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1.
Med Image Anal ; 70: 101992, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33601166

RESUMO

The recent outbreak of Coronavirus Disease 2019 (COVID-19) has led to urgent needs for reliable diagnosis and management of SARS-CoV-2 infection. The current guideline is using RT-PCR for testing. As a complimentary tool with diagnostic imaging, chest Computed Tomography (CT) has been shown to be able to reveal visual patterns characteristic for COVID-19, which has definite value at several stages during the disease course. To facilitate CT analysis, recent efforts have focused on computer-aided characterization and diagnosis with chest CT scan, which has shown promising results. However, domain shift of data across clinical data centers poses a serious challenge when deploying learning-based models. A common way to alleviate this issue is to fine-tune the model locally with the target domains local data and annotations. Unfortunately, the availability and quality of local annotations usually varies due to heterogeneity in equipment and distribution of medical resources across the globe. This impact may be pronounced in the detection of COVID-19, since the relevant patterns vary in size, shape, and texture. In this work, we attempt to find a solution for this challenge via federated and semi-supervised learning. A multi-national database consisting of 1704 scans from three countries is adopted to study the performance gap, when training a model with one dataset and applying it to another. Expert radiologists manually delineated 945 scans for COVID-19 findings. In handling the variability in both the data and annotations, a novel federated semi-supervised learning technique is proposed to fully utilize all available data (with or without annotations). Federated learning avoids the need for sensitive data-sharing, which makes it favorable for institutions and nations with strict regulatory policy on data privacy. Moreover, semi-supervision potentially reduces the annotation burden under a distributed setting. The proposed framework is shown to be effective compared to fully supervised scenarios with conventional data sharing instead of model weight sharing.

2.
J Med Virol ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620098

RESUMO

BACKGROUND: We analyzed antibody response patterns according to level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan. METHODS: We analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). IgM and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays. FINDINGS: The peaks of fitting curves for the optical density (OD) values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cutoff values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases. CONCLUSION: Our findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases. This article is protected by copyright. All rights reserved.

3.
J Infect Chemother ; 27(1): 70-75, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32950393

RESUMO

OBJECTIVES: The symptoms of Coronavirus disease 2019 (COVID-19) vary among patients. The aim of this study was to investigate the clinical manifestation and disease duration in young versus elderly patients. METHODS: We retrospectively analyzed 187 patients (87 elderly and 100 young patients) with confirmed COVID-19. The clinical characteristics and chest computed tomography (CT) extent as defined by a score were compared between the two groups. RESULTS: The numbers of asymptomatic cases and severe cases were significantly higher in the elderly group (elderly group vs. young group; asymptomatic cases, 31 [35.6%] vs. 10 [10%], p < 0.0001; severe cases, 25 [28.7%] vs. 8 [8.0%], p = 0.0002). The proportion of asymptomatic patients and severe patients increased across the 10-year age groups. There was no significant difference in the total CT score and number of abnormal cases. A significant positive correlation between the disease duration and patient age was observed in asymptomatic patients (ρ = 0.4570, 95% CI 0.1198-0.6491, p = 0.0034). CONCLUSIONS: Although the extent of lung involvement did not have a significant difference between the young and elderly patients, elderly patients were more likely to have severe clinical manifestations. Elderly patients were also more likely to be asymptomatic and a source of COVID-19 viral shedding.


Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Eliminação de Partículas Virais , Adulto , Fatores Etários , Idoso , Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
5.
Eur Radiol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146796

RESUMO

OBJECTIVES: The early infection dynamics of patients with SARS-CoV-2 are not well understood. We aimed to investigate and characterize associations between clinical, laboratory, and imaging features of asymptomatic and pre-symptomatic patients with SARS-CoV-2. METHODS: Seventy-four patients with RT-PCR-proven SARS-CoV-2 infection were asymptomatic at presentation. All were retrospectively identified from 825 patients with chest CT scans and positive RT-PCR following exposure or travel risks in outbreak settings in Japan and China. CTs were obtained for every patient within a day of admission and were reviewed for infiltrate subtypes and percent with assistance from a deep learning tool. Correlations of clinical, laboratory, and imaging features were analyzed and comparisons were performed using univariate and multivariate logistic regression. RESULTS: Forty-eight of 74 (65%) initially asymptomatic patients had CT infiltrates that pre-dated symptom onset by 3.8 days. The most common CT infiltrates were ground glass opacities (45/48; 94%) and consolidation (22/48; 46%). Patient body temperature (p < 0.01), CRP (p < 0.01), and KL-6 (p = 0.02) were associated with the presence of CT infiltrates. Infiltrate volume (p = 0.01), percent lung involvement (p = 0.01), and consolidation (p = 0.043) were associated with subsequent development of symptoms. CONCLUSIONS: COVID-19 CT infiltrates pre-dated symptoms in two-thirds of patients. Body temperature elevation and laboratory evaluations may identify asymptomatic patients with SARS-CoV-2 CT infiltrates at presentation, and the characteristics of CT infiltrates could help identify asymptomatic SARS-CoV-2 patients who subsequently develop symptoms. The role of chest CT in COVID-19 may be illuminated by a better understanding of CT infiltrates in patients with early disease or SARS-CoV-2 exposure. KEY POINTS: • Forty-eight of 74 (65%) pre-selected asymptomatic patients with SARS-CoV-2 had abnormal chest CT findings. • CT infiltrates pre-dated symptom onset by 3.8 days (range 1-5). • KL-6, CRP, and elevated body temperature identified patients with CT infiltrates. Higher infiltrate volume, percent lung involvement, and pulmonary consolidation identified patients who developed symptoms.

6.
J Infect Chemother ; 26(11): 1220-1223, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32792249

RESUMO

Coronavirus disease 2019 (COVID-19) is spreading worldwide and poses an imminent threat to public health. We encountered 2 cases of COVID-19 with progression resulting in severe respiratory failure and improvement without any specific treatment. To examine the course of infection, we performed reverse-transcription (RT) polymerase chain reaction assay with serum specimens, and serum SARS-CoV-2 RNA was detected in both cases when body temperature increased and respiratory status deteriorated. We, then examined, retrospectively and prospectively, the clinical course during hospitalization by performing serial examinations of serum SARS-CoV-2 RNA status. The findings from our cases suggest that not only is detection of viremia useful as a predictive marker of severity, but also serial serum SARS-CoV-2 RNA results can be helpful for predicting the clinical course.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , RNA Viral/sangue , Insuficiência Respiratória/diagnóstico , Viremia/diagnóstico , Adulto , Idoso , Betacoronavirus/genética , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , RNA Viral/isolamento & purificação , Insuficiência Respiratória/sangue , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Fatores de Tempo , Viremia/complicações , Viremia/virologia
7.
Nat Commun ; 11(1): 4080, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796848

RESUMO

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Artificial intelligence (AI) has the potential to aid in rapid evaluation of CT scans for differentiation of COVID-19 findings from other clinical entities. Here we show that a series of deep learning algorithms, trained in a diverse multinational cohort of 1280 patients to localize parietal pleura/lung parenchyma followed by classification of COVID-19 pneumonia, can achieve up to 90.8% accuracy, with 84% sensitivity and 93% specificity, as evaluated in an independent test set (not included in training and validation) of 1337 patients. Normal controls included chest CTs from oncology, emergency, and pneumonia-related indications. The false positive rate in 140 patients with laboratory confirmed other (non COVID-19) pneumonias was 10%. AI-based algorithms can readily identify CT scans with COVID-19 associated pneumonia, as well as distinguish non-COVID related pneumonias with high specificity in diverse patient populations.


Assuntos
Inteligência Artificial , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Aprendizado Profundo , Feminino , Humanos , Imageamento Tridimensional/métodos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto Jovem
8.
J Clin Microbiol ; 58(9)2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32636214

RESUMO

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.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Imunoensaio , Técnicas de Amplificação de Ácido Nucleico , Pneumonia Viral/diagnóstico , Saliva/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/análise , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Técnicas de Laboratório Clínico/estatística & dados numéricos , Feminino , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Imunoensaio/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Técnicas de Amplificação de Ácido Nucleico/estatística & dados numéricos , Pandemias , RNA Viral/análise , RNA Viral/genética , Sensibilidade e Especificidade , Manejo de Espécimes , Adulto Jovem
9.
Lancet Infect Dis ; 20(9): 1043-1050, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32539988

RESUMO

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.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico por imagem , Linfopenia/complicações , Pandemias , Pneumonia Viral/diagnóstico por imagem , Síndrome Respiratória Aguda Grave/diagnóstico por imagem , Adulto , Idoso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Hospitais , Humanos , Japão , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/virologia , Navios , Tomografia Computadorizada por Raios X
10.
J Clin Virol ; 128: 104393, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387968

RESUMO

BACKGROUND: We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). METHODS: We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-COV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. FINDINGS: Of the139 COVID-19 serum specimens, IgM was detected in 27.8 %, 48.0 %, and 95.8 % of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3 %, 8.0 %, and 62.5 %, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4 % (26/38) for the asymptomatic patients and 74.3 % (55/74) and 82.4 % (61/74) for the symptomatic patients, respectively. CONCLUSION: The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumonia Viral/diagnóstico , Adulto , Idoso , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/virologia , Feminino , Humanos , Imunoensaio/métodos , Japão , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/virologia , Sensibilidade e Especificidade , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
11.
Front Microbiol ; 9: 2748, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483243

RESUMO

Introduction: Whole genome sequencing (WGS) of influenza viruses is important for preparing vaccines and coping with newly emerging viruses. However, WGS is difficult to perform using conventional next-generation sequencers in developing countries, where facilities are often inadequate. In this study, we developed a high-throughput WGS method for influenza viruses in clinical specimens with the MinION portable sequencer. Methods: Whole genomes of influenza A and B viruses were amplified by multiplex RT-PCR from 13 clinical specimens collected in Tokyo, Japan. Barcode tags for multiplex MinION sequencing were added with each multiplex RT-PCR amplicon by nested PCR with custom barcoded primers. All barcoded amplicons were mixed and multiplex sequencing using the MinION sequencer with 1D2 sequencing kit. In addition, multiplex RT-PCR amplicons generated from each clinical specimen were sequenced using the Illumina MiSeq platform to validate the performance of MinION sequencer. The accuracy, recall, and precision rates of MinION sequencing were calculated by comparing the results of variant calling in the Illumina MiSeq platform and MinION sequencer. Results: Whole genomes of influenza A and B viruses were successfully amplified by multiplex RT-PCR from 13 clinical samples. We identified 6 samples as influenza type A virus H3N2 subtype and 7 as influenza B virus Yamagata lineage using the Illumina MiSeq platform. The overall accuracy, recall, and precision rates of the MinION sequencer were, respectively 99.95%, 89.41%, and 97.88% from 1D reads and 99.97%, 93.28%, and 99.86% from 1D2 reads. Conclusion: We developed a novel WGS method for influenza A and B viruses. It is necessary to improve read accuracy and analytical tools in order to better utilize the MinION sequencer for real-time monitoring of genetic rearrangements and for evaluation of newly emerging viruses.

12.
Intern Med ; 56(10): 1259-1264, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28502948

RESUMO

We present a case of cryptococcosis with adrenal insufficiency and meningitis in a healthy host without any risk factors. Antifungal therapy did not reduce the cryptococcal antigen titers of the cerebrospinal fluid and serum or the bilateral adrenal gland enlargement. It was suggested that the adrenal glands were the focus of persistent fungemia. Removal of both adrenal glands brought about a response to antifungal therapy. We conclude that if antifungal therapy is ineffective, bilateral adrenalectomy is an effective measure for treatment of such patients. Cryptococcosis is a possible cause of primary adrenal insufficiency in immunocompetent patients.


Assuntos
Doença de Addison/diagnóstico , Doença de Addison/tratamento farmacológico , Antifúngicos/uso terapêutico , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Meningite/diagnóstico , Meningite/tratamento farmacológico , Doença de Addison/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Grupo com Ancestrais do Continente Asiático , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Fungemia/diagnóstico , Fungemia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
14.
J Med Virol ; 83(4): 568-73, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21328369

RESUMO

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.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Virologia/métodos , Adulto , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
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