Ensitrelvir eradicates persistent SARS-CoV-2 infection in a follicular lymphoma patient treated with anti-CD20 antibodies.

Patients with hematological malignancies, especially B-cell malignancies, who received anti-CD20 antibodies exhibit a poor immune response to the mRNA coronavirus disease 2019 (COVID-19) vaccine within 6-12 months after the last administration. These patients occasionally present with severe COVID-19 symptoms. Additionally, patients with hematologic diseases who have persistent COVID-19 after receiving anti-CD20 antibodies, postpone chemotherapy for the primary disease. Despite the efficacy of ensitrelvir in shortening the duration of symptoms, evidence of improved prognosis is lacking. However, prognosis might be improved if ensitrelvir treatment could reduce the viral load and shorten the time to postpone chemotherapy. It is unclear whether viral reduction directly improves prognosis. However, faster viral reduction may lead to faster resumption of chemotherapy for the underlying disease, resulting in better prognosis. Here, we present a case wherein we administered ensitrelvir fumaric acid to a 75-year-old woman with persistent COVID-19 after anti-CD20 antibody treatment. Her symptoms resolved quickly, with a reduction of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, and she could continue receiving chemotherapy for lymphoma. Our findings suggest that ensitrelvir administration should be considered in patients with SARS-CoV-2 infection after anti-CD20 antibody treatment.

Frequency and Risk Factors for Persistent and Concomitant Symptoms after Hospital Discharge for Coronavirus Disease 2019 in the Pre-omicron Period: An Exploratory Longitudinal Study.

Introduction: Many countries have reported persistent and concomitant symptoms of coronavirus disease 2019 (COVID-19). This study aimed to identify persistent COVID-19 and concomitant symptoms in discharged patients and identify the risk factors for such symptoms. Methods: This study enrolled patients with COVID-19 who were admitted to the University of Fukui Hospital, Japan, and discharged between April 3, 2020, and August 19, 2021. Persistent and concomitant symptoms were confirmed based on medical examinations approximately 2 weeks after discharge. Patient characteristics and symptoms were collected from the patients' medical records by a technical assistant. Results: This study included 120 patients (60 men and 60 women; mean age, 53.5 ± 17.0 years). Persistent COVID-19 symptoms were observed in 62 patients (51.7%). The most common persistent symptom was weakened physical function, manifesting as physical weakness (48.4%) and muscle weakness (29.0%). Binary logistic regression analysis revealed that cough with expectoration within the acute phase of COVID-19 was a risk factor predisposing patients to COVID-19 sequelae (odds ratio: 2.94, 95% confidence interval: 1.300 - 6.630, p = 0.009). Conclusions: The study findings suggest that productive cough in the acute phase is associated with subsequent physical and muscle weaknesses in the subacute phase.

Infection rate among close contacts of patients with coronavirus disease in Japan: a descriptive study and literature review.

Background: In Japan, on April 20, 2020, the definition of a close contact regarding coronavirus disease (COVID-19) was changed from a long-term contact time to a specified contact time of 15 min and from a contact distance of 2 m to 1 m. Objectives: We aimed to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate among close contacts of patients with COVID-19 and determine the impact of the infection on transmission among close contacts. Methods: The numbers of SARS-CoV-2 tests, SARS-CoV-2-positive cases, and close contacts of patients with COVID-19 were assessed between March 2020 and February 2021 in Fukui Prefecture, Japan. The study period was subdivided into 3 periods. The second and third period contained data with the changed definition of close contact. Results: Overall, 32,238 SARS-CoV-2 tests were performed. There were 545 patients with COVID-19 and 1487 close contacts, of whom 267 tested positive. The highest infection rate occurred in period 3. Distance, protective measures, and contact time with COVID-19 patients influenced the increased infection rate. The infection rate showed a rising trend from 11.1% in period 1 to 19.2% and 20.0% in periods 2 and 3, respectively (Cochran-Armitage test; P < 0.004). Multivariate analysis revealed that female sex was an independent risk factor for infection of close contacts (odds ratio: 2.23; 95% confidence interval: 1.700-2.930). Conclusions: Female sex is a risk factor for transmission by close contacts. The rate of infection among close contacts may be associated with contact time, contact distance, and protective measures.

Posterior reversible encephalopathy syndrome (PRES) associated with SARS-CoV-2 infection in a patient under maintenance haemodialysis: a case report.

BACKGROUND: Endothelial dysfunction is common in patients undergoing chronic haemodialysis, and is a major cause of posterior reversible encephalopathy syndrome (PRES). Recently, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause endothelial dysfunction by infecting vascular endothelial cells. Several cases of neurological complications in patients without kidney dysfunction, and only a few cases in patients with chronic kidney disease, have been reported in the literature. However, no previous report has yet described PRES associated with SARS-CoV-2 infection among patients undergoing maintenance dialysis. CASE PRESENTATION: A 54-year-old woman undergoing maintenance haemodialysis was admitted to our hospital for status epilepticus. She had developed end-stage kidney disease (ESKD) secondary to diabetic nephropathy. Seven days prior to admission, she had developed fever and was diagnosed with COVID-19. Subsequently her blood pressure increased from 160/90 mmHg to 190/100 mmHg. On admission, she presented with severe hypertension (> 220/150 mmHg), unconsciousness, and epilepticus. CT tomography revealed no signs of brain haemorrhage. Cranio-spinal fluid (CSF) examination revealed no signs of encephalitis, and CSF polymerase chain reaction (PCR) for SARS-CoV-2 was negative. MRI findings revealed focal T2/FLAIR hyperintensity in the bilateral parietooccipital regions, leading to the diagnosis of PRES. Deep sedation and strict blood pressure control resulted in a rapid improvement of her symptoms, and she was discharged without sequelae. CONCLUSIONS: We report the first case of PRES associated with SARS-CoV-2 infection in a patient undergoing maintenance haemodialysis. Patients undergoing maintenance haemodialysis are at high risk of PRES because of several risk factors. SARS-CoV-2 infection causes direct invasion of endothelial cells by binding to angiotensin-converting enzyme 2 (ACE2), initiating cytokine release, and hypercoagulation, leading to vascular endothelial cell injury and increased vascular leakage. In the present case, SARS-CoV-2 infection possibly be associated with the development of PRES.

Exploration of sepsis assisting parameters in hospital autopsied-patients: a prospective study.

Although Sepsis-3 doesn't require evidence of bacteremia to diagnose sepsis, clinicians often want to identify the causative pathogen at autopsy. In principle, if the blood cultures are the same at ante- and postmortem, the cause of death is obvious. However, interpretations of postmortem blood cultures are often difficult due to discordance, negativity, mixed infection, and contamination, of pathogens occupying ≥ 50% of the tests. To increase specificity identifying agonal phase sepsis in the situations where blood cultures are discordant, multiple or negative at postmortem, we established a scoring system using blood cultures, procalcitonin (PCN) showing highest sensitivity and specificity for postmortem serum, and bone marrow polyhemophagocytosis (PHP). Histological sepsis showed significantly higher levels of culture score (2.3 ± 1.5 vs. 0.4 ± 0.5, p < 0.001), PHP score (2.5 ± 0.8 vs. 1.0 ± 1.1, p < 0.001), and PCN score (1.8 ± 0.8 vs. 0.8 ± 0.6, p < 0.01) than non-septic patients. Receiver operating characteristic curve analysis indicated that estimation of three scores was the most reliable indicator for recognizing agonal phase sepsis. These findings suggest that the combination of these three inspections enables to determine the pathological diagnoses of sepsis even it is not obvious by discordant, mixed or negative blood cultures.

Antibody level dynamics until after the third dose of COVID-19 vaccination.

The antibody titers of volunteers, including elderly people, were investigated after the second dose of the BNT162b2 vaccine (Pfizer-BioNTech) as an mRNA vaccine against the coronavirus disease 2019 (COVID-19). Serum samples were collected from 105 volunteers (44 healthcare workers and 61 elderly people) 7-14 days after the second vaccine dose, and antibody titers were measured. The antibody titers of study participants in their 20s were significantly higher than those of other age groups. Furthermore, the antibody titers of participants aged <60 years were significantly higher than those of participants aged ≥60 years. Serum samples were repeatedly collected from 44 healthcare workers until after the third vaccine dose. Eight months after the second round of vaccination, the antibody titer levels decreased to the same level as that before the second vaccine dose. After the third booster vaccination, the antibody titer recovered to the same level as that after the second dose. Neutralizing activities were also investigated at four time points before and after the second vaccine dose. The antibody titers and neutralizing activity were positively correlated. Therefore, neutralizing activity can be predicted by measuring the antibody titer. In conclusion, the antibody titers in the elderly population were significantly lower than those in the younger population. Although the antibody titers increased following vaccination, their levels showed a decline after several months, returning to the same level as that after a single dose of mRNA vaccination. The antibody titer levels recovered after the third dose of vaccination, which had already been administered in Japan. Routine administration of vaccine should be considered in the future.

Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series.

OBJECTIVES: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study. METHODS: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups. RESULTS: The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4. CONCLUSIONS: Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.

Histology and cytokine levels in hepatic injury accompanying a case of non-severe COVID-19.

The pathogenesis of liver dysfunction that complicates coronavirus disease 2019 (COVID-19) remains unclear, especially in mild to moderate severity cases. In this case, a novel coronavirus infection was detected by polymerase chain reaction (PCR) in a 76-year-old woman hospitalized after presenting with fever. No other abnormal physical findings were observed, and oxygen administration was not required. Chest computed tomography (CT) showed a ground-glass-like and an infiltrative shadow in the right lung, and moderate COVID-19 was diagnosed. Initially, the fever resolved, and PCR turned negative; however, the fever reappeared on hospitalization day 14, and CT showed pneumonia exacerbation accompanied by new onset of fatty liver. Biochemical testing revealed marked liver dysfunction, accompanied by elevated serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α levels. Physical findings and all laboratory parameters improved after conservative treatment, and she was discharged on day 22. A liver biopsy performed 44 days post-discharge showed T-cell-dominant inflammatory cell infiltration, mainly in the portal region. Some hepatocytes showed fatty degeneration.We report a case of moderate COVID-19 in which histological hepatitis persisted after a substantial period had passed since the initial infection had cleared and associated transaminase elevations had resolved, with a comparison of serum cytokine dynamics.

Droplets Adhesion to Surgical Masks during Standard Oral Surgery.

The most common routes of transmission of coronavirus disease 2019 are droplet and contact infections. During dental treatment, several instruments and procedures used generate droplets of saliva and blood, such as during the extraction of an impacted third molar (M3). Surgical masks are often used during tooth extraction. However, the surface structures of surgical masks against droplets are not fully understood. Therefore, we analyzed the droplets that adhered to the surgical masks during impacted M3 extraction using electron microscopy. The surgical mask was divided into three layers and observed using electron microscopy. The outer and inner layers had a similar mesh-like structure, whereas the middle layer had a denser three-dimensional structure. Droplets ranging from 20-100 µm in size, generated during the extraction, adhered to the fibers of the outer layer of the mask. Fewer droplets adhered to the middle layer than to the outer layer. Droplets did not reach the inner layer. In conclusion, we suggest that a surgical mask can prevent droplet infection when performing impacted M3 extraction. This study is expected to contribute to the study of infection control strategies during dental treatments in the future.

A longitudinal study of Candida bloodstream infections in a Japanese university hospital: species distribution, drug susceptibility, clinical features, and mortality predictors.

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Multifaceted efficacy of caspofungin against fungal infections in COVID-19 patients.

Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers Candida spp. and Aspergillus spp. as causative pathogens of fungal infections associated with COVID-19, and is known to have few side effects among antifungal drugs. Recent studies have shown that caspofungin is expected to inhibit the growth of severe acute respiratory syndrome coronavirus 2. In addition, the inhibitory effects of caspofungin on spleen tyrosine kinase-related intracellular signaling are anticipated to suppress the overproduction of proinflammatory cytokines and immune thrombosis, which are problems in severe COVID-19. Early use of caspofungin in patients with COVID-19 with hematological diseases or in the ICU may help prevent fungal infections and reduce severe cases in COVID-19 patients.

Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan.

OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Efficacy and Safety of Caspofungin Treatment in Febrile Neutropenic Patients with Hematological Disorders: A Multicenter Consecutive Case Series.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

Aseptic Meningitis after Amenamevir Treatment for Herpes Zoster in the First Branch of the Trigeminal Nerve.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.