) collaterals, posterior communicating artery (PcomA) collaterals, transdural collaterals, posterior pericallosal anastomosis, lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. These collateral pathways were analyzed to identify predictive factors significantly associated with TNEs. TNEs were observed in 11 (39.3%) hemispheres. The development of posterior pericallosal anastomosis and choroidal anastomosis was a significant independent predictor of the occurrence of TNEs after bypass surgery for MMD (P = 0.01, OR 26.9, 95% CI 1.50-480.0; P = 0.002, OR 47.6, 95% CI 2.65-856.6). The development of choroidal and posterior pericallosal anastomosis could be reliable preoperative predictors of TNEs after bypass surgery for MMD. Our results provide useful information for future studies aimed at clarifying the mechanisms underlying TNEs.

Corrigendum: SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge.

[This corrects the article DOI: 10.3389/fmicb.2023.944369.].

Solid brain metastasis mimicking intracerebral hematoma on imaging.

A 79-year-old woman with a history of resection of the ascending colon cancer presented with conscious disturbance, dysarthria, nausea, and dizziness. Computed tomography (CT) revealed striking high-density lesions in the left cerebellum and left frontal lobe with slight perifocal edema. These lesions were suspected the coexistence of spontaneous cerebellar hemorrhage and frontal lobe metastasis, or multiple brain metastases with massive hematoma. Because of the mass effect of the cerebellar lesion and impaired consciousness, she underwent emergency resection of the cerebellar lesion which was found to be composed of grayish abnormal soft solid tissue and did not include an obvious hematoma mass. The pathological findings were consistent with brain metastasis from colon cancer. This is an impressive rare case of intraoperative solid brain metastasis with a clearly homogenous hyper-dense CT appearance mimicking intracerebral hematoma.

Cerebral microbleeds is a predictor of recurrent small vessel cerebrovascular disease: Evaluation based on the recurrent stroke pattern.

OBJECTIVES: An increased number of cerebral microbleeds (CMBs) is considered a predictive factor for recurrent small vessel cerebrovascular diseases, including lacunar infarction and non-lobar intracerebral hemorrhage (ICH). However, it is unclear which recurrent stroke pattern is mainly reflected in the number of CMBs. MATERIALS AND METHODS: This study enrolled 217 patients with their first stroke (148 deep lacunar infarctions and 69 non-lobar ICHs), between January 2009 and March 2015. The numbers of baseline and newly appearing CMBs in patients with recurrent stroke were compared with those in patients with non-recurrent stroke, and the dynamics of the number of CMBs was evaluated according to recurrent stroke patterns. RESULTS: Fifty-nine patients with recurrent stroke were included in this study. A larger number of baseline and newly appearing CMBs was significantly associated with recurrent stroke (p = 0.04, p < 0.001, respectively). Recurrent stroke patterns were divided into four types: deep lacunar infarction/deep lacunar infarction (37 patients), deep lacunar infarction/non-lobar ICH (eight patients), non-lobar ICH/deep lacunar infarction (eight patients), and non-lobar ICH/non-lobar ICH (six patients). The number of newly appearing CMBs was significantly higher in patients with deep lacunar infarction/non-lobar ICH than in those with other recurrent stroke patterns (p = 0.04). CONCLUSIONS: The number of CMBs is associated with recurrent stroke, including deep lacunar infarction and non-lobar ICH, and differs depending on the recurrent stroke patterns. The increase in the number of CMBs was strongly correlated with the deep lacunar infarction/non-lobar ICH recurrence pattern.

Differences and Advantages of Particles versus Liquid Material for Preoperative Intracranial Tumor Embolization: A Retrospective Multicenter Study.

Objectives: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials. Methods: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records. Results: A tortuous access route was the only factor independently associated with complications (p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups (p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor (p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group (p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group (p = 0.006). Conclusion: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case.

Caffeoylquinic Acid Mitigates Neuronal Loss and Cognitive Decline in 5XFAD Mice Without Reducing the Amyloid-ß Plaque Burden.

Background: Caffeoylquinic acid (CQA), which is abundant in coffee beans and Centella asiatica, reportedly improves cognitive function in Alzheimer's disease (AD) model mice, but its effects on neuroinflammation, neuronal loss, and the amyloid-ß (Aß) plaque burden have remained unclear. Objective: To assess the effects of a 16-week treatment with CQA on recognition memory, working memory, Aß levels, neuronal loss, neuroinflammation, and gene expression in the brains of 5XFAD mice, a commonly used mouse model of familial AD. Methods: 5XFAD mice at 7 weeks of age were fed a 0.8% CQA-containing diet for 4 months and then underwent novel object recognition (NOR) and Y-maze tests. The Aß levels and plaque burden were analyzed by enzyme-linked immunosorbent assay and immunofluorescent staining, respectively. Immunostaining of markers of mature neurons, synapses, and glial cells was analyzed. AmpliSeq transcriptome analysis and quantitative reverse-transcription-polymerase chain reaction were performed to assess the effect of CQA on gene expression levels in the cerebral cortex of the 5XFAD mice. Results: CQA treatment for 4 months improved recognition memory and ameliorated the reduction of mature neurons and synaptic function-related gene mRNAs. The Aß levels, plaque burden, and glial markers of neuroinflammation seemed unaffected. Conclusions: These findings suggest that CQA treatment mitigates neuronal loss and improves cognitive function without reducing Aß levels or neuroinflammation. Thus, CQA is a potential therapeutic compound for AD, improving cognitive function via as-yet unknown mechanisms independent of reductions in Aß or neuroinflammation.

SARS-CoV-2 seroprevalence among healthcare workers in a highly vaccinated Japanese medical center from 2020-2023.

Infection-induced SARS-CoV-2 seroprevalence has been studied worldwide. At Juntendo University Hospital (JUH) in Tokyo, Japan, we have consistently conducted serological studies using the blood residue of healthcare workers (HCWs) at annual health examinations since 2020. In this 2023 study (n = 3,594), N-specific seroprevalence (infection-induced) was examined while univariate and multivariate logistic regression analyses were performed to compute ORs of seroprevalence with respect to basic characteristics of participants. We found that the N-specific seroprevalence in 2023 was 54.1%-a jump from 17.7% in 2022, and 1.6% in 2021-with 37.9% as non-PCR-confirmed asymptomatic infection cases. Those younger than 50 (adjusted OR = 1.62; p < .001) and recipients with 4 doses or less of vaccine had a higher risk to be N-positive, ranging from 1.45 times higher for the participants with 4 doses (p < .001) to 4.31 times higher for the participants with 1 dose (p < .001), compared to those with 5 or more doses. Our findings indicate that robust vaccination programs may have helped alleviate symptoms but consequently caused asymptomatic spread in this hospital, especially among younger HCWs. Although having four doses or less was found to be associated with higher risk of infection, the optimal constitution and intervals for effective booster vaccines warrant further investigations.

The impact of serum testosterone level to reflect age-related multi-organ functions.

The aim of this study is to examine the correlation between aging, serum total testosterone and biomarkers of multiple organ functions in men. The participants consisted of 12,547 outpatients, whose serum testosterone level was measured. A multiple regression analysis was conducted to determine whether biomarkers including hemoglobin (Hb), hematocrit (Hct), luteinizing hormone (LH), follicle stimulating hormone (FSH), alkaline phosphatase (ALP), albumin (ALB), creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose (Glu), C-reactive protein (CRP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) values were associated with serum total testosterone concentration. Significant correlations (p < 0.05) were found between total testosterone and Hb, Hct, LH, FSH, ALP, ALB, TG, HDL-C, AST, ALT, Glu, and CRP. In addition, significant correlations (p < 0.05) were found between Hb, Hct, LH, FSH, ALP, ALB, TG and HDL-C associated with [age × testosterone]. This large-scale study provided new insights into correlations between serum testosterone and biomarkers associated with age-related diseases, suggesting that testosterone is especially important for maintaining homeostasis in aging males. Thus, hypogonadism in elderly patients may be associated with multiple organ dysfunctions.

Use of a stent-retriever for treatment of iatrogenic vasospasm secondary to mechanical thrombectomy.

The treatment strategy for iatrogenic intracranial vasospasm has not been established. We reported a rare case of stent-retriever use for the treatment of iatrogenic vasospasm after mechanical thrombectomy. The patient presented acute ischemic stroke due to the occlusion of the left middle cerebral artery (MCA). The patient underwent a successfully mechanical thrombectomy, however, severe stenosis was visualized in MCA, which was considered to be an iatrogenic mechanical vasospasm. This vasospasm was successfully treated with the Solitaire stent device, and the patient recovered from ischemic symptoms. A stent-retriever is a safe and effective treatment for iatrogenic vasospasm after mechanical thrombectomy.

"The microcatheter contrast injection technique": A novel technique to detect the proximal end of a thrombus in mechanical thrombectomy.

Background: An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use "the microcatheter contrast injection (MCI) technique," which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods: In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results: 29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions: The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization.

Transvenous embolization for an intraosseous clival arteriovenous fistula via a proper access route guiding a three-dimensional fusion image: illustrative case.

BACKGROUND: Intraosseous clival arteriovenous fistulas (AVFs), in which the shunt drains extracranially from the posterior and anterior condylar veins rather than from the cavernous sinus (CS), are rare. Targeting embolization of an intraosseous clival AVF is challenging because of its complex venous and skull base anatomy; therefore, a therapeutic strategy based on detailed preoperative radiological findings is required to achieve a favorable outcome. Here, the authors report the successful targeted embolization of an intraosseous clival AVF using an ingenious access route. OBSERVATIONS: A 74-year-old woman presented with left-sided visual impairment, oculomotor nerve palsy, and right facial pain. A fusion image of three-dimensional rotational angiography and cone-beam computed tomography revealed a left CS dural AVF and a right intraosseous clival AVF. The shunt flow of the clival AVF drained extracranially from the posterior and anterior condylar veins via the intraosseous venous route. Transvenous embolization was performed by devising suboccipital, posterior condylar, and intraosseous access routes. The symptoms resolved after the bilateral AVFs were treated. LESSONS: Accurate diagnosis and proper transvenous access based on detailed intraosseous and craniocervical venous information obtained from advanced imaging modalities are key to resolving intraosseous clival AVF.

Complications and outcomes of carotid artery stenting in high-risk cases.

OBJECTIVES: Carotid artery stenting is sometimes adapted for some at-risk cases; however, appropriate treatment timing with stroke onset is controversial. This study aims to identify factors that have an impact on complications and outcomes, especially in patients at high risk. MATERIALS AND METHODS: We examined the characteristics of 152 consecutive patients treated by carotid artery stenting between January 2018 and March 2022 and retrospectively analyzed the risk factors for complications and poor outcomes (modified-Rankin-Scale deterioration), such as patient background, carotid artery stenting risks (access route tortuosity, severe calcification, vulnerable plaque, estimated glomerular filtration rate <30 mL/min/1.73 m2, etc.), characteristics of the stenosis, details of treatment, and treatment timing. RESULTS: The average North American Symptomatic Carotid Endarterectomy Trial criteria score was 68.3% and the lesion length was 20.5±9.7mm. Among patients, 107 (70.4%) had a carotid artery stenting risk. In high-risk carotid artery stenting cases, symptomatic complications occurred in 32 (30.0%), and the 90-day modified Rankin scale score deteriorated in 15 cases (14.0%). Multivariate analysis showed that cases with triple antithrombotic therapy (p=0.003), stenting within 7 days (p=0.0032), and after 28+ days (p=0.0035) of stroke onset were independently associated factors for complications. CONCLUSIONS: This study showed that among risk factors, triple antithrombotic therapy in particular was a risk factor for perioperative complications. Carotid artery stenting for patients with stroke after 28 days of onset affects the prognosis. Therefore, although further study is warranted, waiting more than one month for treatment in patients requiring carotid artery stenting is a potential risk.

Walk-In Hospital Admission of Patients with Subarachnoid Hemorrhage: Clinical Presentation and Outcome.

OBJECTIVE: Neurosurgeons occasionally encounter cases of subarachnoid hemorrhage (SAH) in admitted walk-in patients, termed "walk-in SAH." However, their clinical characteristics have not been fully understood. We thus, aimed to investigate several characteristics of patients with walk-in SAH and compare them with those of patients with good grade SAH who arrived at the hospital by ambulance. METHODS: Between January 2011 and January 2018, consecutive patients with World Federation of Neurosurgical Society (WFNS) grade I and II aneurysmal SAH were enrolled. They were dichotomized into walk-in and ambulance groups, and their demographic and disease-related characteristics were compared. Furthermore, predictors associated with unfavorable outcomes were investigated in patients with walk-in SAH. RESULTS: Of 171 patients with World Federation of Neurosurgical Society grade I and II SAH, 68 (39.8%) were categorized as walk-in SAH. The mean time for diagnosis in patients with walk-in SAH was significantly longer than that in patients who arrived by ambulance (P < 0.01). Multivariate analysis demonstrated that a lower rate of hypertension, high grades on the Barrow Neurological Institute scale, and Early Brain Edema Score were significantly associated with walk-in SAH (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.21-0.91, P = 0.03; OR 0.32, 95% CI 0.13-0.76, P = 0.007; OR 0.11, 95% CI 0.02-0.51, P < 0.0001, respectively). Additionally, severe angiographic vasospasm was a significant predictor of unfavorable outcomes in walk-in SAH (OR 37.7, 95% CI 1.10-1290.90, P = 0.04). CONCLUSIONS: Patients with walk-in SAH exhibit radiological characteristics associated with a more favorable outcome among patients with good grade SAH. Therefore, these patients may have a positive prognosis.

A lithium superionic conductor for millimeter-thick battery electrode.

No design rules have yet been established for producing solid electrolytes with a lithium-ion conductivity high enough to replace liquid electrolytes and expand the performance and battery configuration limits of current lithium ion batteries. Taking advantage of the properties of high-entropy materials, we have designed a highly ion-conductive solid electrolyte by increasing the compositional complexity of a known lithium superionic conductor to eliminate ion migration barriers while maintaining the structural framework for superionic conduction. The synthesized phase with a compositional complexity showed an improved ion conductivity. We showed that the highly conductive solid electrolyte enables charge and discharge of a thick lithium-ion battery cathode at room temperature and thus has potential to change conventional battery configurations.

Increased SARS-CoV-2 seroprevalence and spread of infection without awareness among healthcare workers through 2020-2022 in a Japanese medical center.

Despite Japan's high vaccination coverage, daily numbers of new COVID-19 cases have been high. However, studies on the seroprevalence among Japanese people and the causative factors for rapid spread have remained limited. In this study, we aimed to examine the seroprevalence and associated factors in healthcare workers (HCWs) of a medical center in Tokyo using blood samples drawn at annual check-ups from 2020 to 2022. We found that of the 3,788 HCWs in 2022 (by mid-June), 669 were seropositive for N-specific antibodies (tested by Roche Elecsys Anti-SARS-CoV-2 assay); the seroprevalence surged from 0.3% in 2020 and 1.6% in 2021 to 17.7% in 2022. Notably, our study found 325 (48.6%; 325/669) cases were infected without awareness. Among those with a previously PCR-confirmed SARS-CoV-2 infection during the past three years, 79.0% (282/357) were found after January 2022, after the Omicron variant was first detected in Tokyo at the end of 2021. This study indicates the fast spread of the SARS-CoV-2 among HCWs during the Omicron surge in Japan. The high percentage of infection without awareness may be a key driving factor causing rapid person-to-person transmission, as shown in this medical center with high vaccination coverage and strict infection control measures.

Impact of cisplatin-induced acute kidney injury on long-term renal function in patients with solid tumors.

BACKGROUND: The reality of cisplatin-induced acute kidney injury (CIA) and its effects on long-term renal function remain unclear. The aim of this study was to investigate the incidence and risk factors for CIA development, and if CIA is a useful predictor of long-term renal dysfunction after cisplatin treatment. METHODS: This was a retrospective, single-center, observational, longitudinal follow-up, large cohort study in adult patients with solid tumors treated with cisplatin-based systematic chemotherapy. Electronic medical records were used for all demographic and medical data. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. We assessed long-term renal dysfunction using %ΔeGFR/Y; (the last eGFR value during follow-up)-(the baseline eGFR)/(the baseline eGFR)/year of follow-up × 100. RESULTS: A total of 2191 patients received 8,482 cycles of cisplatin. CIA was observed 359 times (4.2%). Significant risk factors for developing CIA, using multiple linear regression analysis, included: cisplatin administration immediately before the onset of CIA (p < 0.01), liver cancer (p = 0.02), colon cancer (p = 0.04), hypertension (p = 0.03), high estimated glomerular filtration rate (eGFR) (p < 0.01), and high C-reactive protein (CRP) (p = 0.04). Significant risk factors for %ΔeGFR/Y, using multivariate linear regression analysis, included: esophageal cancer (p < 0.01), lung cancer (p < 0.01), pharyngeal cancer (p = 0.02), Head and neck cancer (p < 0.01), liver cancer (p = 0.02), potassium (p < 0.01), and CIA (p < 0.01). CONCLUSIONS: To our knowledge, this is the first study to show that CIA is a significant predictive risk factor for long-term renal dysfunction after cisplatin administration. Effective strategies are needed to prevent CIA in cancer patients.

SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge.

Background: Previous studies have shown that patients with immunosuppression tend to have longer-lasting SARS-CoV-2 infections and a number of mutations were observed during the infection period. However, these studies were, in general, conducted longitudinally. Mutation evolution among groups of patients with immunosuppression have not been well studied, especially among Asian populations. Methods: Our study targeted a nosocomial cluster of SARS-CoV-2 infection in a Japanese medical center during Delta surge (AY.29 sublineage), involving ward nurses and inpatients. Whole-genome sequencing analyses were performed to examine mutation changes. Haplotype and minor variant analyses were furtherly performed to detect the mutations on the viral genomes in detail. In addition, sequences of the first wild-type strain hCoV-19/Wuhan/WIV04/2019 and AY.29 wild-type strain hCoV-19/Japan/TKYK15779/2021 were used as references to assess the phylogenetical development of this cluster. Results: A total of 6 nurses and 14 inpatients were identified as a nosocomial cluster from September 14 through 28, 2021. All were Delta variant (AY.29 sublineage) positive. 92.9% of infected patients (13 out of 14) were either cancer patients and/or receiving immunosuppressive or steroid treatments. Compared to AY.29 wild type, a total of 12 mutations were found in the 20 cases. Haplotype analysis found one index group of eight cases with F274F (N) mutation and 10 other haplotypes with one to three additional mutations. Furthermore, we found that cases with more than three minor variants were all cancer patients under immunosuppressive treatments. The phylogenetical tree analysis, including 20 nosocomial cluster-associated viral genomes, the first wild-type strain and the AY.29 wild-type strain as references, indicated the mutation development of the AY.29 virus in this cluster. Conclusion: Our study of a nosocomial SARS-CoV-2 cluster highlights mutation acquisition during transmission. More importantly, it provided new evidence emphasizing the need to further improve infection control measures to prevent nosocomial infection among immunosuppressed patients.

A multi-centre study of the effects of direct observation of hand hygiene practices on alcohol-based handrub consumption.

Introduction: The World Health Organization recommends monitoring alcohol-based handrub (ABHR) consumption and direct observation of hand hygiene practices to ensure compliance. In Japan monitoring of ABHR consumption is widely performed. However, direct observation is not common, particularly in small facilities and non-acute-care facilities. Hence, the current study aimed to evaluate the longitudinal effects of direct observation of hand hygiene practices and monitoring of ABHR consumption with provision of feedback to healthcare personnel on ABHR consumption and hand hygiene compliance. Methods: We conducted a 4-year prospective intervention study. Monitoring of ABHR consumption and direct observation of hand hygiene practices with monthly feedback to healthcare personnel was implemented in 17 facilities. These consisted of 11 acute-care facilities of varying sizes and six non-acute-care facilities. A generalized linear mixed model analysis was performed to assess factors associated with ABHR consumption. Results: All facilities implemented ABHR consumption monitoring within one month of starting the study. However, the mean time required to implement direct observation of hand hygiene practices was 24.7 (±19.1) months. The ABHR consumption increased significantly (P<0.0001) in all medical facilities after implementing the direct observation. Multivariable regression analysis showed the hospital ward type, duration of ABHR consumption monitoring, and duration of direct observation of hand hygiene practices were independently associated with ABHR consumption. Conclusions: Direct observation of hand hygiene practices with feedback should be implemented more widely in combination with ABHR consumption monitoring to help increase hand hygiene compliance.

Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity.

Many variants of SARS-CoV-2 have emerged around the world. It is therefore important to understand its global viral evolution and the corresponding mutations associated with transmissibility and severity. In this study, we analyzed 112 whole genome sequences of SARS-CoV-2 collected from patients at Juntendo University Hospital in Tokyo and the genome data from entire Japan deposited in Global Initiative on Sharing Avian Influenza Data (GISAID) to examine the relationship of amino acid changes with the transmissibility and the severity of each strain/lineage. We identified 12 lineages, including B.1.1.284, B.1.1.214, R.1, AY.29, and AY.29.1, which were prevalent specifically in Japan. B.1.1.284 was most frequently detected in the second wave, but B.1.1.214 became the predominant lineage in the third wave, indicating that B.1.1.214 has a higher transmissibility than B.1.1.284. The most prevalent lineage during the fourth and fifth wave was B.1.1.7 and AY.29, respectively. In regard to the severity of identified lineages, B.1.1.214 was significantly lower than the reference lineage, B.1.1.284. Analysis of the genome sequence and other traits of each lineage/strain revealed the mutations in S, N, and NSPs that increase the transmissibility and/or severity. These mutations include S: M153T, N: P151L, NSP3: S543P, NSP5: P108S, and NSP12: A423V in B.1.1.284; S: W152L and E484K in R.1; S: H69del, V70del, and N501Y in the Alpha strain; S: L452R, T478K, and P681R in the Delta strain. Furthermore, it is suggested that the transmissibility of B.1.1.214 could be enhanced by the mutations N: M234I, NSP14: P43L, and NSP16: R287I. To address the issue of the virus evolution, it is necessary to continuously monitor the genomes of SARS-CoV-2 and analyze the effects of mutations for developing vaccines and antiviral drugs effective against SARS-CoV-2 variants.

Reactogenicity and immunogenicity of BNT162b2 or mRNA-1273 COVID-19 booster vaccinations after two doses of BNT162b2 among healthcare workers in Japan: a prospective observational study.

BACKGROUND: This study evaluates the immunogenicity and reactogenicity of BNT162b2 and mRNA-1273 booster doses after the primary two-dose BNT162b2 series in Japan and is the first report from Western Pacific region. RESEARCH DESIGN AND METHODS: Healthcare workers receiving the two-dose BNT162b2 series and eligible for booster vaccination were enrolled. Self-reported adverse reactions were recorded for 8 days. Antibody titer was measured at baseline and on day 28. RESULTS: A total of 2,931 and 890 subjects received BNT162b2 (homologous) and mRNA-1273 (heterologous) booster vaccinations, respectively. The anti-SARS-CoV-2 spike protein IgG titer increased by 50.9- and 64.3-fold in the homologous and heterologous groups, respectively. Immunogenicity was greater with increasing age, regardless of sex. Adverse reactions were mild to moderate and decreased with age. The most common adverse reactions were injection-site pain (92.2%), fatigue (71.8%), headache (58.3%), and fever ≥37.5°C (46.5%). Two cases of non-severe myocarditis occurred in the heterologous group and resolved without clinical sequelae. CONCLUSION: Homologous booster schedules had fewer reported adverse reactions; heterologous boosters elicited greater immunogenicity. Among different age groups, subjects aged 60 or over had the lowest immunogenicity before the booster, and both homologous and heterologous boosters restored vaccine immunogenicity level comparable to those of younger age groups.