Kazuko Yamamoto

Introduction: Following the reclassification of COVID-19 as a category V infectious disease in Japan in May 2023, systematic public health monitoring of case numbers and cluster outbreaks was discontinued. Consequently, infection control measures, responses to cluster outbreaks and vaccination coverage in long-term care facilities were largely left to the discretion of individual facilities, and the understanding of the current situation in these settings remains insufficient. This observational study aims to retrospectively investigate COVID-19 cluster outbreaks and the resulting burdens experienced by facilities after reclassification, focusing on special nursing homes (Tokubetsu Yogo Rojin Home) for older adults, a population at particularly high risk for COVID-19-associated hospitalisation and mortality. By comprehensively evaluating facility and resident characteristics, vaccination coverage and infection prevention and control measures, this study seeks to generate evidence to inform future infection control strategies in long-term care facilities. Methods and analysis: This retrospective observational study targets special nursing homes in Okinawa Prefecture and residents living in these facilities. Data for a target sample of nine nursing homes with approximately 900 residents will be collected from existing facility and medical records using the Research Electronic Data Capture system. The study was initiated in June 2025 and completion is anticipated by March 2027. The primary outcomes are the occurrence of COVID-19 cluster outbreaks in nursing homes between May 2023 and August 2025 and the facility-level burden experienced during outbreaks, including operational and economic impacts. A cluster outbreak is defined as the occurrence of ≥2 cases of the same infectious disease within a 10-day period. Key variables of interest include baseline characteristics of facilities and residents, vaccination coverage among staff and residents and infection prevention and control measures. Additionally, the study explores potential factors associated with residents’ clinical outcomes and facility burden using logistic and linear regression models, respectively, with facility-level random intercepts if deemed appropriate. Prespecified supplementary analyses include one-way analysis of variance and χ ² tests. Ethics and dissemination: The study protocol was approved by the Institutional Review Board of the University of the Ryukyus in June 2025 (approval number: 25-2486-00-00-00). The findings will be disseminated at academic conferences and in peer-reviewed medical journals.

Background: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator. Objectives: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease. Design: An exploratory, multicenter, randomized-controlled, open-label trial. Methods: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations. Results: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C ( p = 0.08), and fatigue significantly decreased in group A ( p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A. Conclusion: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia. Trial registration: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011 ) on April 13, 2021.

Study Protocol Influence of PAI-1 gene polymorphism on the effectiveness of tezepelumab in individuals with severe asthma: a study protocol for a prospective, non-randomized, interventional, comparative trial Susumu Fukahori, Yasushi Obase, Chizu Fukushima, Kosuke Kosai, Katsunori Yanagihara, Shintaro Hara, Shinya Tomari, Hironobu Tsubouchi, Taiga Miyazaki, Nobuko Matsuo, Ayako Matsuo, Nobuhiro Matsumoto, Hiromi Ide, Kazunori Tobino, Norio Kodaka, Hiroto Matsuse, Wakako Arakaki, Shusaku Haranaga, Kazuko Yamamoto, Hiroyuki Yoshimine, Hideki Sakakibara, Kazuhiro Yatera, Hiroki Tashiro, Koichiro Takahashi, Daisuke Himeji, Hiroshi Mukae

Introduction Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still an ongoing public health threat. COVID-19 can be accompanied by prolonged symptoms, known as “long COVID”, however, no pharmaceutical treatments are currently available for these symptoms. Lactococcus lactis strain Plasma (LC-Plasma; Lactococcus lactis subsp. lactis JCM 5805) directly activates human plasmacytoid dendritic cells (pDCs) and triggers antiviral immune responses. We hypothesized that LC-Plasma reduced SARS-CoV-2 viral load and eased symptoms in patients with mild COVID-19. Methods This PLATEAU study enrolled 100 patients with mild COVID-19 during Omicron BA.1 endemic, who were randomized into the LC-Plasma or placebo group in a 1:1 ratio and were observed for 14 days. The primary endpoint was change in total score of eight subjective symptoms (fatigue, anorexia, headache, cough, shortness of breath, chest pain, smell, and taste disturbance). Secondary endpoints included each symptom, SARS-CoV-2 viral load, and pDCs. Results The primary endpoint did not show between-group differences. However, the proportion of patients without smell and taste disturbances was significantly higher in the LC-Plasma group on day 13 (p = 0.030). The LC-Plasma group showed a significantly earlier decrease in SARS-CoV-2 viral load on day 4 (p < 0.001) and an increase in pDCs on day 8 (p = 0.0498). Mild adverse events, such as diarrhea, cough-variant asthma, and urticaria, occurred in three (5.9%) patients in the LC-Plasma group. Conclusions The intake of LC-Plasma in patients with mild COVID-19 activates pDC, decreases SARS-CoV-2 viral load earlier, and may improve smell and taste disorders more quickly. LC-Plasma could be a safe, inexpensive, and easily accessible tool for the treatment of mild COVID-19. Trial Registration jRCTs071210097. Graphical Abstract

An association between coronavirus disease 2019 (COVID-19) and concomitant varicella-zoster virus (VZV) reactivation has been proposed. We herein report a case of severe VZV pneumonia in a 73-year-old man who underwent corticosteroid tapering after recovering from COVID-19 and presented with fever, vesicular rashes, and hypoxemia. Chest computed tomography (CT) revealed ground-glass opacities and multiple granular shadows. Varicella-zoster virus was detected in the skin and bronchoalveolar lavage fluid. The patient was diagnosed with disseminated VZV reactivation and thereafter successfully recovered with acyclovir treatment. Physicians should consider the possibility of VZV reactivation when ground-glass opacities or patchy nodular shadows appear during the course of patients with COVID-19.