Serological Screening of Immunoglobulin G against SARS-CoV-2 Nucleocapsid and Spike Protein before and after Two Vaccine Doses among Healthcare Workers in Japan.

This study sought to evaluate the effects of two vaccine doses and the extent of SARS-CoV-2 infection among healthcare workers. We measured immunoglobulin G antibody titers against SARS-CoV-2 nucleocapsid and spike protein among healthcare workers at Gunma University Hospital. In March 2021, prior to BNT-162b2 vaccination, two of 771 participants were seropositive for nucleocapsid and spike protein, whereas 768 were seronegative. The remaining one participant was seropositive for nucleocapsid protein but seronegative for spike protein. A total of 769 participants were seropositive for spike protein after two vaccination doses. The two seropositive participants prior to vaccination showed the highest antibody titers after the second vaccination. They were probably infected with SARS-CoV-2 without clinical symptoms before March 2021. Four weeks after the second vaccination, a younger age was associated with higher antibody titers against SARS-CoV-2 spike protein. Thirty-two weeks after the second vaccination, blood samples were collected from 342 of 769 participants. Antibody titers at 32 weeks after the second vaccination significantly decreased compared with those at 4 weeks after the second vaccination among all age groups. The rate of decrease in antibody titers between 4 and 32 weeks after the second vaccination was greater in the female participants. No sex differences were observed in the antibody titers within each age group. BNT-162b2 vaccination thus induced seroconversion in an age-dependent manner. Serological screening could further establish the likelihood of subclinical SARS-CoV-2 infection.

Vaccination Status and Antibody Titers against Rubella and Measles among Japanese Female College Students Majoring in Childcare between 2015 and 2018.

In 2014, for the protection of medical workers against measles and rubella infection, the Japanese Society for Infection Prevention and Control (JSIPC) recommended either maintaining antibody titers of seroprotective range or two-dose vaccination. JSIPC defined antibody titers into 3 ranges: seroprotective as expected prevention of infection, seronegative as under detection levels, and seropositive as antibody titers ranged between seronegative and seroprotective. This study aimed to explore the association between the number of vaccine doses received and the antibody titers against measles and rubella among Japanese college students majoring in childcare. A total of 841 female students with no history of measles or rubella were serologically screened at the time of college admission between 2015 and 2018. All 841 students had been vaccinated against measles; 738 (87.8%) received two doses of the measles vaccine and 103 (12.2%) received one dose. Likewise, 839 students, except for two, had been vaccinated against rubella; 719 (85.7%) received two doses of the rubella vaccine and 120 (14.3%) received one dose. We thus found that 107 students (12.7%) were seropositive for measles-specific IgG and 731 (86.9%) attained seroprotective titers. By contrast, in case of rubella-specific IgG, only 462 students (55.1%) attained seroprotective titers, and 371 students (44.1%) were seropositive. The two students without receiving rubella vaccination were classified as seronegative. In conclusion, despite that > 85% of students surveyed had received two doses of measles and rubella vaccines, a substantial number of students remain susceptible to measles and especially rubella at the time of college admission.

Intramedullary spinal cord abscess involving Actinomyces and Streptococcus: a case report and literature review.

INTRODUCTION: Intramedullary spinal cord abscesses (ISCA) are rare and caused by central nervous system infections. Although polymicrobial infections are rarely seen in ISCAs, isolation of the causative pathogen is important for treatment. Here, we describe a very rare case of ISCA resulting from a mixed Streptococcus and Actinomyces infection. CASE PRESENTATION: An 82-year-old man presented with acute posterior cervical pain and progressive quadriplegia. Radiological investigations revealed a mass lesion showing marginal enhancement at the level of the C3-4 vertebrae. Microsurgical drainage was performed, and Streptococcus and Actinomyces were identified as causative agents. Subsequent antibiotic treatment was noted to be beneficial to the patient. DISCUSSION: This case suggests that mixed infection can develop into ISCA depending on the causative agents such as Actinomyces. Prompt pathogen-directed antibacterial therapy is required for ISCA treatment.

Tuberculosis screening using a T-cell interferon-γ release assay in Japanese medical students and non-Japanese international students.

Screening of medical students and international students for tuberculosis (TB) at the time of admission is a key strategy to control and prevent the spread of infection on university campus and teaching hospitals because of the high risk of exposure to TB patients. The Mycobacterium tuberculosis antigen-specific T-cell interferon-γ release assays (IGRAs) are specific latent tuberculosis detection methods used in such groups. Currently, in Japan, there are no guidelines and no baseline data on IGRAs to evaluate the risk of TB in these high-risk groups. In order to evaluate TB risk at the time of admission in university campus and medical schools in Japan, a retrospective study was conducted. A total of 969 students (585 Japanese students and 384 international students) were screened for TB using the IGRAs at the time of admission. Eight Japanese students (0.9%) were positive for IGRAs, but none were diagnosed with active TB at the follow-up. In contrast, 30 international students (7.8%) were positive for IGRAs, including two students diagnosed with active TB during follow up. Positive ratio of IGRAs in international students was significantly higher than that of medical students at the time of admission. Here we propose a standard approach for TB screening with IGRAs at the time of admission for medical students and international students in Japan.

The Assessment of the Efficacy and Safety of Favipiravir for Patients with SARS-CoV-2 Infection: A Multicenter Non-randomized, Uncontrolled Single-arm Prospective Study.

Objective Among treatment options for coronavirus infectious disease 2019 (COVID-19), well-studied oral medications are limited. We conducted a multicenter non-randomized, uncontrolled single-arm prospective study to assess the efficacy and safety of favipiravir for patients with COVID-19. Methods One hundred participants were sequentially recruited to 2 cohorts: cohort 1 (Day 1: 1,600 mg/day, Day 2 to 14: 600 mg/day, n=50) and cohort 2 (Day 1: 1,800 mg/day, Day 2 to 14: 800 mg/day, n=50). The efficacy endpoint was the negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the odds ratio (OR) of cohort 2 to cohort 1 for negative conversion on Day 10 was calculated. Characteristics of all participants and profiles of adverse events (AEs) were collected and analyzed. Results The mean age of participants was 62.8±17.6 years old. Thirty-four patients (34.0%) experienced worsening pneumonia, 7 (7.0%) were intubated, and 4 (4.0%) died during the observation period. Cohort 2 showed a higher negative conversion rate than cohort 1 [adjusted OR 3.32 (95% confidence interval (CI), 1.17 to 9.38), p=0.024], and this association was maintained after adjusting for the age, sex, body mass index, and baseline C-reactive protein level. Regarding adverse events, hyperuricemia was most frequently observed followed by an elevation of the liver enzyme levels (all-grade: 49.0%, Grade ≥3: 12.0%), and cohort 2 tended to have a higher incidence than cohort 1. However, no remarkable association of adverse events was observed between patients <65 and ≥65 years old. Conclusion The antiviral efficacy of favipiravir was difficult to interpret due to the limitation of the study design. However, no remarkable issues with safety or tolerability associated with favipiravir were observed, even in elderly patients with COVID-19.

Antibacterial activity of carbapenems against clinical isolates of respiratory bacterial pathogens in the northeastern region of Japan in 2007.

As the increasing prevalence of resistant strains of respiratory bacterial pathogens has recently been reported, continuous monitoring of the susceptibility of clinical isolates to antibacterial agents is important. We performed a surveillance study focusing on the susceptibility of major respiratory bacterial pathogens in the northeastern region of Japan to carbapenems and control drugs. A total of 168 bacterial strains isolated from patients with respiratory tract infections in 2007 were collected and the minimum inhibitory concentration (MIC) determined. MIC data were subjected to pharmacokinetic/pharmacodynamic analysis with Monte Carlo simulation to calculate the probability of achieving the target of time above MIC with each carbapenem. All Moraxella catarrhalis, Streptococcus pneumoniae, and methicillin-sensitive Staphylococcus aureus isolates were susceptible to carbapenems. Despite the increasing prevalence of ß-lactamase-nonproducing ampicillin-resistant strains, all Haemophilus influenzae isolates were susceptible to meropenem. For Pseudomonas aeruginosa, the susceptibility rates for meropenem and biapenem were 76.7%, and the highest probability of achieving pharmacodynamic target (40% of the time above MIC) was obtained with meropenem 0.5 g three times daily as a 4-h infusion (89.4%), followed by meropenem 0.5 g four times daily as a 1-h infusion (88.4%). Carbapenems have retained their position as key drugs for severe respiratory tract infections.

Erythema nodosum-like eruption in coronavirus disease 2019: A case report and literature review of Asian countries.

In the worldwide coronavirus disease 2019 (COVID-19) outbreak, skin manifestations were seen in COVID-19 patients. We report a case in which a COVID-19 patient developed cutaneous lesions that were diagnosed as erythema nodosum-like lesions, which were associated with COVID-19. Nasopharyngeal swab polymerase chain reaction (PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathologically, extensive inflammation was seen from the epidermis to the fat tissue. An organized thrombus and disrupted inner elastic lamina were seen in an intradermal vessel. These findings suggest septal panniculitis with cutaneous polyarteritis nodosa. The results of PCR using the specimen of skin lesion was negative. The patient took non-steroidal anti-inflammatory drugs and the skin lesion improved in 3 weeks. To characterize the skin eruption, we reviewed previous reports on COVID-19 (confirmed by the detection of SARS-CoV-2 infection) from Asian countries. The type of eruption and timing of its appearance in this case seemed rare. Differences in skin manifestations between Western and Asian countries were noted.

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. METHODS: COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. RESULTS: A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. CONCLUSIONS: The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION: Clinicaltrials.jp number: JapicCTI-205238.

Improvement of Severe COVID-19 in an Elderly Man by Sequential Use of Antiviral Drugs.

Although a variety of existing drugs are being tested for patients with coronavirus disease 2019 (COVID-19), no efficacious treatment has been found so far, particularly for severe cases. We report successful recovery in an elderly patient with severe pneumonia requiring mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Despite administration of multiple antiviral drugs, including lopinavir/ritonavir, chloroquine, and favipiravir, the patient's condition did not improve. However, after administration of another antiviral drug, remdesivir, we were able to terminate invasive interventions, including ECMO, and subsequently obtained negative polymerase chain reaction results. Although further validation is needed, remdesivir might be effective in treating COVID-19.

Comparison of 16S ribosomal RNA gene sequence analysis and conventional culture in the environmental survey of a hospital.

BACKGROUND: Nosocomial infection is one of the most common complications within health care facilities. Certain studies have reported outbreaks resulting from contaminated hospital environments. Although the identification of bacteria in the environment can readily be achieved using culturing methods, these methods detect live bacteria. Sequencing of the 16S ribosomal RNA (16S rRNA) gene is recognized to be effective for bacterial identification. In this study, we surveyed wards where drug-resistant bacteria had been isolated and compared conventional culture methods with 16S rRNA gene sequencing methods. METHODS: Samples were collected using sterile swabs from two wards (northern and southern) at Gunma University Hospital contaminated by Acinetobacter sp.. We extracted DNA directly from the swabs. Following extraction, the DNA was amplified using polymerase chain reaction (PCR). The PCR products were cloned using the plasmid vector. The plasmid DNA were sequenced, and identification were performed using database. 16S rRNA gene sequence analyses were compared conventional culture methods. RESULTS: In the northern ward, Acinetobacter sp. was detected from only two of 14 samples using the culture method. In contrast, 16S rRNA gene sequencing analysis detected Acinetobacter sp. from seven of 14 samples. Drug-resistant Acinetobacter sp. was isolated from bathrooms of the southern ward and was detected from four of seven samples using the culture method in comparison with six of seven samples by 16S rRNA gene sequencing analysis. CONCLUSIONS: Molecular biological analysis showed a higher sensitivity to detect specific bacteria and detected a greater number of species than the culture method. Our results suggest that 16S rRNA gene sequencing analysis is useful to identify range of contamination which were not found in conventional culture method. When a nosocomial outbreak cannot be adequately controlled, molecular biological analysis may serve as a useful tool for environmental surveys in hospitals.

Metallo-ß-lactamase-producing Klebsiella pneumoniae infection in a non-hospital environment.

Case: A 92-year-old female resident at a nursing home was transported to the emergency department unconscious, hypotensive, and febrile. Chest X-rays and computed tomography revealed a permeation shadow in the right lung. The patient was diagnosed with sepsis due to pneumonia. At the time of admission, she had not received antibiotics or treatment using medical devices over the past 6 months. Two sets of samples were taken for blood and sputum cultures, and Klebsiella pneumoniae was isolated from all cultures. The strain was identified as metallo-ß-lactamase-producing K. pneumoniae, and the patient was successfully treated with tazobactam-piperacillin. This case indicates that metallo-ß-lactamase-producing K. pneumoniae infection occurred in a non-hospital environment. Outcome: After tazobactam-piperacillin treatment, the patient was transferred to another hospital. Conclusion: Emergency physicians should be aware of multidrug-resistant bacterial infection even in a non-hospital setting.

Mannose-binding lectin gene polymorphism is a modulating factor in repeated respiratory infections.

STUDY OBJECTIVE: To clarify how mannose-binding lectin (MBL) participates in the pulmonary defense system. DESIGN: Multicenter retrospective study. PARTICIPANTS: Sixty-two patients with unexplained recurrent respiratory infections, 50 patients with nontuberculous mycobacterial infection, 23 patients with aspergillosis, and 49 patients with diffuse panbronchiolitis (DPB). For controls, 52 blood samples were provided by the Blood Donation Center of the Japanese Red Cross Society. For BAL fluid (BALF) evaluation, there were five patients with acute phase pneumonia and five healthy volunteers. MEASUREMENT AND RESULTS: We demonstrated that MBL protein could be directly measured in the BALF from the lungs of patients with pneumonia by means of enzyme-linked immunosorbent assay. Furthermore, we demonstrated that the prevalence of the codon 54 mutation of the MBL gene in 62 patients having repeated respiratory infections was significantly higher compared with healthy control subjects (54.8% vs 32.7%). The prevalence of the MBL mutant genotype among patients with DPB was higher (51.1%) than in the rest of the patients. In contrast, the prevalence of the MBL mutant genotype among patients with nontuberculous mycobacteria or Aspergillus chronic infection was not significantly different from that in control subjects (44.0% and 34.8%). CONCLUSIONS: Our results suggest that MBL may play an important role in modulating the inflammatory response against repeated microbial infections.

Prevalence of community-acquired respiratory tract infections associated with Q fever in Japan.

A multicenter prospective cohort study to assess the occurrence and characteristics of acute Q fever associated with community acquired respiratory infections was performed. Among the 400 patients enrolled for the study, 10 (2.50%) patients (5 out of 120 cases of pneumonia, 3 out of 131 cases of acute bronchitis, and 2 out of 149 cases of upper respiratory infections) were diagnosed as having acute Q fever. Contact with dogs or cats before the onset of the disease was confirmed in most of the patients. The clinical profiles of these 10 patients were generally similar to those reported from other countries, such as fever, general fatigue and liver dysfunction, except for the predominance of sporadic cases among the urban population. Our study demonstrates that Q fever is not uncommon cause of community-acquired respiratory infections even in Japan.