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Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.
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COVID-19 , Humanos , SARS-CoV-2 , Esparcimiento de Virus , Formación de Anticuerpos , Tiempo de Reacción , Anticuerpos Antivirales , ARN Viral , Inmunoglobulina G , Inmunoglobulina A , Inmunoglobulina A SecretoraRESUMEN
Rapid diagnostic tests (RDTs) significantly impact disease treatment strategy. In Japan, information on the use of RDTs for patients with COVID-19 is limited. Here, we aimed to investigate the RDT implementation rate, pathogen detection rate, and clinical characteristics of patients positive for other pathogens by using COVIREGI-JP, a national registry of hospitalized patients with COVID-19. A total of 42,309 COVID-19 patients were included. For immunochromatographic testing, influenza was the most common (n = 2881 [6.8%]), followed by Mycoplasma pneumoniae (n = 2129 [5%]) and group A streptococcus (GAS) (n = 372 [0.9%]). Urine antigen testing was performed for 5524 (13.1%) patients for S. pneumoniae and for 5326 patients (12.6%) for L. pneumophila. The completion rate of M. pneumonia loop-mediated isothermal amplification (LAMP) testing was low (n = 97 [0.2%]). FilmArray RP was performed in 372 (0.9%) patients; 1.2% (36/2881) of patients were positive for influenza, 0.9% (2/223) for the respiratory syncytial virus (RSV), 9.6% (205/2129) for M. pneumoniae, and 7.3% (27/372) for GAS. The positivity rate for urine antigen testing was 3.3% (183/5524) for S. pneumoniae and 0.2% (13/5326) for L. pneumophila. The positivity rate for LAMP test was 5.2% (5/97) for M. pneumoniae. Five of 372 patients (1.3%) had positive FilmArray RP, with human enterovirus being the most frequently detected (1.3%, 5/372). The characteristics of patients with and without RDTs submission and positive and negative results differed for each pathogen. RDTs remain an important diagnostic tool in patients with COVID-19 in whom coinfection with other pathogens needs to be tested based on clinical evaluation.
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COVID-19 , Gripe Humana , Virus Sincitial Respiratorio Humano , Humanos , COVID-19/diagnóstico , Gripe Humana/diagnóstico , Prueba de Diagnóstico Rápido , Mycoplasma pneumoniae/genética , Prueba de COVID-19RESUMEN
To determine virus shedding duration, we examined clinical samples collected from the upper respiratory tracts of persons infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in Japan during November 29-December 18, 2021. Vaccinees with mild or asymptomatic infection shed infectious virus 6-9 days after onset or diagnosis, even after symptom resolution.
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COVID-19 , Enfermedades Transmisibles , Infecciones Asintomáticas , Humanos , SARS-CoV-2 , Esparcimiento de VirusRESUMEN
INTRODUCTION: The post-COVID condition has become a social concern. Although the patient characteristics associated with the development of this condition are partially known, those associated with its persistence have not been identified. METHODS: We conducted a cross-sectional questionnaire-based survey among patients who had recovered from COVID-19 and visited the National Center for Global Health and Medicine between February 2021 and March 2021. Demographic and clinical data, and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the development and persistence of post-COVID conditions using multivariate logistic and linear regression analyses, respectively. RESULTS: We analyzed 457 of 526 responses (response rate, 86.9%). The median patient age was 47 years. Of these, 378 patients (84.4%) had mild disease in the acute phase. The number of patients with symptoms at 6 and 12 months after onset or diagnosis was 120 (26.3%) and 40 (8.8%), respectively. Women were at risk of developing fatigue (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.31-3.14), dysosmia (OR: 1.91, 95%CI: 1.24-2.93), dysgeusia (OR: 1.56, 95%CI: 1.02-2.39), hair loss (OR: 3.00, 95%CI: 1.77-5.09), and persistence of any symptoms (coefficient: 38.0, 95%CI: 13.3-62.8). Younger age and low body mass index were factors for developing dysosmia (OR: 0.96, 95%CI: 0.94-0.98 and OR: 0.94, 95%CI: 0.89-0.99, respectively) and dysgeusia (OR: 0.98, 95%CI: 0.96-1.00 and OR: 0.93, 95%CI: 0.88-0.98, respectively). CONCLUSION: We identified factors involved in the development and persistence of post-COVID conditions. Many patients, even those with mild conditions, experience long-term residual symptoms.
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COVID-19 , Trastornos del Olfato , COVID-19/epidemiología , Estudios Transversales , Disgeusia/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Trastornos del Olfato/diagnóstico , SARS-CoV-2RESUMEN
BACKGROUND: There is limited understanding of the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan. METHODS: This study included 2638 cases enrolled from 227 healthcare facilities that participated in the COVID-19 Registry Japan (COVIREGI-JP). The inclusion criteria for enrollment of a case in COVIREGI-JP are both (1) a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and (2) inpatient treatment at a healthcare facility. RESULTS: The median age of hospitalized patients with COVID-19 was 56 years (interquartile range [IQR], 40-71 years). More than half of cases were male (58.9%, 1542/2619). Nearly 60% of the cases had close contact to confirmed or suspected cases of COVID-19. The median duration of symptoms before admission was 7 days (IQR, 4-10 days). The most common comorbidities were hypertension (15%, 396/2638) and diabetes without complications (14.2%, 374/2638). The number of nonsevere cases (68.2%, nâ =â 1798) was twice the number of severe cases (31.8%, nâ =â 840) at admission. The respiratory support during hospitalization includes those who received no oxygen support (61.6%, 1623/2636) followed by those who received supplemental oxygen (29.9%, 788/2636) and invasive mechanical ventilation/extracorporeal membrane oxygenation (8.5%, 225/2636). Overall, 66.9% (1762/2634) of patients were discharged home, while 7.5% (197/2634) died. CONCLUSIONS: We identified the clinical epidemiological features of COVID-19 in hospitalized patients in Japan. When compared with existing inpatient studies in other countries, these results demonstrated fewer comorbidities and a trend towards lower mortality.
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COVID-19 , Adulto , Anciano , Hospitalización , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros , SARS-CoV-2RESUMEN
INTRODUCTION: The automated quantitative antigen test (QAT), which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is suitable for mass screening. However, its diagnostic capability differentiated by time from onset and potential contribution to infectivity assessment have not been fully investigated. METHODS: A retrospective, observational study using nasopharyngeal swab specimens from coronavirus disease (COVID-19) inpatients was conducted using Lumipulseâ SARS-CoV-2 antigen test. Diagnostic accuracy was examined for the early (up to 10 days after onset) and late (over 10 days after onset) stages. Time-course QAT changes and reverse-transcription quantitative polymerase chain reaction tests results were displayed as locally estimated scatterplot smoothing curve, and receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cutoff value for differentiating the early and late stages. RESULTS: We obtained 100 specimens from 68 COVID-19 patients, including 51 early-stage and 49 late-stage specimens. QAT sensitivity and specificity were 0.82 (0.72-0.90) and 0.95 (0.75-0.99) for all periods, 0.93 (0.82-0.98) and 1.00 (0.39-1.00) for the early stage, and 0.66 (0.48-0.82) and 0.93 (0.69-0.99) for the late stage, respectively. The ROC analysis indicated an ideal cutoff value of 6.93 pg/mL for distinguishing early-from late-stage specimens. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting the late stage were 0.76 (0.61-0.87), 0.76 (0.63-0.87), 0.76 (0.61-0.87), and 0.76 (0.63-0.87). CONCLUSIONS: QAT has favorable diagnostic accuracy in the early COVID-19 stages. In addition, an appropriate cutoff point can potentially facilitate rapid identification of noncontagious patients.
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COVID-19 , SARS-CoV-2 , Humanos , Pruebas Inmunológicas , Nasofaringe , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Most of the currently used prognostic models for COVID-19 are based on Western cohorts, but it is unknown whether any are applicable to patients with COVID-19 in Japan. METHODS: This retrospective cohort study included 160 patients with COVID-19 who were admitted to the National Center for Global Health and Medicine between January 26, 2020 and July 25, 2020. We searched PubMed for prognostic models for COVID-19. The predicted outcome was initiation of respiratory support or death. Performance of the candidate models was evaluated according to discrimination and calibration. We recalibrated the intercept of each model with our data. We also updated each model by adding ß2-microglobulin (ß2MG) to the model and recalculating the intercept and the coefficient of ß2MG. RESULTS: Mean patient age was 49.8 years, 68% were male, 88.7% were Japanese. The study outcomes occurred in 15 patients, including two deaths. Two-hundred sixty-nine papers were screened, and four candidate prognostic models were assessed. The model of Bartoletti et al. had the highest area under receiver operating characteristic curve (AUC) (0.88; 95% confidence interval 0.81-0.96). All four models overestimated the probability of occurrence of the outcome. None of the four models showed statistically significant improvement in AUCs by adding ß2MG. CONCLUSIONS: Our results suggest that the existing prediction models for COVID-19 overestimate the probability of occurrence of unfavorable outcomes in a Japanese cohort. When applying a prediction model to a different cohort, it is desirable to evaluate its performance according to the prevalent health situation in that region.
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COVID-19 , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0-6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation.
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Autofagia/efectos de la radiación , Locomoción/efectos de la radiación , Dosis de Radiación , Animales , Autofagia/fisiología , Caenorhabditis elegans/fisiología , Caenorhabditis elegans/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Humanos , Locomoción/fisiología , Irradiación Corporal Total/efectos adversosRESUMEN
Microglia remove apoptotic cells by phagocytosis when the central nervous system is injured in vertebrates. Ionizing irradiation (IR) induces apoptosis and microglial activation in embryonic midbrain of medaka (Oryzias latipes), where apolipoprotein E (ApoE) is upregulated in the later phase of activation of microglia In this study, we found that another microglial marker, l-plastin (lymphocyte cytosolic protein 1), was upregulated at the initial phase of the IR-induced phagocytosis when activated microglia changed their morphology and increased motility to migrate. We further conducted targeted irradiation to the embryonic midbrain using a collimated microbeam of carbon ions (250 µm diameter) and found that the l-plastin upregulation was induced only in the microglia located in the irradiated area. Then, the activated microglia might migrate outside of the irradiated area and spread through over the embryonic brain, expressing ApoE and with activated morphology, for longer than 3 days after the irradiation. These findings suggest that l-plastin and ApoE can be the biomarkers of the activated microglia in the initial and later phase, respectively, in the medaka embryonic brain and that the abscopal and persisted activation of microglia by IR irradiation could be a cause of the abscopal and/or adverse effects following irradiation.
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Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Iones Pesados , Microglía/metabolismo , Microglía/efectos de la radiación , Radiación Ionizante , Animales , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apoptosis/efectos de la radiación , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Embrión no Mamífero , Peces , Expresión Génica , Iones Pesados/efectos adversos , Neuronas/metabolismo , Neuronas/efectos de la radiación , OryziasRESUMEN
The global outbreak of mpox in 2022 and subsequent sporadic outbreaks in 2023 highlighted the importance of nonpharmaceutical interventions such as case isolation. Individual variations in viral shedding dynamics may lead to either premature ending of isolation for infectious individuals, or unnecessarily prolonged isolation for those who are no longer infectious. Here, we developed a modeling framework to characterize heterogeneous mpox infectiousness profiles - specifically, when infected individuals cease to be infectious - based on viral load data. We examined the potential effectiveness of three different isolation rules: a symptom-based rule (the current guideline in many countries) and rules permitting individuals to stop isolating after either a fixed duration or following tests that indicate that they are no longer likely to be infectious. Our analysis suggests that the duration of viral shedding ranges from 23 to 50 days between individuals. The risk of infected individuals ending isolation too early was estimated to be 8.8% (95% CI: 6.7-10.5) after symptom clearance and 5.4% (95% CI: 4.1-6.7) after 3 weeks of isolation. While these results suggest that the current standard practice for ending isolation is effective, we found that unnecessary isolation following the infectious period could be reduced by adopting a testing-based rule.
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Brotes de Enfermedades , Humanos , Brotes de Enfermedades/prevención & control , Carga Viral , COVID-19/epidemiología , COVID-19/virología , COVID-19/prevención & control , COVID-19/transmisión , Esparcimiento de Virus , SARS-CoV-2/aislamiento & purificación , Aislamiento de Pacientes/métodosRESUMEN
We investigated the radiation-quality-dependent bystander cellular effects using heavy-ion microbeams with different ion species. The heavy-ion microbeams were produced in Takasaki Ion Accelerators for Advanced Radiation Application, National Institutes for Quantum Science and Technology. Carbon (12C5+, 220 MeV), neon (20Ne7+, 260 MeV) and argon (40Ar13+, 460 MeV) ions were used as the microbeams, collimating the beam size with a diameter of 20 µm. After 0.5 and 3 h of irradiation, the surviving fractions (SFs) are significantly lower in cells irradiated with carbon ions without a gap-junction inhibitor than those irradiated with the inhibitor. However, the same SFs with no cell killing were found with and without the inhibitor at 24 h. Conversely, no cell-killing effect was observed in argon-ion-irradiated cells at 0.5 and 3 h; however, significantly low SFs were found at 24 h with and without the inhibitor, and the effect was suppressed using vitamin C and not dimethyl sulfoxide. The mutation frequency (MF) in cells irradiated with carbon ions was 8- to 6-fold higher than that in the unirradiated control at 0.5 and 3 h; however, no mutation was observed in cells treated with the gap-junction inhibitor. At 24 h, the MFs induced by each ion source were 3- to 5-fold higher and the same with and without the inhibitor. These findings suggest that the bystander cellular effects depend on the biological endpoints, ion species and time after microbeam irradiations with different pathways.
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Academias e Institutos , Apoptosis , Argón , Ácido Ascórbico , CarbonoRESUMEN
The functions of organisms are performed by various tissues composed of different cell types. Localized irradiation with heavy-ion microbeams, which inactivate only a portion of the constituent cells without destroying the physical intercellular connections of the tissue, is a practical approach for elucidating tissue functions. However, conventional collimated microbeams are limited in the shape of the area that can be irradiated. Therefore, using a focused heavy-ion microbeam that generates a highly precise beam spot, we developed a technology to uniformly irradiate specific tissues of an organism with a defined dose, which conventional methods cannot achieve. The performance of the developed paint irradiation technology was evaluated. By irradiating the CR-39 ion track detector, we confirmed that the new method, in which each ion hit position is placed uniformly in the irradiated area, makes it possible to uniformly paint the area at a specified dose. The targeted irradiation of the pharynx and gonads of living Caenorhabditis elegans demonstrated that the irradiated ions were distributed in the same shape as the targeted tissue observed under a microscope. This technology will elucidate biological mechanisms that are difficult to analyze with conventional collimated microbeam irradiation.
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PURPOSE: Hematopoietic tissues of vertebrates are highly radiation sensitive and the effects of ionizing radiation on the hematopoiesis have been studied in mammals and teleosts for decades. In this study, radiation responses in the kidney, the main hematopoietic organ in teleosts, were investigated in Japanese medaka (Oryzias latipes), which has been a model animal and a large body of knowledge has been accumulated in radiation biology. METHODS: Kidney, the main hematopoietic tissue of adult medaka fish, was locally irradiated using proton and carbon ion beams irradiation system of Takasaki Ion Accelerator for Advanced Radiation Application (TIARA), QST, and the effects on peripheral blood cells and histology of the kidney were investigated. RESULTS: When only kidneys were locally irradiated with proton or carbon ion beam (15 Gy), the hematopoietic cells in the irradiated kidney and cell density in the peripheral blood decreased 7 days after the irradiation in the same manner as after the whole-body irradiation with γ-rays (15 Gy). These results demonstrate that direct irradiation of the hematopoietic cells in the kidney induced cell death and/or cell cycle arrest and stopped the supply of erythroid cells. Then, the cell density in the peripheral blood recovered to the control level within 4 days and 7 days after the γ-ray and proton beam irradiation (15 Gy), respectively, while the cell density in the peripheral blood did not recover after the carbon ion beam irradiation (15 Gy). The hematopoietic cells in the irradiated kidneys temporarily decreased and recovered to the control level within 21 days after the γ-ray or proton beam irradiation (15 Gy), while it did not recover after the carbon ion beam irradiation (15 Gy). In contrast, the recovery of the cell density in the peripheral blood delayed when anemic medaka were irradiated 1 day after the administration of phenylhydrazine. With and without γ-ray irradiation, a large number of hematopoietic cells was still proliferating in the kidney 7 days after the anemia induction. CONCLUSIONS: The results obtained strongly suggest that the hematopoietic stem cells in medaka kidney prioritize to proliferate and increase peripheral blood cells to eliminate anemia, even when they are damaged by high-dose irradiation.
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Anemia , Oryzias , Animales , Oryzias/metabolismo , Protones , Rayos gamma/efectos adversos , Células Madre Hematopoyéticas , MamíferosRESUMEN
Although biomarkers to predict coronavirus disease 2019 (COVID-19) severity have been studied since the early pandemic, no clear guidelines on using them in clinical practice are available. Here, we examined the ability of four biomarkers to predict disease severity using conserved sera from COVID-19 patients who received inpatient care between January 1, 2020 and September 21, 2021 at the National Center for Global Health and Medicine, collected at the appropriate time for prediction. We predicted illness severity in two situations: 1) prediction of future oxygen administration for patients without oxygen support within 8 days of onset (Study 1) and 2) prediction of future mechanical ventilation support (excluding non-invasive positive pressure ventilation) or death of patients within 4 days of the start of oxygen administration (Study 2). Interleukin-6, IFN-λ3, thymus and activation-regulated chemokine, and calprotectin were measured retrospectively. Other laboratory and clinical information were collected from medical records. AUCs were calculated from ROC curves and compared for the predictive ability of the four biomarkers. Study 1 included 18 patients, five of whom had developed oxygen needs. Study 2 included 45 patients, 13 of whom required ventilator management or died. In Study 1, IFN-λ3 showed a good predictive ability with an AUC of 0.92 (95% CI 0.76-1.00). In Study 2, the AUC of each biomarker was 0.70-0.74. The number of biomarkers above the cutoff showed the possibility of good prediction with an AUC of 0.86 (95% CI 0.75-0.97). When two or more biomarkers were positive, sensitivity and specificity were 0.92 and 0.63, respectively. In terms of biomarker testing at times when prognostication may be clinically useful, IFN-λ3 was predictive of oxygenation demand and a combination of the four biomarkers was predictive of mechanical ventilator requirement.
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COVID-19 , Humanos , Biomarcadores , Quimiocina CCL17 , COVID-19/diagnóstico , Interleucina-6 , Complejo de Antígeno L1 de Leucocito , Oxígeno , Pronóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
A neural oscillator with a double-chain structure is one of the central pattern generator models used to simulate and understand rhythmic movements in living organisms. However, it is difficult to reproduce desired rhythmic signals by tuning an enormous number of parameters of neural oscillators. In this study, we propose an automatic tuning method consisting of two parts. The first involves tuning rules for both the time constants and the amplitude of the oscillatory outputs based on theoretical analyses of the relationship between parameters and outputs of the neural oscillators. The second involves an evolutionary tuning method with a two-step genetic algorithm (GA), consisting of a global GA and a local GA, for tuning parameters such as neural connection weights that have no exact tuning rule. Using numerical experiments, we confirmed that the proposed tuning method could successfully tune all parameters and generate sinusoidal waves. The tuning performance of the proposed method was less affected by factors such as the number of excitatory oscillators or the desired outputs. Furthermore, the proposed method was applied to the parameter-tuning problem of some types of artificial and biological wave reproduction and yielded optimal parameter values that generated complex rhythmic signals in Caenorhabditis elegans without trial and error.
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Algoritmos , Relojes Biológicos/fisiología , Modelos Neurológicos , Animales , Caenorhabditis elegansRESUMEN
Chemotaxis in the nematode Caenorhabditis elegans has basically been examined using conventional assay methods. Although these can be problematic, for example, in their use of anesthesia, the method has never been improved. We propose a pond assay for the sensory systems (PASS) of C. elegans as a novel population-based method of behavioral analysis. The test solution is injected into a recess(es) formed on agar and the response of C. elegans to its odor and/or taste is examined. Once C. elegans individuals fall into recesses (ponds) filled with liquid, they cannot return to a solid medium. In this way, the animals are trapped with certainty without the use of anesthesia. The anesthesia used to keep animals in the attractant area in conventional chemotaxis assays is no longer required, allowing pure evaluation of the attractant or repellent response to specific substances. Furthermore, the assay itself can be greatly streamlined because the preparation can be completed simply by providing a recess(es) and filling the liquid. The present paper reports the detailed method and effectiveness of the novel PASS.
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The nematode Caenorhabditis elegans is a powerful experimental model to investigate vital functions of higher organisms. We recently established a novel method, named "pond assay for the sensory systems (PASS)", that dramatically improves both the evaluation accuracy of sensory response of worms and the efficiency of experiments. This method uses many worms in numbers that are impractical to count manually. Although several automated detection systems have been introduced, detection of overlapped worms remains difficult. To overcome this problem, we developed an automated worm detection system based on a deep neural network (DNN). Our DNN was based on a "YOLOv4â³ one-stage detector with one-class classification (OCC) and multi-class classification (MCC). The OCC defined a single class for worms, while the MCC defined four classes for the number of overlapped worms. For the training data, a total of 2000 model sub-images were prepared by manually drawing square worm bounding boxes from 150 images. To make simulated images, a total of 10-80 model images for each class were randomly selected and randomly placed on a simulated microscope field. A total of 19,000 training datasets and 1000 validation datasets with a ground-truth bounding-box were prepared. We evaluated detection accuracy using 150 images, which were different from the training data. Evaluation metrics were detection error, precision, recall, and average precision (AP). Precision values were 0.91 for both OCC and MCC. However, the recall value for MCC (= 0.93) was higher than that for OCC (= 0.79). The number of detection errors for OCC increased with increasing the ground truth; however, that for MCC was independent of the ground truth. AP values were 0.78 and 0.90 for the OCC and the MCC, respectively. Our worm detection system with MCC provided better detection accuracy for large numbers of worms with overlapping positions than that with the OCC.
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Redes Neurales de la ComputaciónRESUMEN
The outbreak of COVID-19 caused by infection with SARS-CoV-2 virus has become a worldwide pandemic, and the number of patients presenting with respiratory failure is rapidly increasing in Japan. An international meta-analysis has been conducted to identify genetic factors associated with the onset and severity of COVID-19, but these factors have yet to be fully clarified. Here, we carried out genomic analysis based on a genome-wide association study (GWAS) in Japanese COVID-19 patients to determine whether genetic factors reported to be associated with the onset or severity of COVID-19 in the international meta-GWAS are replicated in the Japanese population, and whether new genetic factors exist. Although no significant genome-wide association was detected in the Japanese GWAS, an integrated analysis with the international meta-GWAS identified for the first time the involvement of the IL17A/IL17F gene in the severity of COVID-19. Among nine genes reported in the international meta-GWAS as genes involved in the onset of COVID-19, the association of FOXP4-AS1, ABO, and IFNAR2 genes was replicated in the Japanese population. Moreover, combined analysis of ABO and FUT2 genotypes revealed that the presence of oral AB antigens was significantly associated with the onset of COVID-19. FOXP4-AS1 and IFNAR2 were also significantly associated in the integrated analysis of the Japanese GWAS and international meta-GWAS when compared with severe COVID-19 cases and the general population. This made it clear that these two genes were also involved in not only the onset but also the severity of COVID-19. In particular, FOXP4-AS1 was not found to be associated with the severity of COVID-19 in the international meta-GWAS, but an integrated analysis with the Japanese GWAS revealed an association with severity. Individuals with the SNP risk allele found between IL17A and IL17F had significantly lower mRNA expression levels of IL17F, suggesting that activation of the innate immune response by IL17F may play an important role in the severity of SARS-CoV-2 infection.
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Sistema del Grupo Sanguíneo ABO/genética , COVID-19/patología , Interleucina-17/genética , Saliva/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Alelos , COVID-19/genética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Japón , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The detection of other pathogens in patients with hospitalized coronavirus disease (COVID-19) are not frequent. Considering that data from Japan are limited, we conducted an observational study including patients with hospitalized COVID-19 at the National Center for Global Health and Medicine from January to September 2020. In total, 247 patients with COVID-19 were included in the study. Rapid diagnostic tests, such as immunochromatography, were performed in 31 patients (12.6%). The Film Array Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2. Respiratory bacterial culture was performed in 66 (26.7%) patients, with gram-positive bacteria, gram-negative bacteria and normal flora being detected in eight (12.1%), seven (10.6%), and 63 (95.5%) patients, respectively. Patients for whom cultures were performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was performed more frequently in the early than in the later period of the epidemic, without any differences being observed in bacterial detection rates. The proportion of viral and bacterial detection among hospitalized patients with COVID-19 in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effect of each pathogen on the clinical course of COVID-19.