90-Day outcomes in patients with severe COVID-19 pneumonia treated with invasive mechanical ventilation.

BACKGROUND: There are few reports detailing the prognostic factors of severe COVID-19 pneumonia requiring invasive ventilation. We investigated the long-term prognosis and evaluated which factors influenced outcomes in these patients. METHODS: Data was reviewed from severe adult COVID-19 cases admitted to our hospital and treated with mechanical ventilation between February 1, 2020, and October 30, 2021. On admission to our hospital, comorbidities and laboratory findings were collected from clinical records. Prognostic information for 90 days after diagnosis was also obtained from hospitals where patients were transferred after their conditions stabilized. RESULTS: Prognostic information was obtained in 133 patients, of which 106 were males (79.7 %). Of the 133 patients, 67 were discharged (51.5 %), 21 continued inpatient care (15.8 %), and 45 died (33.8 %). Age, Charlson Risk Index, and the number of patients on hemodialysis were significantly higher in the deceased group. There were no differences in therapeutic interventions between survivors and those who died except for a higher rate of muscle relaxant and vasopressor usage in the deceased group. Laboratory findings on admission showed significantly higher levels of BUN, creatinine, and serum Krebs von den Lungen 6 (KL-6), and significantly lower platelet counts, hemoglobin, and alanine aminotransferase in those who died. Multivariate analysis revealed that age, hemodialysis, lower platelet counts, and higher KL-6 were independent predictors for 90-day mortality. CONCLUSIONS: Older age, hemodialysis, lower platelet counts and high KL-6 on admission were identified as independent predictors of 90-day mortality in patients with respiratory failure due to severe COVID-19 under invasive mechanical ventilation.

Factors influencing parental COVID-19 vaccination willingness for children in Japan.

Objectives: This study aims to investigate the factors influencing parental willingness in COVID-19 vaccination for children in Japan in light of the introduction of pediatric vaccines. Methods: An online survey was conducted in February 2022, coinciding with the imminent start of pediatric COVID-19 vaccinations in Japan. It assessed attitudes toward vaccine uptake and included questions about health-related attributes, psychological considerations, and sources of COVID-19 information. Data from 2,419 respondents who had children under the age of 12 were analyzed using multinomial logistic regression to identify factors associated with parental willingness towards COVID-19 vaccination for children. The outcomes were "agree" (in favor of vaccination), "not sure" (undecided), with "disagree" (against vaccination) as the reference category. Results: Among participants supportive of vaccination ("agree" compared to the "disagree" reference), salient determinants included: gender (Men in reference to women: odds ratio [OR] 1.54; 95 % confidence interval [CI] 1.11-2.15), highest educational level (Junior College/Vocational in reference to under high school: OR 0.61; 95 % CI 0.40-0.93, Bachelor's /Master's/Doctoral degree in reference to under high school: OR 0.59; 95 % CI 0.42-0.84), perception of benefits of COVID-19 vaccination (Significant in reference to Insignificant: OR 2.04; 95 % CI 1.26-3.28), perception of risks of COVID-19 vaccination (Significant in reference to Insignificant: OR 0.28; 95 % CI 0.19-0.42, Neutral in reference to Insignificant: OR 0.48; 95 % CI 0.33-0.71), the number of referenced information sources utilized for COVID-19 was associated with attitudes towards children's vaccination (OR 1.02; 95 % CI 1.00-1.04). Conclusion: The study highlights the multifaceted factors influencing parents' COVID-19 vaccination attitudes for their children, encompassing socioeconomic, health, psychological, and informational aspects. Factors like cautious information gathering, vaccine concerns and diverse referenced information sources impact willingness. To facilitate informed decision-making, essential measures include government risk communication, widespread vaccine information dissemination, and enhancing parents' health information accessibility and evaluation skills are important.

A higher area under the concentration-time curve/minimum inhibitory concentration target as a potential prognostic factor for vancomycin treatment of methicillin-resistant Staphylococcus aureus meningitis: A case report.

The area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) - guided approach is recommended for vancomycin therapeutic drug monitoring in severe methicillin-resistant Staphylococcus aureus (MRSA) infection. However, evidence regarding the efficacy of vancomycin AUC-guided strategies for the treatment of systemic infections is limited. This case report describes the successful treatment of MRSA meningitis, with vancomycin using a higher AUC/MIC target. A 61-year-old woman who underwent ventriculoperitoneal (VP) shunt placement for subarachnoid hemorrhage, developed MRSA meningitis due to shunt infection. Vancomycin was administered intravenously, with concurrent monitoring of serum and cerebrospinal fluid (CSF) vancomycin concentrations and AUC/MIC. On post-operative day (POD) 24 of VP shunt placement, the vancomycin trough concentration and AUC/MIC were 12.0 µg/mL and 515, respectively, with persistently positive CSF culture. On POD 28, the trough concentration and AUC/MIC were 18.6 µg/mL and 610, respectively. There were no major adverse events, and CSF culture turned negative on POD 30. The vancomycin CSF-to-serum ratio was approximately 41 %. For patients with MRSA meningitis, we suggest an optimal therapeutic range with a vancomycin AUC/MIC target near the upper limit of the therapeutic window.

Trust in governments, public health institutions, and other information sources as determinants of COVID-19 vaccine uptake behavior in Japan.

OBJECTIVES: Trust in governments and public institutions as a determinant of public health outcomes has gained increased attention since the COVID-19 pandemic. Provided historically low confidence in vaccines in Japan, investigating the role of trust in information sources and actual COVID-19 vaccination uptake behavior will be invaluable for future vaccine promotion policymaking. Therefore, the objective of this study was to elucidate the determinants of COVID-19 vaccination uptake and evaluate the relationship between trust in different information sources and COVID-19 vaccination behavior in Japan. METHODS: For this study, we leveraged a longitudinal series of web-based surveys of 19,174 individuals in Japan conducted between 2021 and 2022 which asked questions regarding a wide range of sociodemographic and psychographic characteristics related to the COVID-19 pandemic. Determinant analysis for vaccination (at least one dose of a COVID-19 vaccine) was conducted via multiple logistic regression, and odds ratios (OR) with 95% confidence intervals (CI) were estimated. RESULTS: After adjustment for sociodemographic determinants of vaccine uptake, aggregate trust in the systems and institutions of vaccine approval (OR: 1.42, 95% CI: 1.30-1.56), and trust in information about the COVID-19 pandemic coming from government sources (OR: 1.27, 95% CI: 1.12-1.44) were found to be consistently powerful predictors of COVID-19 vaccination. Trust in media sources including traditional media (OR: 1.21, 95% CI: 1.07-1.36), and the internet (OR: 0.77, 95% CI: 0.66-0.89) had significant and opposing effects. CONCLUSIONS: Our findings support the broader hypothesis that trust in governments and public health institutions remains a powerful determinant for COVID-19 vaccine uptake in Japan. We also found that vaccination decision-making is a multifactorial process that includes the synthesis of trust in public institutions and media, and its interaction with psychosocial determinants such as prosociality and health literacy. We hope to apply this study's findings towards future vaccine programs for contagious diseases.

Findings from a discontinued clinical trial of favipiravir in high-risk patients with early-onset COVID-19.

INTRODUCTION: Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression. METHODS: A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 h of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization. RESULTS: The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 h of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 µg/mL. CONCLUSIONS: Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic.

Inhibitory effects of vaginal Lactobacilli on Candida albicans growth, hyphal formation, biofilm development, and epithelial cell adhesion.

Introduction: Antifungal agents are not always efficient in resolving vulvovaginal candidiasis (VVC), a common genital infection caused by the overgrowth of Candida spp., including Candida albicans, or in preventing recurrent infections. Although lactobacilli (which are dominant microorganisms constituting healthy human vaginal microbiota) are important barriers against VVC, the Lactobacillus metabolite concentration needed to suppress VVC is unknown. Methods: We quantitatively evaluated Lactobacillus metabolite concentrations to determine their effect on Candida spp., including 27 vaginal strains of Lactobacillus crispatus, L. jensenii, L. gasseri, Lacticaseibacillus rhamnosus, and Limosilactobacillus vaginalis, with inhibitory abilities against biofilms of C. albicans clinical isolates. Results: Lactobacillus culture supernatants suppressed viable fungi by approximately 24%-92% relative to preformed C. albicans biofilms; however, their suppression differed among strains and not species. A moderate negative correlation was found between Lactobacillus lactate production and biofilm formation, but no correlation was observed between hydrogen peroxide production and biofilm formation. Both lactate and hydrogen peroxide were required to suppress C. albicans planktonic cell growth. Lactobacillus strains that significantly inhibited biofilm formation in culture supernatant also inhibited C. albicans adhesion to epithelial cells in an actual live bacterial adhesion competition test. Discussion: Healthy human microflora and their metabolites may play important roles in the development of new antifungal agent against C. albicans-induced VVC.

Characteristics of needlestick and sharps injuries of the hands in the operating room among orthopedic surgeons in Japan.

Among the reports on needlestick and sharps injuries (NSIs), many are orthopedic-related due to the frequent use of sharp devices such as pins and wires. This study aimed to identify high-risk instruments, the most common injury sites for each instrument, and the circumstances of NSIs of the hand during orthopedic surgeries in Japan. Incidents of exposure to blood or bodily fluids among physicians during orthopedic surgeries reported to the Japan-EPINet between 2000 and 2015 were included in this study. The four most common devices were identified and the associations among years of experience, equipment users, and injured sites were analyzed. We identified 666 cases of NSIs affecting orthopedic surgeons in the operating room. The instrument most frequently responsible for NSIs was suture needles, which were involved in 265 cases (39.7%). The second most common instrument was pins/wires, which was involved in 111 cases (16.6%). NSIs of the hands of orthopedic surgeons were frequently caused by suture needles used in all surgeries, but relatively often caused by orthopedic devices. Orthopedic surgeons must be aware that they are at risk of NSIs and must take appropriate measures and always be cautious when performing surgery, regardless of their years of experience.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

First nationwide survey of infection prevention and control among healthcare facilities in Japan: impact of the national regulatory system.

BACKGROUND: Infection prevention and control (IPC) measures in Japan are facilitated by a financial incentive process at the national level, where facilities are categorized into three groups (Tier 1, Tier 2, or no financial incentive). However, its impact on IPC at the facility level using a validated tool has not been measured. METHODS: A nationwide cross-sectional study was conducted from August 2019 to January 2020 to evaluate the situation of IPC programs in Japan, using the global IPC Assessment Framework (IPCAF) developed by the World Health Organization. Combined with the information on the national financial incentive system, the demographics of facilities and each IPCAF item were descriptively analyzed. IPCAF scores were analyzed according to the facility level of care and the national financial incentive system for IPC facility status, using Dunn-Bonferroni and Mann-Whitney U tests. RESULTS: Fifty-nine facilities in Japan responded to the IPCAF survey: 34 private facilities (57.6%) and 25 public facilities (42.4%). Of these, 11 (18.6%), 29 (49.2%), and 19 (32.3%) were primary, secondary, and tertiary care facilities, respectively. According to the national financial incentive system for IPC, 45 (76.3%), 11 (18.6%), and three (5.1%) facilities were categorized as Tier 1, Tier 2, and no financial incentive system, respectively. Based on the IPCAF total score, more than half of the facilities were categorized as "Advanced" (n = 31, 55.3%), followed by "Intermediate" (n = 21, 37.5%). The IPCAF total score increased as the facility level of care increased, while no statistically significant difference was identified between the secondary and tertiary care facilities (p = 0.79). There was a significant difference between Tier 1 and Tier 2 for all core components and total scores. Core components 5 (multimodal strategies for implementation of IPC interventions) and 6 (monitoring/audit of IPC and feedback) were characteristically low in Japan with a median score of 65.0 (interquartile range 40.0-85.0) and 67.5 (interquartile range 52.5-87.5), respectively. CONCLUSIONS: The national financial incentive system was associated with IPC programs at facility level in Japan. The current financial incentive system does not emphasize the multimodal strategy or cover monitoring/audit, and an additional systematic approach may be required to further promote IPC for more practical healthcare-associated infection prevention.

Preventive Behaviors and Information Sources during COVID-19 Pandemic: A Cross-Sectional Study in Japan.

BACKGROUND: individual preventive behaviors are one of the key measures needed to prevent the spread of COVID-19. This study sought to identify the factors associated with the adoption of COVID-19 preventive measures, focusing specifically on information sources. METHODS: we conducted a nationally representative cross-sectional survey of 30,053 Japanese adults in February 2021. The survey asked about socioeconomic, health-related, and psychological characteristics, attitudes toward immunization, and the use of information sources regarding COVID-19. We have constructed multivariable logistic regression to estimate the factors associated with the adoption of three preventive measures: 3Cs avoidance, hand hygiene and respiratory hygiene. RESULTS: socioeconomic variables, psychological variables, and the use of information sources are significantly associated with the adoption of preventive measures. The more information sources one uses, the more likely one is to adopt preventive measures. Trust in healthcare professionals is positively associated with adopting preventive measures. On the other hand, negative correlations between trust in social media and preventive behaviors were observed. CONCLUSIONS: encouraging access to multiple information sources, utilizing communication channels, and modifying messaging according to target groups are essential to promote COVID-19 preventive measures.

Predicting the aggravation of coronavirus disease-19 pneumonia using chest computed tomography scans.

Presently, coronavirus disease-19 (COVID-19) is spreading worldwide without an effective treatment method. For COVID-19, which is often asymptomatic, it is essential to adopt a method that does not cause aggravation, as well as a method to prevent infection. Whether aggravation can be predicted by analyzing the extent of lung damage on chest computed tomography (CT) scans was examined. The extent of lung damage on pre-intubation chest CT scans of 277 patients with COVID-19 was assessed. It was observed that aggravation occurred when the CT scan showed extensive damage associated with ground-glass opacification and/or consolidation (p < 0.0001). The extent of lung damage was similar across the upper, middle, and lower fields. Furthermore, upon comparing the extent of lung damage based on the number of days after onset, a significant difference was found between the severe pneumonia group (SPG) with intubation or those who died and non-severe pneumonia group (NSPG) ≥3 days after onset, with aggravation observed when ≥14.5% of the lungs exhibited damage at 3-5 days (sensitivity: 88.2%, specificity: 72.4%) and when ≥20.1% of the lungs exhibited damage at 6-8 days (sensitivity: 88.2%, specificity: 69.4%). Patients with aggravation suddenly developed hypoxemia after 7 days from the onset; however, chest CT scans obtained in the paucisymptomatic phase without hypoxemia indicated that subsequent aggravation could be predicted based on the degree of lung damage. Furthermore, in subjects aged ≥65 years, a significant difference between the SPG and NSPG was observed in the extent of lung damage early beginning from 3 days after onset, and it was found that the degree of lung damage could serve as a predictor of aggravation. Therefore, to predict and improve prognosis through rapid and appropriate management, evaluating patients with factors indicating poor prognosis using chest CT is essential.

SARS-CoV-2 Delta AY.1 Variant Cluster in an Accommodation Facility for COVID-19: Cluster Report.

BACKGROUND: This study aimed to examine the cause of and effective measures against cluster infections, including the delta AY.1 variant of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that occurred in an accommodation facility. METHODS: We surveyed the zoning and ventilation systems of the cluster accommodation, examined the staff's working conditions, conducted an interview, and administered a SARS-CoV-2 test (positive samples were further tested with molecular biological test). RESULTS: Among the 99 employees working at the accommodation, 10 were infected with the delta AY.1 variant. The causes of the cluster infections were close-distance conversations without an unwoven-three-layer mask and contact for approximately five minutes with an unwoven mask under hypoventilated conditions. CONCLUSIONS: The Delta AY.1 infection may occur via aerosols and an unwoven mask might not prevent infection in poorly ventilated small spaces. Routine infection detection and responding quickly and appropriately to positive results helps to prevent clusters from spreading.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria. RESULTS: Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41). CONCLUSION: FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.

Factors associated with reversals of COVID-19 vaccination willingness: Results from two longitudinal, national surveys in Japan 2021-2022.

Background: Research characterizing changes of heart with respect to vaccine intention is scarce, and very little research considers those who were initially vaccine willing but became hesitant. Here, we sought to assess the factors related to reversals of vaccine willingness. Methods: We conducted a longitudinal, national survey on vaccination intention among Japanese adults aged 20 years or older, with the first questionnaire performed in February-March 2021 (N = 30,053) and the follow-up in February 2022 (N = 19,195, response rate 63.9%). The study population comprised those who reported vaccine willingness in the first survey, with the outcome variable being development of vaccine hesitancy at follow-up. We performed a regression analysis of vaccination status using sociodemographic, health-related, psychologic/attitudinal, and information-related variables as predictors. We used the sparse group minimax concave penalty (MCP) to select the optimum group of covariates for the logistic regression. Findings: Of 11,118 (57.9%) respondents who previously expressed interest in vaccination, 10,684 (96.1%) and 434 (3.9%) were in the vaccine willing and hesitant groups, respectively. Several covariates were found to significantly predict vaccine hesitancy, including marital status, influenza vaccine history, COVID-19 infection/testing history, engagement in COVID-19 preventive measures, perceived risks/benefits of the COVID-19 vaccine, and attitudes regarding vaccination policies and norms. The use of certain information sources was also associated with vaccine hesitancy. Interpretation: Sociodemographic, health-related, psychologic/attitudinal, and information-related variables predicted the development of vaccine hesitancy among those with prior willingness. Most of these predictors were also associated with vaccination status. Funding: The present work was supported in part by a grant from the Kanagawa Prefectural Government of Japan and by AIST government subsidies.

Characterising reasons for reversals of COVID-19 vaccination hesitancy among Japanese people: One-year follow-up survey.

Background: Vaccine hesitancy is a global public health threat. We present unique data that characterises those who experienced reversals of COVID-19 vaccination hesitancy in Japan. Methods: We administered a questionnaire on vaccination intention among 30053 Japanese adults aged 20 years or older before the COVID-19 vaccination was available to the general population (first survey) and conducted a follow-up survey on vaccination status one year later in February 2022 (second survey). Those who responded in the first survey that they did not intend to be vaccinated or were unsure and then responded in the second survey that they were vaccinated or intend to be vaccinated were asked about the reasons for their change of heart. Based on previous literature and expert opinion, 31 reasons for changing vaccination intention were compiled and respondents were asked to choose which among them applied to themselves, with multiple responses possible. Based on the results of those responses, each individual was then clustered using the Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction technique and Ordering Points To Identify the Clustering Structure (OPTICS) algorithm. We then identified unique characteristics among each of the sub-populations (clusters). Findings: In the second survey we received 19195 responses (response rate 63.9%), of which 8077 responded 'no' or 'not sure' in the first survey regarding their intention to be vaccinated. Of these, 5861 responded having received or intending to receive the vaccine (72.6%). We detected six and five sub-populations (clusters) among the 'no' group and 'not sure' group, respectively. The clusters were characterized by perceived benefits of vaccination, including the COVID-19 vaccine, awareness of the COVID-19 vaccination status of those close to them, recognition of the social significance of COVID-19 vaccination for the spread of infection, and dispelled concerns about short-term adverse reactions and the safety of the COVID-19 vaccine. Work and personal relationship reasons were also found to be a unique overarching reason for vaccination changes of heart only among those who did not intend to vaccinate. Interpretation: Those who changed their intention to accept COVID-19 vaccination as well as their unique characteristics as detailed in this study will be important entry points when discussing how to promote vaccination to those who are hesitant to vaccinate in the future. Funding: The present work was supported in part by a grant from the Kanagawa Prefectural Government of Japan and by AIST government subsidies.

Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines.

BACKGROUND: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. METHODS: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. RESULTS: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. CONCLUSIONS: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.

A Case of Exacerbation of Haloperidol-Induced Rhabdomyolysis Following the Onset of COVID-19.

BACKGROUND Rhabdomyolysis is a condition in which intracellular components are released into the blood and urine. Rhabdomyolysis can be caused by drug-related complications and COVID-19; however, the underlying mechanism is not clear. In this study, we report a case of rhabdomyolysis complicated by COVID-19, in which we presumed that the cause of rhabdomyolysis was related to prior administration of haloperidol by assessment of the drug history and progression of myopathy. CASE REPORT A 52-year-old man with schizophrenia experienced worsening insomnia 10 days before admission. Thus, haloperidol was increased from 1.5 mg to 3 mg once daily, and 2 to 3 days later, he developed hand tremors and weakness. One day prior to admission, the patient suddenly developed severe back pain. Based on the examination, the patient was diagnosed with COVID-19 complicated with rhabdomyolysis. Laboratory findings on admission were as follows: creatine phosphokinase: 41 539 IU/L; urinary myoglobin, 190×10³ ng/mL; and hematuria scale, grade 4. On day 1, he was started on saline infusion; therefore, haloperidol was discontinued. On day 2, the hematuria resolved. On day 5, the tremor, weakness, and back pain had resolved. On day 7, his creatine kinase level was 242 IU/L, and saline was administered. CONCLUSIONS It has been suggested that the onset of COVID-19 can exacerbate haloperidol-induced rhabdomyolysis. Therefore, if there is a complication of rhabdomyolysis and COVID-19, it is important to review the drug history, specifically that of haloperidol. We recommend hydration and discontinuation of haloperidol to avoid acute kidney injury, in addition to treating COVID-19.

Factors associated with the risk perception of COVID-19 infection and severe illness: A cross-sectional study in Japan.

Understanding COVID-19 risk perception may help inform public health messaging aimed at encouraging preventive measures and improving countermeasures against the pandemic. We conducted an online survey of 29,708 Japanese adults in February 2021 and estimated the associations between COVID-19 risk perception and a broad array of individual factors. Two logistic regressions were constructed to estimate factors associated with the risk perception of COVID-19 (defined as responding that one might become infected within the next 6 months), and of severe illness among those who responded that they might become infected (defined as responding that one would become severely ill). After adjusting for covariates, those with a higher perceived risk of the COVID-19 vaccine had higher odds of risk perception for both infection and severe illness. Interestingly, those with higher odds of risk perception of being infected were more likely to report obtaining their information from healthcare workers whereas those with lower odds were more likely to report obtaining their information from the Internet or the government; those with lower odds of risk perception of being severely ill were more likely to report obtaining their information from the Internet. The higher the trust level in the government as a COVID-19 information source, the lower the odds of both risk perception of being infected and becoming severely ill. The higher the trust levels in social networking services as a COVID-19 information source, the higher the odds of risk perception of becoming severely ill. Public health messaging should address the factors identified in our study.