Prediction of an increase in oxygen requirement of SARS-CoV-2 pneumonia using three different scoring systems.

INTRODUCTION: In patients with severe coronavirus disease 2019 (COVID-19), respiratory failure is a major complication and its symptoms occur around one week after onset. The CURB-65, A-DROP and expanded CURB-65 tools are known to predict the risk of mortality in patients with community-acquired pneumonia. In this retrospective single-center retrospective study, we aimed to assess the correlations of the A-DROP, CURB-65, and expanded CURB-65 scores on admission with an increase in oxygen requirement in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: We retrospectively analyzed 207 patients who were hospitalized with SARS-CoV-2 pneumonia at the Self-Defense Forces Central Hospital in Tokyo, Japan. Performance of A-DROP, CURB-65, and the expanded CURB-65 scores were validated. In addition, we assessed whether there were any associations between an increase in oxygen requirement and known risk factors for critical illness in COVID-19, including elevation of liver enzymes and C-reactive protein (CRP), lymphocytopenia, high D-dimer levels and the chest computed tomography (CT) score. RESULTS: The areas under the curve for the ability of CURB-65, A-DROP, and the expanded CURB-65 scores to predict an increase in oxygen requirement were 0.6961, 0.6980 and 0.8327, respectively, and the differences between the three groups were statistically significant (p < 0.001). Comorbid cardiovascular disease, lymphocytopenia, elevated CRP, liver enzyme and D-dimer levels, and higher chest CT score were significantly associated with an increase in oxygen requirement CONCLUSIONS: The expanded CURB-65 score can be a better predictor of an increase in oxygen requirement in patients with SARS-CoV-2 pneumonia.

Clinical Evaluation of Self-Collected Saliva by Quantitative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-Mediated Isothermal Amplification, and a Rapid Antigen Test To Diagnose COVID-19.

The clinical performances of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva. Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse transcription-PCR (RT-qPCR) laboratory-developed test (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse transcription-loop-mediated isothermal amplification (RT-LAMP). The viral antigen was detected by a rapid antigen immunochromatographic assay. Of the 103 samples, viral RNA was detected in 50.5 to 81.6% of the specimens by molecular diagnostic tests, and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at significantly higher percentages (65.6 to 93.4%) in specimens collected within 9 days of symptom onset than in specimens collected after at least 10 days of symptoms (22.2 to 66.7%) and in specimens collected from asymptomatic patients (40.0 to 66.7%). Self-collected saliva is an alternative specimen option for diagnosing COVID-19. The RT-qPCR LDT, a cobas SARS-CoV-2 high-throughput system, direct RT-qPCR kits (except for one commercial kit), and RT-LAMP showed sufficient sensitivities in clinical use to be selectively used in clinical settings and facilities. The rapid antigen test alone is not recommended for an initial COVID-19 diagnosis because of its low sensitivity.

Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis.

BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7·25, 95% CI 1·43-36·70; p=0·020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0·028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0·035) and lymphopenia (16 [57%] vs ten [23%]; p=0·0055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.

An enterohaemorrhagic Escherichia coli outbreak spread through the environment at an institute for people with intellectual disabilities in Japan in 2005.

OBJECTIVE: An enterohaemorrhagic Escherichia coli (EHEC) outbreak at an institute with multiple facilities for children and adults with intellectual disabilities was investigated to characterize the cases and identify risk factors for infection. METHODS: A case was defined as a resident, a staff member or a visitor at the institute from 16 May through 30 June 2005 testing positive for type 2 Vero toxin-producing EHEC O157:H7 (confirmed case) or exhibiting bloody diarrhoea for two or more days (probable case). We collected and analysed demographic, clinical, laboratory and individual behaviour data to identify possible risk factors for infection and infection routes. RESULTS: We recorded 58 confirmed cases, of which 13 were symptomatic. One probable case was also found. The median age of the patients was 37 years (range: 6-59 years). Thirty-six patients (61%) were male. Thirteen patients (93%) had diarrhoea and six (43%) had abdominal pain. Two developed haemolytic-uraemic syndrome but recovered. All the patients were treated with antibiotics and tested negative after treatment. Some residents had problems with personal hygiene. The residents of one of the facilities who cleaned a particular restroom had 18.0 times higher odds of being infected with EHEC (95% confidence interval: 4.0-102.4) than those who did not. DISCUSSION: The source of the outbreak could not be identified; however, the infection may have spread through environmental sources contaminated with EHEC. We recommend that institutional settings, particularly those that accommodate people with intellectual disabilities, clean restrooms as often as possible to reduce possible infection from contact with infected surfaces.

Analysis of influenza transmission in the households of primary and junior high school students during the 2012-13 influenza season in Odate, Japan.

BACKGROUND: Households are one of the major settings of influenza transmission in the community and transmission is frequently initiated by school-aged children. We surveyed households with primary school (PS) and/ or junior high school (JH) children for the 2012-13 influenza season in Odate, Japan then characterized the epidemiology of influenza household transmission as well as estimated the serial intervals. METHODS: We delivered a self-reported questionnaire survey to households with PS and/or JH school children in Odate City, Japan. Influenza A (H3N2) virus predominantly circulated during the 2012-13 influenza season. We investigated the epidemiological characteristics of within-household transmission and calculated the serial intervals (SI). SIs were drew by a non-parametric model and compared with parametric models by the Akaike Information Criterion. The covariable contributions were investigated by the accelerated failure model. RESULTS: Household influenza transmission was identified in 255 out of 363 household respondents. Primary school (PS) children accounted for 45.1 % of primary cases, and disease transmission was most commonly observed between PS children and parents, followed by transmission from PS children to siblings. In primary cases of PS or JH children, younger age and longer absence from school were significantly associated with household transmission events. The mean SI was estimated as 2.8 days (95 % confidence interval 2.6-3.0 days) in the lognormal model. The estimated acceleration factors revealed that while secondary school age and the absence duration > 7 days were associated with shorter and longer SIs, respectively, antiviral prescriptions for primary cases made no contribution. CONCLUSIONS: High frequencies of household transmission from primary school with shorter SI were found. These findings contribute to the development of future mitigation strategies against influenza transmission in Japan.

Role of Preschool and Primary School Children in Epidemics of Influenza A in a Local Community in Japan during Two Consecutive Seasons with A(H3N2) as a Predominant Subtype.

Enhanced influenza surveillance was implemented to analyze transmission dynamics particularly driving force of influenza transmission in a community during 2011/12 and 2012/13 seasons in Odate City, Japan. In these two consecutive seasons, influenza A(H3N2) was the predominant influenza A subtype. Suspected influenza cases were tested by commercial rapid test kits. Demographic and epidemiological information of influenza positive cases were recorded using a standardized questionnaire, which included age or age group, date of visit, date of fever onset, and the result of rapid test kit. Epidemiological parameters including epidemic midpoint (EM) and growth rate (GR) were analyzed. In 2012/13 season, numbers of influenza A positive cases were significantly lower among preschool (212 cases) and primary school (224 cases) children than in 2011/12 season (461 and 538 cases, respectively). Simultaneously, total influenza A cases were also reduced from 2,092 in 2011/12 season to 1,846 in 2012/13 season. The EMs in preschool and primary school children were earlier than EMs for adult and all age group in both 2011/12 and 2012/13 seasons. The GR in 2012/13 season was significantly lower than that in 2011/12 season (0.11 and 0.18, respectively, p = 0.003). Multiple linear regression analysis by school districts revealed that GRs in both seasons were significantly correlated with the incidence of school age children. Our findings suggest that preschool and primary school children played an important role as a driving force of epidemics in the community in both 2011/12 and 2012/13 seasons. The reduction of total influenza A cases in 2012/13 season can be explained by decreased susceptible population in these age groups due to immunity acquired by infections in 2011/12 season. Further investigations are needed to investigate the effect of pre-existing immunity on influenza transmission in the community.

Analysis of medical consultation interval between the symptom onset and consultation observed in multiple medical facilities in Odate city, Japan, 2011/2012 and 2012/2013 seasons.

BACKGROUND: Influenza remains one of the most important causes of respiratory infection despite the widespread availability of vaccines. Anti-influenza viral agents such as neuraminidase inhibitors are generally efficacious in alleviating the symptoms if they are administered within 2 days of the illness onset. However, few studies have examined the situation of interval between illness onset and medical consultation in influenza outpatients on community level. And the predictors or determinants for longer medical consultation interval have not been well-defined. MATERIAL AND METHOD: An enhanced surveillance study was conducted in Odate city of Japan in 2 consecutive seasons from 2011 to 2013. The late consultation rate (>2 days) and its risk factors were investigated in confirmed influenza outpatients. RESULTS: A proportion of 5.5% of patients visited doctors beyond 2 days of illness onset. Illness onset during non-high-incidence period, infection with influenza B and being adult or elderly were identified as independent risk factors for late consultation and the risk increased with the number of risk factors. CONCLUSION: The consultation behavior for influenza was generally well in our study population. Identified risk factors should be addressed in health education and promotion for the late consultation.

Tuberculosis contact investigation using interferon-gamma release assay with chest x-ray and computed tomography.

Between September 2009 and January 2010, 6 members of the Japanese Eastern Army, who had completed the same training program, were diagnosed with active tuberculosis (TB) on different occasions. The Ministry of Defense conducted a contact investigation of all members who had come into contact with the infected members. The purpose of this study was to verify the efficacy of the TB screening protocol used in this investigation. A total of 884 subjects underwent interferon-gamma release assay (IGRA) and chest X-ray. The 132 subjects who were IGRA positive or with X-ray findings suggestive of TB subsequently underwent chest computer tomography (CT). Chest CT was performed for 132 subjects. Based on CT findings, 24 (2.7%) subjects were classified into the active TB group, 107 (12.1%) into the latent tuberculosis infection (LTBI) group, and 753 (85.2%) into the non-TB group. The first 2 groups underwent anti-TB therapy, and all 3 groups were followed for 2 years after treatment. Although one subject in the active TB group experienced relapse during the follow-up period, no patient in the LTBI or non-TB groups developed TB. IGRA and chest X-ray, followed by chest CT for those IGRA positive or with suspicious X-ray findings, appears to be an effective means of TB contact screening and infection prevention.

[Infectious disease surveillance in Miyagi after the Great East Japan Earthquake].

OBJECTIVES: The Great East Japan Earthquake, which occurred on March 11, 2011, damaged many health facilities and compelled many inhabitants to live in evacuation centers. For the purpose of monitoring infectious disease outbreaks, infectious disease surveillance targeted at evacuation centers was established in Miyagi Prefecture. In this study, we summarized the monitoring activities of infectious diseases through this surveillance after the earthquake. METHODS: Infectious disease surveillance was implemented from March 18 to November 6, 2011. The surveillance consisted of two phases (hereafter, surveillance 1 and 2) reflecting the difference in frequencies of reporting as well as the number of targeted diseases. Surveillance 1 operated between March 18 and May 13, 2011, and Surveillance 2 operated between May 10 and November 6, 2011. We reviewed the number of cases reported, the number of evacuation centers, and demographic information of evacuees with the surveillance. RESULTS: In Surveillance 1, there were 8,737 reported cases; 84% of them were acute respiratory symptoms, and 16% were acute digestive symptoms. Only 4.4% of evacuation centers were covered by the surveillance one week after the earthquake. In Surveillance 2, 1,339 cases were reported; 82% of them were acute respiratory symptoms, and 13% were acute digestive symptoms. Surveillance 2 revealed that the proportion of children aged 5 years and younger was lower than that of other age groups in all targeted diseases. No particular outbreaks were detected through those surveillances. CONCLUSION: Infectious disease surveillance operated from one week after the earthquake to the closure of all evacuation centers in Miyagi Prefecture. No outbreaks were detected in that period. However, low coverage of evacuation centers just after the earthquake as well as skewed frequencies of reported syndromes draw attention to the improvement of the early warning system. It is important to coordinate with the medical aid team that visits the evacuation centers on a regular basis and to obtain information about the characteristics of evacuees. It is necessary to establish a surveillance system that can monitor infectious disease efficiently from an early phase.

Mobile and accurate detection system for infection by the 2009 pandemic influenza A (H1N1) virus with a pocket-warmer reverse-transcriptase loop-mediated isothermal amplification.

The 2009 pandemic H1N1 influenza A virus spread quickly worldwide in 2009. Since most of the fatal cases were reported in developing countries, rapid and accurate diagnosis methods that are usable in poorly equipped laboratories are necessary. In this study, a mobile detection system for the 2009 H1N1 influenza A virus was developed using a reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) kit with a disposable pocket-warmer as a heating device (designated as pwRT-LAMP). The pwRT-LAMP can detect as few as 100 copies of the virus--which is nearly as sensitive as real-time reverse-transcription polymerase chain reaction (RT-PCR)--and does not cross-react with RNA of seasonal influenza viruses. To evaluate the usefulness of the pwRT-LAMP system, nasal swab samples were collected from 56 patients with flu-like symptoms and were tested. Real-time RT-PCR confirmed that the 2009 H1N1 influenza A virus was present in 27 of the 56 samples. Of these 27 positive samples, QuickVue Influenza A+B immunochromatography detected the virus in only 11 samples (11/27; 40.7%), whereas the pwRT-LAMP system detected the virus in 26 of the 56 samples (26/27 of the positive samples; 96.3%). These findings indicate that the mobile pwRT-LAMP system is an accurate diagnostic system for the 2009 H1N1 influenza A virus, and has great potential utility in diagnosing future influenza pandemics.

Paget-Schroetter syndrome and pulmonary thromboembolism: clinical follow-up over 5 years.

A scaffold constructor lost consciousness at work, leading to emergency admission to our hospital. He had noted gradual worsening of exertional dyspnea over the previous 1 month. Chest radiography showed localized oligemia and enlarged hilar vessels. Pulmonary perfusion scintigraphy confirmed the existence of multiple perfusion defects, so a diagnosis of pulmonary thromboembolism was made. Upper and lower limb venography disclosed interruption of the right subclavian vein (so-called Paget-Schroetter syndrome). However, there was no difference in appearance between the right and left upper extremities. Five years after starting anticoagulant therapy, his symptoms have resolved, but serial perfusion scintigraphy and upper extremity venography revealed the persistence of abnormalities. In patients with pulmonary thromboembolism, lifestyle factors (especially heavy manual labor) should be considered and the possibility of subclavian vein thrombosis should be kept in mind.

A case report of congenital isolated absence of the right pulmonary artery: bronchofibrescopic findings and chest radiological tracings over 9 years.

A 27-year-old man was admitted to hospital for investigation of haemoptysis. He was a serving member of the Japan Self-Defense Forces. A CXR showed absence of the right hilum, and the right hemithorax was smaller than the contralateral hemithorax. Pulmonary arteriography demonstrated complete absence of the right pulmonary artery. Right heart catheterisation did not show any concomitant cardiovascular malformations, and the patient was diagnosed as having isolated absence of the right pulmonary artery. Bronchial arteriograms demonstrated enlargement and proliferation of the small branches of the right bronchial artery. Bronchofibrescopic examination showed obvious enlargement of the bronchial mucosal vessels with submucosal eruptions and swelling in the right bronchial tree, but not on the left side. Re-examination of the patient's CXR from the previous 9 years revealed a chronological decrease of right lung volume and an increase of the cardiothoracic ratio. Isolated absence of the right pulmonary artery is generally considered to have a good prognosis, but close observation is necessary to monitor the pulmonary haemodynamics.

[Pulmonary thromboembolism complicating right subclavian vein obstruction: case report].

We report a case of pulmonary thromboembolism, in which obstruction of the right subclavian vein, also called Paget-von Schroetter syndrome, was detected. The patient was a 39-year-old man (a scaffold constructor). He lost consciousness at work, and was admitted as an emergency case to our hospital. He had noticed gradually worsening dyspnea for 1 month. Chest radiography showed Westmark's sign in the lungs and enlarged hilar vascular markings on both sides. Pulmonary perfusion scintigraphy confirmed multiple flow defects. Upper and lower limb venography disclosed interruption of the right subclavian vein, leading to a diagnosis of pulmonary thromboembolism secondary to upper limb vein thrombosis. In patients who have pulmonary thromboembolism without an apparent underlying disease, the lifestyle and work habits should be considered and the possibility of subclavian vein thrombosis should be kept in mind.

[A case report of isolated absence of the right pulmonary artery: bronchofiberscopic findings and chest radiologic tracings over 9 years].

A 27-year-old man was admitted to hospital for the investigation of hemosputum. He is a serving member of the Japan Self-Defense Forces. Chest radiography showed absence of the right hilar component, and the ipsilateral hemithorax was smaller than that of on the left side. Pulmonary arteriography demonstrated complete absence of the right pulmonary artery. Right cardiac catheterization did not show any concomitant cardio-vascular malformation. Therefore, this case was diagnosed as an isolated absence of the right pulmonary artery. Bronchial arteriograms demonstrated showed vascular enlargement and proliferation of the right bronchial artery. Bronchofiberscopic examination showed obvious bronchial mucosal vascular enlargement with submucosal eruption and swelling of the right bronchi. We also re-examined the chest radiographs of this patient from the previous 9-years. Those revealed a chronological decrease of the right lung volume and an increase of the cardio-thoracic ratio. Isolated absence of the right pulmonary artery is generally considered to have preferable survival, but close observation is necessary to monitor the pulmonary hemodynamics.

[Summer-type hypersensitivity pneumonitis in monozygotic twins].

We encountered a pair of monozygotic twins with summer-type hypersensitivity pneumonitis. Patients 1 and 2 were 24-year-old men who worked in the same place and shared the same room, which was built of wood. In August, patient 1, a non-smoker, was referred to our hospital because of coughing, fever and dyspnea. In November, the same symptoms appeared in patient 2, who was a smoker. The difference between the onset times in patients 1 and 2 was suspected to be due to cigarette smoking, because their occupations and other circumstances were the same and they were monozygotic twins.

[Pulmonary involvement in sarcoidosis: CT findings at diagnosis and their changes at follow-up in cases without corticosteroid treatment].

To review the pulmonary CT findings in sarcoidosis at diagnosis, and to analyze the change in each finding at follow-up in cases without corticosteroid treatment. The study included 21 cases of pulmonary involvement of sarcoidosis. We analyzed the presence or absence and grade of each HRCT finding: bronchial wall thickening, enlargement of vascular shadows, pleural involvement, septal thickening, small nodules, ground-glass opacities, centrilobular opacities, consolidation, nodules, and volume loss. Afterwards, we compared the initial CT with the follow-up CT, and described the change of each finding as "improved" or "not improved". Furthermore, we decided if each case as a whole was improved or not after considering all of the pulmonary CT findings. Twelve of the 21 cases were improved. Small nodules, ground-glass opacities, centrilobular opacities, and nodules had improved in more than 50% of the cases since the initial CT. However, pleural involvement (10/11) and volume loss (6/9) were not improved. Pleural involvement and volume loss correlated the radiological irreversibility (p < 0.05). Of the several pulmonary CT findings in sarcoidosis, pleural involvement and volume loss show the highest rates of irreversible pulmonary changes.

A transcriptional activator, AoXlnR, controls the expression of genes encoding xylanolytic enzymes in Aspergillus oryzae.

By deletion across the promoter region of the xynF1 gene encoding the major Aspergillus oryzae xylanase, a 53-bp DNA fragment containing the XlnR binding sequence GGCTAAA as well as two similar sequences was shown to confer xylan inducibility on the gene. Complementary and genomic DNAs encoding the Aspergillus niger xlnR homologous gene, abbreviated AoxlnR, were cloned from A. oryzae and sequenced. AoXlnR comprised 971 amino acids with a zinc binuclear cluster domain at the N-terminal region and revealed 77.5% identity to the A. niger XlnR. Recombinant AoXlnR protein encompassing the zinc cluster region of the N-terminal part bound to both the consensus binding sequence and its cognate sequence, GGCTGA, with an approximately 10 times lower affinity. GGCTA/GA is more appropriate as the XlnR consensus binding sequence. Both sequences functioned independently in vivo in XlnR-mediating induction of the xynF1 gene. This was further confirmed by using an AoxlnR disruptant. Neither the xynF1 nor the xylA gene was expressed in the disruptant, suggesting that the xylan-inducible genes in A. oryzae may also be controlled in the same manner as described for A. niger.