HLA allele association studies with the kinetics of SARS-CoV-2 spike protein-specific IgG antibody responses to BNT162b2 mRNA vaccine

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer- BioNTech), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ & CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017;OR 2.80, 95% CI 1.05-7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2 while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95% CI 0.05-0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058;OR 0.42, 95% CI 0.15-1.16), B*52:01:01 (p = 0.031;OR 0.38, 95% CI 0.14-1.03), DQA1*03:02:01 (p = 0.028;OR 0.39, 95% CI 0.15-1.00) and DPB1*02:01:02 (p = 0.024;OR 0.45, 95% CI 0.21-0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

Which Is More Effective for Job Satisfaction, Expert Knowledge or Career Status Through Training? Differences between Large Enterprises and SMEs

In this study, we clarified the effect of training by enterprise size for the training service (TOSA Marugoto Business Academy Project [Tosa MBA]) provided by Kochi Prefecture in Japan by applying structural equation modeling to online survey data. In large enterprises, expert knowledge that can be used at work had a positive effect on job satisfaction rather than career status such as annual income and job title. This may have been the case as while promotion involves higher wages and greater privileges, in large enterprises, the extent of responsibility and working hours increase even more. Conversely, in small and medium-sized enterprises (SMEs), career status has a more positive effect on job satisfaction than does expert knowledge. For SMEs with a simple organizational structure, job position has a greater influence on work attitudes. The results present meaningful suggestions to enhance the design of local government training services. © The Author(s) 2022.

Comparison of risk factors for SARS-CoV-2 infection among healthcare workers during Omicron and Delta dominance periods in Japan.

BACKGROUND: The risk factors for coronavirus disease (COVID-19) among healthcare workers (HCWs) might have changed since the emergence of the highly immune evasive Omicron variant. AIM: To compare the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs during the Delta- and Omicron-predominant periods. METHODS: Using data from repeated serosurveys among the staff of a medical research centre in Tokyo, two cohorts were established: Delta period cohort (N = 858) and Omicron period cohort (N = 652). The potential risk factors were assessed using a questionnaire. Acute/current or past SARS-CoV-2 infection was identified by polymerase chain reaction or anti-nucleocapsid antibody tests, respectively. Poisson regression was used to calculate the risk ratio (RR) of infection risk. FINDINGS: The risk of SARS-CoV-2 infection during the early Omicron-predominant period was 3.4-fold higher than during the Delta-predominant period. Neither working in a COVID-19-related department nor having a higher degree of occupational exposure to SARS-CoV-2 was associated with an increased infection risk during both periods. During the Omicron-predominant period, infection risk was higher among those who spent ≥30 min in closed spaces, crowded spaces, and close-contact settings without wearing mask (≥3 times versus never: RR: 6.62; 95% confidence interval: 3.01-14.58), whereas no such association was found during the Delta period. CONCLUSION: Occupational exposure to COVID-19-related work was not associated with the risk of SARS-CoV-2 infection in the Delta or Omicron period, whereas high-risk behaviours were associated with an increased infection risk during the Omicron period.

Which Is More Effective for Job Satisfaction, Expert Knowledge or Career Status Through Training? Differences between Large Enterprises and SMEs

In this study, we clarified the effect of training by enterprise size for the training service (TOSA Marugoto Business Academy Project [Tosa MBA]) provided by Kochi Prefecture in Japan by applying structural equation modeling to online survey data. In large enterprises, expert knowledge that can be used at work had a positive effect on job satisfaction rather than career status such as annual income and job title. This may have been the case as while promotion involves higher wages and greater privileges, in large enterprises, the extent of responsibility and working hours increase even more. Conversely, in small and medium-sized enterprises (SMEs), career status has a more positive effect on job satisfaction than does expert knowledge. For SMEs with a simple organizational structure, job position has a greater influence on work attitudes. The results present meaningful suggestions to enhance the design of local government training services. © The Author(s) 2022.

Development of a System to Support Operators When a Ventilator Alarm Happens

Objective: This paper researches the behavior of ventilator operators from a cognitive perspective. Especially, based on the performance of the operator when an alarm happens, the system is built to support the operator’s decisions. Introduction: Because of Covid-19, more operators were needed who could correctly operate the ventilator. Even inexperienced operators might operate the ventilator. Therefore, training support systems such as simulators that could simulate alarm situations are needed to train operators of the ventilator. An Operations Information Screen (OIS) was created that included logical decisions. The OIS is used to investigate the behavior of the inexperienced operators during ventilator alarms. Methods: The participants are the seven the IG operators in the previous study. The IG operator’s behavior during a ventilator alarm using the OIS is video recorded. The verbal protocol data are also recorded to examine the thinking during the manipulation. After the experiment, the video recordings were reviewed with the participants and interviewed about the reasons for their speeches and behaviors. Results: From the analysis of the behavior and the verbal protocol, it was found to be a logical behavior. And, there was no behavior based on assumptions. An inexperienced operator could use the OIS to experience and learn the decisions of a skilled operator. The OIS could be used for education and training to learn the operating procedures performed by skilled operators in a short period of time. Applications: The results of this study are for alarms with machine side factors. Currently, the operators’ behavior is being analyzed for alarms caused by patient changes, and the OIS is being developed. © 2022, Springer Nature Switzerland AG.

Changes in Physical Activity, Physical Function, and Depressive Symptoms Associated With the Coronavirus Disease 2019 Pandemic in Japanese Patients Undergoing Hemodialysis

Background: There are concerns about the impact of the coronavirus disease 2019 (COVID-19) pandemic on physical and mental health. This study aimed to investigate changes in physical activity, physical function, and depressive symptoms during the COVID-19 pandemic in Japanese hemodialysis patients. Method(s): This retrospective longitudinal study included 159 clinically stable outpatients (mean age, 66.8+/-10.9 years;men, 62.2%;median hemodialysis vintage, 8 years) who underwent maintenance hemodialysis at two Japanese dialysis centers between April 2019 and March 2021. Participants' physical activity (steps taken per non-dialysis day), physical function (walking speed and leg strength), and depressive symptoms (Center for Epidemiologic Studies Depression [CES-D] score) before and during the COVID-19 pandemic were compared. Result(s): The steps on non-dialysis day was significantly lower during than before the COVID-19 pandemic (P < 0.01). On the other hand, there were no significant differences in walking speed, leg strength, and CES-D score before and during the COVID-19 pandemic (Figure). Conclusion(s): Although a decline in physical activity during the COVID-19 pandemic was not prevented, no negative impacts of declining physical activity on physical function and depressive symptoms were observed. This is likely because we have implemented a long-term disease management program, such as regularly assessing the physical function and mental status of the patients. Our findings may provide insight into disease management in hemodialysis patients after the COVID-19 pandemic.

Japan prospective multicenter study for optimization of COVID-19 vaccinations based on the immune response and safety profile in Inflammatory Bowel Disease patients: Interim analyses of the J-COMBAT trial

Background Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Methods IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1–62.3;p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0–472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8–134.1]) than for BNT162b2 (39.6 [35.2–44.6], p= 0.0001). Systemic steroids (22.9 [13.9–37.7], p=0.0119), IM (24.2 [18.7–31.4], p<0.0001), anti-TNF agents (20.8 [15.3–28.3], p<0.0001), vedolizumab (25.2 [15.0–42.2], p=0.0409), ustekinumab (28.9 [18.5–45.0], p=0.0754), and tofacitinib (5.5 [2.8–10.9], p<0.0001), but not oral 5-ASA (39.1 [31.9–47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.

JAPAN PROSPECTIVE MULTICENTER STUDY FOR OPTIMIZATION OF COVID-19 VACCINATIONS BASED ON THE IMMUNE RESPONSE AND SAFETY PROFILE IN INFLAMMATORY BOWEL DISEASE PATIENTS: INTERIM ANALYSES

Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Subjects and Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti- TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID- 19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA- 1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5- ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs. (Table Presented) (Table Presented)

The learning analytics and institutional research based on the usage of Moodle after COVID-19 pandemic

Many universities had to use online based education in 2020 due to COVID-19 pandemic. For asynchronous education, LMS (Learning Management Systems) such as Moodle were used. In this paper, learning analytics and institutional research were done based on the logs of Moodle, focused on during the COVID-19 pandemic. The analytics of four cases were done;(1) the numbers of modules, (2) the monthly learners' access logs (3) the monthly usage per activities, and (4) how many feedbacks were done with assignments modules. Although the usage of Moodle was highly increased from that of before the pandemic, usage of providing resources such as PDFs and videos were main cases. In addition to this, the number of feedbacks differed widely according to the courses. Although the COVID-19 pandemic might cause the increasing of the usage of Moodle, there is a room for improvement in the way of its usage. © 2021 IEEE.

Japan prospective multicenter study for optimization of COVID-19 vaccinations based on the immune response and safety profile in Inflammatory Bowel Disease patients: Interim analyses of the J-COMBAT trial

Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and nonadministrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5-ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.

A case of acute subdural hematoma associated with severe COVID‒19 under extracorporeal membrane oxygenation (ECMO)

Patients with Coronavirus disease 2019 (COVID-19) who receive extracorporeal membrane oxygenation (ECMO) tend to show extreme hypercoagulability and require intensive anticoagulant therapy. The prognosis is extremely poor in patients with intracranial hemorrhage. We report a case of COVID-19 complicated by acute subdural hematoma, which necessitated craniotomy for hematoma evacuation to improve the patient's prognosis. A 60-year-old man diagnosed with COVID-19 presented with severe respiratory failure and hypercoagulability and underwent ECMO along with intensive anticoagulant therapy with a large dose of heparin. Physical examination revealed anisocoria secondary to acute subdural hematoma. He denied a history of head injury, and computed tomography angiography revealed no vascular lesions. We diagnosed the patient with a non-traumatic, simple type hematoma. We discussed this case with the attending physician and reviewed the surgical indications and procedures. The attending physician recommended postoperative heparin withdrawal with ECMO. The hematoma was evacuated using a small crani-otomy. Considering the risk of COVID-19, we cautiously performed all intraoperative procedures, especially those associated with aerosol generation, such as irrigation and the use of the craniotome. Heparin was discontinued postoperatively. The modified Rankin scale (mRS) score on postoperative day 90 was mRS 3. Optimal infection control measures prevented nosocomial infections in this patient despite the emergency surgical intervention.

Remote Learning of Speaking in Syntactic Forms with Robot-Avatar-Assisted Language Learning System

To help second language (L2) learners acquire oral communication skills, dialogue-based computer-assisted language learning (DB-CALL) systems are attracting more interest than ever. When robot-assisted language learning (RALL) is used for realizing such systems, L2 learners are provided with a sense of reality and tension similar to that in a real L2 conversation. At the same time, there are increasing demands for remote learning, accelerated in part by the spread of the novel coronavirus. We have therefore developed a robot-avatar-assisted language learning system that simulates a trialogue in English with two robot avatars and a learner for remote learning. The conversation scenarios deal with various daily topics to keep the learner’s interest and the system prompts the learner to acquire oral skills by using specific syntactic forms in conversation. We conducted a six-day remote learning experiment with ten Japanese university students to evaluate the learning effect, using eye gaze as an index of the learners’ degree of concentration. Our findings demonstrated the effectiveness of our system for remote learning and showed that the learners’ eye gaze activities changed between question answering and repeating tasks. © 2021, Springer Nature Switzerland AG.

A Modeling Research on How to Solve Ventilator Alarms from Behavioral and Cognitive Perspectives

Objective: This paper was studied the behavior of ventilator operators from a cognitive perspective. A model was built from the behavior of the operators, especially when an alarm happened. Introduction: The frequency of ventilator use is increasing due to COVID-19. Thus, there is an increasing need for staff who can manipulate the ventilator appropriately. There is a need for a support system that will enable the operator to manipulate the equipment appropriately for the situation, especially when an alarm happens. Methods: The operator’s behavior during the ventilator alarm was video-recorded. The verbal protocol data were also recorded to examine the thinking during the manipulation. After the experiment, the video recordings were reviewed with the participants and interviewed about the reasons for their speeches and behaviors. Results: As a result of behavioral analysis of each participant, behavioral patterns split into “Skilled Group (SG)” and “Inexperienced Group (IG)” around about 17 s after the alarm happened. From the verbal protocol data and interview data obtained from the experiment, the reasons why the behaviors divided into two groups were analyzed. Based on these results, the cognitive reasons behind the behavior were clarified. In addition, a cognitive model of the operators when a ventilator alarm happens was built. Applications: The results of this research can be applied not only to the manipulation of ventilator alarms, but also to the manipulation of medical equipment, for example, ECMO (Extra Corporeal Membrane Oxygenation). © 2021, Springer Nature Switzerland AG.