Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence, Japan, 2023.

We assessed SARS-CoV-2 seroprevalence in Japan during July-August 2023, with a focus on 2 key age groups, 0-15 and >80 years. We estimated overall seroprevalence of 45.3% for nucleocapsid antibodies and 95.4% for spike antibodies and found notable maternally derived spike antibodies in infants 6-11 months of age (90.0%).

Impairment of Social-Related Quality of Life in COVID-19 Pneumonia Survivors: A Prospective Longitudinal Study.

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients' health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Hemophagocytic syndrome due to Epstein-Barr virus and cytomegalovirus coinfection in a patient on adalimumab.

INTRODUCTION: Hemophagocytic syndrome (HPS) is a rare but potentially fatal complication of viral infections. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) often infect patients receiving TNF-alpha inhibitors (TNF-α inhibitors). While EBV and CMV are well established infections for the development of infectious mononucleosis, coinfection with EBV and CMV is common among immunosuppressed patients and can result in a fatal course. In addition, such viral infections can cause HPS. To the best of our knowledge, we present here the first report of HPS induced by EBV and CMV coinfection during anti-TNFα inhibitor use. CASE REPORT: A 23-year-old man hospitalized with fever, elevated liver enzymes, lymphadenopathy, and hepatosplenomegaly was diagnosed with HPS associated with EBV and CMV coinfection while using adalimumab. No clinical improvement was observed after discontinuation of adalimumab. HPS complicated by EBV and CMV coinfection was finally diagnosed, and immediate administration of ganciclovir and prednisone was considered to have prevented a lethal clinical outcome. CONCLUSION: For cases showing unexplained fever, elevated liver enzymes, and lymphadenopathy while using anti-TNFα inhibitors, screening for EBV and CMV coinfection should be encouraged. In addition, HPS should be considered in patients with EBV and/or CMV infection receiving anti-TNFα inhibitors to facilitate early definitive therapy.

Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19.

BACKGROUND: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. OBJECTIVE: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. MATERIALS AND METHODS: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. RESULTS: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. CONCLUSION: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.

Infectious Disease Emergency Specialist (IDES) Training Program in Japan: an innovative governmental challenge to respond to global public health emergencies.

In 2015, Japan created a unique governmental program to train experts in health emergencies called Infectious Disease Emergency Specialist (IDES). This is a concept paper to set out the goal and structure of the program, and to describe the achievement and the way forward to further contribute to global health security. The IDES program background, mission, structure, achievement, and future directions were reviewed and discussed by the IDES trainees, graduates, and program coordinators/supervisors. Since 2015, thirteen Japanese medical doctors have graduated from the program while five are currently in training. The IDES core competencies were identified in the context of a wide range of skillsets required for health emergencies. A large national and global network has been created through the training. Coordinated work with surge capacity of experts is of paramount importance to prepare for and respond to public health emergencies. The IDES program can be a good model to many other governments, and contribute to global health security.

Loiasis in a Japanese Traveler Returning from Central Africa.

We encountered a probable case of loiasis in a returned traveler from Central Africa. A 52-year-old Japanese woman presented to our hospital complaining of discomfort in her eyes and skin. She reported having frequently visited Central Africa over many years and having been extensively exposed to the rainforest climate and ecosystem. Although no microfilariae were found in her blood, there was an elevated level of IgG antibodies against the crude antigens of Brugia pahangi, which have cross-reactivity with Loa loa. She was treated with albendazole for 21 days, after which the antigen-specific IgG level decreased and no relapse occurred.

Parvimonas micra as a causative organism of spondylodiscitis: a report of two cases and a literature review.

Spondylodiscitis caused by Parvimonas micra, a rarely reported infection, might be under-detected using conventional methods. This report of the detection and treatment of two cases of spondylodiscitis due to P. micra and review of the literature indicates that the use of gene sequencing methods might improve the accuracy of diagnosing this infection.

Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: case report and literature review.

Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-year-old homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139(th) day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases.

Advantage of IFN-beta/alpha2b same-day administration for ribavirin-intolerant patients with chronic hepatitis C.

AIM: Although interferon (IFN)/ribavirin is the mainstream combination treatment for chronic hepatitis C in patients with a high viral load, ribavirin is problematic for women of childbearing age and patients with anemia. Therefore we needed to establish a new regimen without ribavirin. METHODS: We devised a new regimen (same-day beta/alpha2b) to administer IFN-beta and alpha2b on the same-day, and compared it with IFN-alpha2b alone and IFN-alpha2b plus ribavirin. The cases were 36 patients (26.1%) in whom ribavirin could not be used (young women, anemia, etc.) among 138 patients who underwent IFN treatment after ribavirin release. RESULTS: The percentages of patients withdrawing due to side-effects were 6.8%, 18.8% and 17.0% in the treatment with same-day beta/alpha2b, IFN-alpha2b alone and IFN-alpha2b plus ribavirin groups, respectively. In genotype 1b, the sustained viral response (SVR) was 28.6% (4/14), 13.6% (3/22) and 25.0% (8/32) with a high viral load, and 91.7% (11/12), 27.3% (3/11) and 57.1% (4/7) with a low viral load for the respective groups. According to a study on viral half-life during the early phase of IFN therapy, there was no difference among the regimens of same-day IFN-beta/alpha2b, beta alone, alpha2b alone and twice-daily treatment with IFN-beta. Same-day beta/alpha2b treatment showed a significantly higher SVR rate in moving type patients with a genotype 1b/high viral load. CONCLUSIONS: Same-day beta/alpha2b treatment resulted in few cases where therapy was discontinued and showed a high SVR rate. This regimen is especially appropriate in cases where ribavirin has been deemed unsuitable.

Prospective study on early virologic response to treatment with interferon alpha-2b plus ribavirin in patients with chronic hepatitis C genotype 1b.

To evaluate the predictive value of early virologic response (EVR) of achieving a sustained virologic response (SVR), an open, prospective trial including 42 patients with chronic hepatitis C genotype 1b was performed with directly observed 24-week treatment with interferon alpha-2b plus ribavirin. We assessed the predictive values of EVR at days 3, 7, 14, and weeks 4, 8, and 12 of the SVR. The SVR in an intention-to-treat analysis was 19.0%. Patients who reached SVR presented a significantly faster reduction in plasma viral load. Stepwise multiple logistic regression analysis of the factors (gender, age, IFN dosage, ribavirin dosage, HCV RNA, ISDR, and loss of HCV RNA at week 4) revealed that loss of HCV RNA at week 4 was the only independent variable of treatment outcome (P=0.0039). A viral load at treatment day 3 above 100kIU/ml, at day 7 above 50kIU/ml, and at day 14 above 10kIU/ml was 100% predictive for virologic non-response in all except 1 patient. The cutoff levels for HCV RNA at days 3 and 14 of treatment were associated with an algorithm of the failure to detect HCV RNA after 12 weeks of treatment. In conclusions, a very early virologic response assessment could be useful for prediction of later outcome of combination therapy in chronic hepatitis C genotype 1b.

Erectile dysfunction in patients with chronic viral liver disease: its relevance to protein malnutrition.

BACKGROUND: In patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD. METHODS: A total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed. RESULTS: The incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P < 0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50-59, and in 100% aged over 60 (P, overall <0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P < 0.05). Simple regression analysis showed age (P < 0.01), physical function (P < 0.001), role physical (P < 0.001), and social functioning (P < 0.05) on the SF-36, and serum albumin (P < 0.001) as significant determinants of ED. Multiple regression analysis identified age (P < 0.001) and serum albumin (P < 0.001) as independent significant factors that determined ED. CONCLUSIONS: These data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.

Psychoneurological symptoms during interferon therapy in patients with chronic hepatitis: prospective study on predictive use of Cornell Medical Index and electroencephalogram.

BACKGROUND/AIMS: We assessed the usefulness of the Cornell Medical Index (CMI) and electroencephalogram (EEG) in the prediction and early detection of psychoneurological symptoms associated with interferon (IFN) therapy for chronic viral hepatitis. METHODS: Forty-eight consecutive patients received IFN for chronic viral hepatitis for 8-24 weeks. CMI was measured before IFN therapy. Serial EEGs were recorded before IFN therapy, 2, 4 weeks, and thereafter every 4 weeks in the therapy. RESULTS: Psychoneurological symptoms including insomnia, depression, and restlessness were seen in 11 (23%) of 48 patients. Five (13%) of 40 patients with CMI I and II and six (75%) of eight with CMI III developed psychoneurological symptoms (P<0.001). Sensitivity, specificity, and predictive accuracy of CMI III were 55%, 95%, and 75%, respectively. Abnormal EEG such as slow basic rhythm, appeared in 13 patients (27%) during IFN therapy. Psychoneurological symptoms were seen in six (46%) of the 13 patients with abnormal EEG, and in five (14%) of 35 in whom EEG remained normal (P<0.05). CONCLUSIONS: CMI is useful for the prediction of IFN-induced psychoneurological symptoms in patients with chronic viral hepatitis. Serial EEGs contribute to the screening and auxiliarily assessing the adverse effects of IFN on the central nervous system.

Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: comparison with daytime administration.

BACKGROUND: In an attempt to optimize oral branched-chain amino acid (BCAA) administration to improve serum albumin in cirrhotic patients, we compared the effects of nocturnal and daytime BCAA administration on protein metabolism in cirrhotic patients. METHODS: Twelve cirrhotic patients were enrolled in a short-term study. Patients were administered either conventional daytime BCAA granule or nocturnal BCAA for a week, and metabolic analyses were performed, followed by a crossover study in the next week. Another 12 patients, who showed no improvement of serum albumin level with previous daytime BCAA administration, were randomly assigned to either a nocturnal or a daytime BCAA administration group in a long-term study. RESULTS: Low Fischer's ratio, reduced respiratory quotient, and low serum albumin were observed at entry in cirrhotic patients. Whereas daytime BCAA administration improved nitrogen balance and Fischer's ratio, these 2 were further significantly improved after nocturnal BCAA administration. There were no changes in parameters of energy metabolism throughout the study. In the 3-month follow-up, a significant increase in serum albumin was observed in patients administered nocturnal BCAA but not in those administered daytime BCAA. CONCLUSIONS: Nocturnal BCAA administration improved serum albumin in cirrhotic patients who showed no improvement in serum albumin level with daytime BCAA administration. This effect could be partly caused by the improved protein sparing with this administration method.