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.

Seroprevalence of SARS-CoV-2 antibodies among Japanese healthcare workers from 2020 to 2022 as assayed by two commercial kits.

Antibody tests are used as surveillance tools for informing health policy making. However, results may vary by type of antibody assay and timing of sample collection following infection. Long-term longitudinal cohort studies on antibody assay seropositivity have remained limited, especially among Asian populations. Using blood samples obtained at health physicals (2020-2022) of healthcare workers (mass vaccinated with mRNA COVID-19 vaccines) at a Japanese medical center, we measured N-specific antibodies using two commercially available systems. Roche Elecsys Anti-SARS-CoV-2 measures total antibodies and Abbott Alinity SARS-CoV-2 IgG measures only IgG. Among 2538 participants, seroprevalence was found to be 16.6% via total antibody assay versus 12.9% by IgG-only (including grayzone) by mid-June 2022. For 219 cases with a previous PCR-confirmed infection, positivity was 97.3% using total antibody assay versus 76.3% using IgG-only assay at the 2022 health physical. Using PCR positive test date as day 0, while the positivity of the total antibody assay was retained for the entire study period (until more than 24-months post-infection), the IgG-only assay's positivity declined after month 4. The Mantel-Haenszel test found a significant difference in the two assays' seropositivity, between stratified groups of "within 3 months" and "4 months or more" from infection (P < 0.001). Our study found significant differences in seropositivity over time of total antibody versus IgG-only assays, suggesting an optimal assay for retaining sensitivity over the entire infection period when designing seroprevalence studies.

Effect of transcranial static magnetic stimulation over unilateral or bilateral motor association cortex on performance of simple and choice reaction time tasks.

Background: Transcranial static magnetic stimulation (tSMS) is a non-invasive brain stimulation technique that place a strong neodymium magnet on scalp to reduce cortical excitability. We have recently developed a new tSMS device with three magnets placed close to each other (triple tSMS) and confirmed that this new device can produce a stronger and broader static magnetic field than the conventional single tSMS. The aim of the present study was to investigate the effect of the conventional single tSMS as well as triple tSMS over the unilateral or bilateral motor association cortex (MAC) on simple and choice reaction time (SRT and CRT) task performance. Methods: There were two experiments: one involved the conventional tSMS, and the other involved the triple tSMS. In both experiments, right-handed healthy participants received each of the following stimulations for 20 min on different days: tSMS over the unilateral (left) MAC, tSMS over the bilateral MAC, and sham stimulation. The center of the stimulation device was set at the premotor cortex. The participants performed SRT and CRT tasks before, immediately after, and 15 min after the stimulation (Pre, Post 0, and Post 15). We evaluated RT, standard deviation (SD) of RT, and accuracy (error rate). Simulation was also performed to determine the spatial distribution of magnetic field induced by tSMS over the bilateral MAC. Results: The spatial distribution of induced magnetic field was centered around the PMd for both tSMS systems, and the magnetic field reached multiple regions of the MAC as well as the sensorimotor cortices for triple tSMS. SD of CRT was significantly larger at Post 0 as compared to Pre when triple tSMS was applied to the bilateral MAC. No significant findings were noted for the other conditions or variables. Discussion: We found that single tSMS over the unilateral or bilateral MAC did not affect performance of RT tasks, whereas triple tSMS over the bilateral MAC but not over the unilateral MAC increased variability of CRT. Our finding suggests that RT task performance can be modulated using triple tSMS.

Reaction time and brain oscillations in Go/No-go tasks with different meanings of stimulus color.

Color has meaning in particular contexts, and the meaning of color can impact behavioral performance. For example, the meaning of color about traffic rules (blue/green and red mean "go" and "stop" respectively) influences reaction times (RTs) to signals. Specifically, in a Go/No-go task, RTs have been reported to be longer when responding to a red signal and withholding the response to a blue signal (Red Go/Blue No-go task) than when responding to a blue signal and withholding the response to a red signal (Blue Go/Red No-go task). However, the neurophysiological background of this phenomenon has not been fully understood. The purpose of this study was to investigate the brain oscillatory activity associated with the effect of meaning of color on RTs in the Go/No-go task. Twenty participants performed a Blue simple reaction task, a Red simple reaction task, a Blue Go/Red No-go task, and a Red Go/Blue No-go task. We recorded responses to signals and electroencephalogram (EEG) during the tasks and evaluated RTs and changes in spectral power over time, referred to as event-related synchronization (ERS) and event-related desynchronization (ERD). The behavioral results were similar to previous studies. The EEG results showed that frontal beta ERD and theta ERS were greater when signals were presented in blue than red color in both simple reaction and Go/No-go tasks. In addition, the onset of theta ERS was delayed in the Red Go than Blue Go trial in the Go/No-go task. The enhanced beta ERD may indicate that blue signals facilitate motor response, and the delayed onset of theta ERS may indicate the delayed onset of cognitive process when responding to red signals as compared to blue signals in the Go/No-go task. Thus, this delay in cognitive process can be involved in the slow response in the Red Go/Blue No-go task.

Higher synchronization stability with piano experience: relationship with finger and presentation modality.

BACKGROUND: Synchronous finger tapping to external sensory stimuli is more stable for audiovisual combined stimuli than sole auditory or visual stimuli. In addition, piano players are superior in synchronous tapping and manipulating the ring and little fingers as compared to inexperienced individuals. However, it is currently unknown whether the ability to synchronize to external sensory stimuli with the ring finger is at the level of the index finger in piano players. The aim of this study was to compare the effect of piano experience on synchronization stability between the index and ring fingers using auditory, visual, and audiovisual combined stimuli. METHODS: Thirteen piano players and thirteen novices participated in this study. They were instructed to tap with their index or ring finger synchronously to auditory, visual, and audiovisual combined stimuli. The stimuli were presented from an electronic metronome at 1 Hz, and the tapping was performed 30 times in each condition. We analyzed standard deviation of intervals between the stimulus onset and the tap onset as synchronization stability. RESULTS: Synchronization stability for visual stimuli was lower during ring than index finger tapping in novices; however, this decline was absent in piano players. Also, piano players showed the higher synchronization stability for audiovisual combined stimuli than sole visual and auditory stimuli when tapping with the index finger. On the other hand, in novices, synchronization stability was higher for audiovisual combined stimuli than only visual stimuli. CONCLUSIONS: These findings suggest that improvements of both sensorimotor processing and finger motor control by piano practice would contribute to superior synchronization stability.

Differential Effects of Transcranial Static Magnetic Stimulation Over Left and Right Dorsolateral Prefrontal Cortex on Brain Oscillatory Responses During a Working Memory Task.

Transcranial static magnetic stimulation (tSMS) is known to influence behavioral and neural activities. However, although the left and right dorsolateral prefrontal cortex (DLPFC) are associated with different cognitive functions, there remains a lack of knowledge on a difference in the effects of tSMS on cognitive performance and related brain activity between left and right DLPFC stimulations. To address this knowledge gap, we examined how differently tSMS over the left and right DLPFC altered working memory performance and electroencephalographic oscillatory responses using a 2-back task, in which subjects monitor a sequence of stimuli and decide whether a presented stimulus matches the stimulus presented two trials previously. Fourteen healthy adults (five females) performed the 2-back task before, during (20 min after the start of stimulation), immediately after, and 15 min after three different stimulation conditions: tSMS over the left DLPFC, tSMS over the right DLPFC, and sham stimulation. Our preliminary results revealed that while tSMS over the left and right DLPFC impaired working memory performance to a similar extent, the impacts of tSMS on brain oscillatory responses were different between the left and right DLPFC stimulations. Specifically, tSMS over the left DLPFC increased the event-related synchronization in beta band whereas tSMS over the right DLPFC did not show such an effect. These findings support evidence that the left and right DLPFC play different roles in working memory and suggest that the neural mechanism underlying the impairment of working memory by tSMS can be different between left and right DLPFC stimulations.

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.

Cutaneous information processing differs with load type during isometric finger abduction.

During submaximal isometric contraction, there are two different load types: maintenance of a constant limb angle while supporting an inertial load (position task) and maintenance of a constant force by pushing against a rigid restraint (force task). Previous studies demonstrated that performing the position task requires more proprioceptive information. The purpose of this study was to investigate whether there would be a difference in cutaneous information processing between the position and force tasks by assessing the gating effect, which is reduction of amplitude of somatosensory evoked potentials (SEPs), and cutaneomuscular reflex (CMR). Eighteen healthy adults participated in this study. They contracted their right first dorsal interosseous muscle by abducting their index finger to produce a constant force against a rigid restraint that was 20% maximum voluntary contraction (force task), or to maintain a target position corresponding to 10° abduction of the metacarpophalangeal joint while supporting a load equivalent to 20% maximum voluntary contraction (position task). During each task, electrical stimulation was applied to the digital nerves of the right index finger, and SEPs and CMR were recorded from C3' of the International 10-20 system and the right first dorsal interosseous muscle, respectively. Reduction of the amplitude of N33 component of SEPs was significantly larger during the force than position task. In addition, the E2 amplitude of CMR was significantly greater for the force than position task. These findings suggest that cutaneous information processing differs with load type during static muscle contraction.

The effect of prior knowledge of color on reaction time depends on visual modality.

Prior knowledge of color, such as traffic rules (blue/green and red mean "go" and "stop" respectively), can influence reaction times (RTs). Specifically, in a Go/No-go task, where signals were presented by a light-emitting diode (LED) lighting device, RT has been reported to be longer when responding to a red signal and withholding the response to a blue signal (Red Go/Blue No-go task) than when responding to a blue signal and withholding the response to a red signal (Blue Go/Red No-go task). In recent years, a driving simulator has been shown to be effective in evaluation and training of driving skills of dementia and stroke patients. However, it is unknown whether the change in RT observed with the LED lighting device can be replicated with a monitor presenting signals that are different from the real traffic lights in terms of depth and texture. The purpose of this study was to elucidate whether a difference in visual modality (LED and monitor) influences the effect of prior knowledge of color on RTs. Fifteen participants performed a simple reaction task (Blue and Red signals), a Blue Go/Red No-go task, and a Red Go/Blue No-go task. Signals were presented from an LED lighting device (Light condition) and a liquid crystal display (LCD) monitor (Monitor condition). The results showed that there was no significant difference in simple RT by signal color in both conditions. In the Go/No-go task, there was a significant interaction between the type of signal presentation device and the color of signal. Although the RT was significantly longer in the Red Go/Blue No-go than Blue Go/Red No-go task in the Light condition, there was no significant difference in RT between the Blue Go/Red No-go and Red Go/Blue No-go tasks in the Monitor condition. It is interpreted that blue and red signals presented from the LCD monitor were insufficient to evoke a perception of traffic lights as compared to the LED. This study suggests that a difference in the presentation modality (LED and monitor) of visual information can influence the level of object perception and consequently the effect of prior knowledge on behavioral responses.

Antibody response and seroprevalence in healthcare workers after the BNT162b2 vaccination in a University Hospital at Tokyo.

In 2020, we reported a low seroprevalence of N-specific antibodies in 4147 health care workers (HCWs) at a frontline hospital in Tokyo, Japan. In Japan, a vaccine campaign was launched in early 2021. We re-evaluated seroprevalences of N- and S-specific antibodies in 2202 HCWs who took two doses of the BNT162b2 vaccine. In 2021, N-specific seroprevalence remains as low as 1.59%. The seroprevalences were comparable among all HCWs regardless of exposure levels. Almost all of the HCWs elicited S-specific antibodies after vaccination. However, the HCWs who had COVID-19 elicited higher S-specific antibody titers than those who did not have COVID-19. In the HCWs without a history of COVID-19, 1.1% (23 out of 2185) were seropositive with N-specific antibodies, indicating the existence of asymptomatic infections. Also, S-specific antibody titers were higher in females and younger HCWs, and in those who had severe side effects. However, S-specific antibody titers were lower depending on the number of days after the second dose of vaccination specifically in elderly individuals. In conclusion, this study indicates N-specific seroprevalence remains low in HCWs at a frontline hospital in Tokyo. The mRNA vaccine elicited S-specific antibody in HCWs, however, the titers decreased as the days proceeded.

Increased delta variant SARS-CoV-2 infections in a highly vaccinated medical center in Japan.

The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%. With strict infection control protocols including universal masking, only a small number of cases among vaccinated and unvaccinated HCWs were identified before June. As Delta spread in Tokyo, 16 cases among 3,289 fully vaccinated HCWs and 11 cases among 574 unvaccinated HCWs were reported in July and August (case rate in August: 4.0 vs. 19.2 per 1,000). All breakthrough cases were confirmed as Delta. While our study confirms a robust vaccine effectiveness of BNT162b2 vaccine against Delta, rising breakthrough cases suggest that continued infection control measures are warranted in higher risk environments, even when high rates of vaccination coverage are achieved.

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan.

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00-34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53-20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21-9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43-8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80-6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region.

Elevated depressive symptoms among newer and younger healthcare workers in Japan during the COVID-19 pandemic.

AIM: Depression is a frequent outcome of long-term stress, but no studies have examined depression rates among Japanese healthcare workers fighting the COVID-19 pandemic. Therefore, we conducted a web-based interview of hospital employees to assess depression prevalence and factors. METHODS: This observational cohort study was conducted from July to August, 2020, as part of a mandatory health checkup of Juntendo University Hospital employees (Tokyo, Japan). A total of 4239 participants completed a web-based questionnaire on medical history and current health status. The Center for Epidemiologic Studies Depression Scale (CES-D) was used for self-assessment, with a score of ≥16 considered to indicate depression. RESULTS: Among all employees, the proportion of depression was 31.3% in 2020, the highest measured in the last 10 years and substantially greater than the pre-pandemic value in 2019 (27.5%). The proportion of depression for 2020 was significantly higher in new recruits than in employees with more than 2 years of experience (47.0% vs 29.9%, respectively, P < .0001) and in new recruits in 2019 (26.4%, P < .0001). When subdivided by occupation, nurses demonstrated the highest depression rate (43.2%), followed by paramedics (35.1%) and clerks (31.6%), whereas residents (22.9%), doctors (20.4%), teaching staff (18.0%), and part-time staff (15.3%) reported lower depression rates. The positive CES-D score significantly correlated with age (P < .0001). CONCLUSIONS: Younger and newer employees demonstrated the highest rates of depression independent of occupation. Therefore, mental healthcare programs focusing on these vulnerable groups need to be established.

SARS-CoV-2 seroprevalence in healthcare workers at a frontline hospital in Tokyo.

Healthcare workers (HCWs) are highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The actual coronavirus disease (COVID-19) situation, especially in regions that are less affected, has not yet been determined. This study aimed to assess the seroprevalence of SARS-CoV-2 in HCWs working in a frontline hospital in Tokyo, Japan. In this cross-sectional observational study, screening was performed on consented HCWs, including medical, nursing, and other workers, as part of a mandatory health checkup. The screening test results and clinical characteristics of the participants were recorded. The antibody seroprevalence rate among the 4147 participants screened between July 6 and August 21, 2020, was 0.34% (14/4147). There was no significant difference in the seroprevalence rate between frontline HCWs with a high exposure risk and HCWs working in other settings with a low exposure risk. Of those seropositive for SARS-CoV-2, 64% (9/14) were not aware of any symptoms and had not previously been diagnosed with COVID-19. In conclusion, this study provides insights into the extent of infection and immune status in HCWs in Japan, which has a relatively low prevalence of COVID-19. Our findings aid in formulating public health policies to control virus spread in regions with low-intensity COVID-19.