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1.
Sci Rep ; 11(1): 21259, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711897

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.


Assuntos
COVID-19/complicações , Infecções por Orthomyxoviridae/complicações , Pneumonia Viral/complicações , SARS-CoV-2 , Animais , COVID-19/patologia , COVID-19/virologia , Coinfecção/patologia , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-6/sangue , Pulmão/diagnóstico por imagem , Pulmão/patologia , Mesocricetus , Orthomyxoviridae/patogenicidade , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Replicação Viral
2.
Front Immunol ; 12: 727941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504501

RESUMO

Influenza A virus infection is usually associated with acute lung injury, which is typically characterized by tracheal mucosal barrier damage and an interleukin 17A (IL-17A)-mediated inflammatory response in lung tissues. Although targeting IL-17A has been proven to be beneficial for attenuating inflammation around lung cells, it still has a limited effect on pulmonary tissue recovery after influenza A virus infection. In this research, interleukin 22 (IL-22), a cytokine involved in the repair of the pulmonary mucosal barrier, was fused to the C-terminus of the anti-IL-17A antibody vunakizumab to endow the antibody with a tissue recovery function. The vunakizumab-IL22 (vmab-IL-22) fusion protein exhibits favorable stability and retains the biological activities of both the anti-IL-17A antibody and IL-22 in vitro. Mice infected with lethal H1N1 influenza A virus and treated with vmab-mIL22 showed attenuation of lung index scores and edema when compared to those of mice treated with saline or vmab or mIL22 alone. Our results also illustrate that vmab-mIL22 triggers the upregulation of MUC2 and ZO1, as well as the modulation of cytokines such as IL-1ß, HMGB1 and IL-10, indicating the recovery of pulmonary goblet cells and the suppression of excessive inflammation in mice after influenza A virus infection. Moreover, transcriptome profiling analysis suggest the downregulation of fibrosis-related genes and signaling pathways, including genes related to focal adhesion, the inflammatory response pathway, the TGF-ß signaling pathway and lung fibrosis upon vmab-mIL22 treatment, which indicates that the probable mechanism of vmab-mIL22 in ameliorating H1N1 influenza A-induced lung injury. Our results reveal that the bifunctional fusion protein vmab-mIL22 can trigger potent therapeutic effects in H1N1-infected mice by enhancing lung tissue recovery and inhibiting pulmonary inflammation, which highlights a potential approach for treating influenza A virus infection by targeting IL-17A and IL-22 simultaneously.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anticorpos Monoclonais/imunologia , Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H1N1 , Interleucina-17/imunologia , Interleucinas/imunologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anticorpos Monoclonais/genética , Antivirais/farmacologia , Células CHO , Cricetulus , Células HT29 , Células Hep G2 , Humanos , Interleucinas/genética , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Proteínas Recombinantes de Fusão/farmacologia , Transcriptoma/efeitos dos fármacos
4.
Arch Virol ; 166(11): 3127-3141, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34529151

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which inflicts major economic losses on the global pig farming industry. Based on its similarity to highly pathogenic strains, the GDzj strain isolated in this study was predicted to be highly pathogenic. We therefore analyzed the pathogenicity of this strain experimentally in piglets. All piglets challenged with this virus experienced fever or high fever, loss of appetite, decreased food intake, daily weight loss, shortness of breath, and listlessness, and the necropsy results showed that they had experienced severe interstitial pneumonia. We then used the BAC system to construct a full-length cDNA infectious clone of GDzj, and the rescued virus displayed in vitro proliferation characteristics similar to those of the parental PRRSV strain. In summary, we successfully isolated a highly pathogenic PRRSV strain and constructed a full-length infectious cDNA clone from it, thereby providing an effective reverse genetics platform for further study of viral pathogenesis.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/etiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Animais , Cromossomos Artificiais Bacterianos , DNA Complementar/genética , Genoma Viral , Pulmão/virologia , Linfonodos/patologia , Linfonodos/virologia , Filogenia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/crescimento & desenvolvimento , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Suínos
5.
FASEB J ; 35(9): e21801, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365657

RESUMO

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein-pseudotyped (Spp) lentivirus with the proper tropism of the SARS-CoV-2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild-type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV-G) or with a deletion of the receptor-binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27-75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3-5 times more viral burden from Spp lentivirus than from VSV-G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR-γ were quickly upregulated in response to infection in the lungs as well as in macrophage-like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS-CoV-2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2-independent viral entry pathway may be recruited in the heart and aorta.


Assuntos
Macrófagos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Glicoproteína da Espícula de Coronavírus/imunologia , Doença Aguda , Células Epiteliais Alveolares/virologia , Animais , Antígeno B7-1 , Linhagem Celular , Mediadores da Inflamação , Interleucina-10 , Interleucina-6 , Lentivirus/genética , Lentivirus/isolamento & purificação , Lentivirus/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos/virologia , Masculino , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama , Células RAW 264.7 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Proteínas do Envelope Viral
6.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263736

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.


Assuntos
COVID-19/etiologia , Pneumonia Viral/etiologia , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/fisiologia , Autopsia , COVID-19/epidemiologia , COVID-19/patologia , Citocinas/biossíntese , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Modelos Biológicos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
7.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066226

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) caused by the betacoronavirus SARS-CoV-2 is now a worldwide challenge for healthcare systems. Although the leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure due to viral pneumonia and acute respiratory distress syndrome, accumulating evidence has shown that the risk of thromboembolism is substantially high in patients with severe COVID-19 and that a thromboembolic event is another major complication contributing to the high morbidity and mortality in patients with COVID-19. Endothelial dysfunction is emerging as one of the main contributors to the pathogenesis of thromboembolic events in COVID-19. Endothelial dysfunction is usually referred to as reduced nitric oxide bioavailability. However, failures of the endothelium to control coagulation, inflammation, or permeability are also instances of endothelial dysfunction. Recent studies have indicated the possibility that SARS-CoV-2 can directly infect endothelial cells via the angiotensin-converting enzyme 2 pathway and that endothelial dysfunction caused by direct virus infection of endothelial cells may contribute to thrombotic complications and severe disease outcomes in patients with COVID-19. In this review, we summarize the current understanding of relationships between SARS-CoV-2 infection, endothelial dysfunction, and pulmonary and extrapulmonary complications in patients with COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/mortalidade , COVID-19/fisiopatologia , Citocinas/metabolismo , Células Endoteliais/virologia , Endotélio Vascular/virologia , Tromboembolia/virologia , COVID-19/complicações , COVID-19/virologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Pulmão/patologia , Pulmão/virologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/patogenicidade , Tromboembolia/complicações
8.
MEDICC Rev ; 23(2): 42, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33974614

RESUMO

INTRODUCTION: Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment. OBJECTIVE: Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases. DATA ACQUISITION: We carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or inflammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites. DEVELOPMENT: Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased in senescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic inflammation is characteristic of all these conditions, reflected in a pro-inflammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, inflammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute inflammation overlap with the patient's pro-inflammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifies already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic inflammatory response marked by high serum levels of inflammatory biomarkers and a pro-inflammatory cytokine profile with decompensation of underlying diseases. In asthma, chronic eosinophilic inflammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors. CONCLUSIONS: Low-grade chronic inflammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-inflammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.


Assuntos
COVID-19/imunologia , Inflamação/imunologia , Pneumonia Viral/imunologia , Fatores Etários , COVID-19/patologia , Doença Crônica , Comorbidade , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Humanos , Inflamação/patologia , Pneumonia Viral/patologia , Fatores de Risco , SARS-CoV-2
9.
Eur J Med Res ; 26(1): 45, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990223

RESUMO

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.


Assuntos
Infecções por Adenovirus Humanos/sangue , COVID-19/sangue , Influenza Humana/sangue , Pneumonia Viral/sangue , Síndrome Respiratória Aguda Grave/sangue , Infecções por Adenovirus Humanos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/patologia , Estudos de Casos e Controles , Feminino , Hemoglobinas/análise , Humanos , Influenza Humana/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/patologia , Trombocitopenia/patologia , Adulto Jovem
10.
Immunity ; 54(6): 1186-1199.e7, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33915108

RESUMO

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Mechanistically, Notch4 suppressed the induction by interleukin-18 of amphiregulin, a cytokine necessary for tissue repair. Protection by Notch4 inhibition was recapitulated by therapy with Amphiregulin and, reciprocally, abrogated by its antagonism. Amphiregulin declined in COVID-19 subjects as a function of disease severity and Notch4 expression. Thus, Notch4 expression on Treg cells dynamically restrains amphiregulin-dependent tissue repair to promote severe lung inflammation, with therapeutic implications for COVID-19 and related infections.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Celular , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Receptor Notch4/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Anfirregulina/farmacologia , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imuno-Histoquímica , Imunomodulação/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Vírus da Influenza A/fisiologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Pneumonia Viral/patologia , Receptor Notch4/antagonistas & inibidores , Receptor Notch4/genética , Índice de Gravidade de Doença
11.
EBioMedicine ; 66: 103288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33752127

RESUMO

BACKGROUND: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. METHODS: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. FINDINGS: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. INTERPRETATION: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Itraconazol/farmacologia , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/uso terapêutico , COVID-19/etiologia , COVID-19/transmissão , Chlorocebus aethiops , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacocinética , Itraconazol/uso terapêutico , Masculino , Mesocricetus , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudo de Prova de Conceito , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento , Células Vero
12.
Cancer Cytopathol ; 129(8): 632-641, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33690991

RESUMO

BACKGROUND: Bronchoalveolar lavage (BAL) in patients with severe coronavirus disease 2019 (COVID-19) may provide additional and complementary findings for the management of these patients admitted to intensive care units (ICUs). This study addresses the cytological features of the infection and highlights the more influential inflammatory components. The correlation between pathological variables and clinical data is also analyzed. METHODS: The authors performed a retrospective analysis of the cytopathological features of BAL in 20 COVID-19 patients and 20 members of a matched cohort from a critical ICU who had acute respiratory distress syndrome caused by other pulmonary conditions. RESULTS: A comparison of the controls (n = 20) and the COVID-19 patients (n = 20) revealed that the latter had a higher neutrophil count (median, 63.8% of the cell count) with lower percentages of macrophages and lymphocytes. An increase in the expression of CD68-positive, monocytic multinucleated giant cells (MGCs) was reported; megakaryocytes were not detected on CD61 staining. Perls staining showed isolated elements. In situ RNA analysis demonstrated scattered chromogenic signals in type II pneumocytes. An ultrastructural analysis confirmed the presence of intracytoplasmic vacuoles containing rounded structures measuring 140 nm in diameter (putative viral particles). In COVID-19 patients, the clinicopathological correlation revealed a positive correlation between lactate dehydrogenase values and MGCs (r = 0.54). CONCLUSIONS: The analysis of BAL samples might be implemented as a routine practice for the evaluation of COVID-19 patients in ICUs in the appropriate clinical scenario. Additional studies using a larger sample size of patients who developed COVID-19 during the second wave of the epidemic in the autumn of 2020 are needed to further support our findings.


Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
13.
IEEE J Biomed Health Inform ; 25(6): 1892-1903, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33769939

RESUMO

This work estimates the severity of pneumonia in COVID-19 patients and reports the findings of a longitudinal study of disease progression. It presents a deep learning model for simultaneous detection and localization of pneumonia in chest Xray (CXR) images, which is shown to generalize to COVID-19 pneumonia. The localization maps are utilized to calculate a "Pneumonia Ratio" which indicates disease severity. The assessment of disease severity serves to build a temporal disease extent profile for hospitalized patients. To validate the model's applicability to the patient monitoring task, we developed a validation strategy which involves a synthesis of Digital Reconstructed Radiographs (DRRs - synthetic Xray) from serial CT scans; we then compared the disease progression profiles that were generated from the DRRs to those that were generated from CT volumes.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/patologia , Monitorização Fisiológica/métodos , Pneumonia Viral/diagnóstico por imagem , Radiografia Torácica , COVID-19/virologia , Estudos de Casos e Controles , Humanos , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
14.
Rev. esp. med. legal ; 47(1): 41-44, ene.-mar. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-202352

RESUMO

El nuevo coronavirus SARS-CoV-2 ha causado miles de muertes alrededor del mundo. La mayoría de los fallecimientos ocurren en instalaciones sanitarias; sin embargo, un número indeterminado de enfermos fallecen de manera súbita, inesperada o repentina en diversos lugares y representan casos de interés médico legal. Compartimos los hallazgos del estudio microscópico de muestras de pulmón de un caso de muerte inesperada de un paciente positivo por COVID-19 que permanecía en aislamiento domiciliario. Nuestras observaciones corroboran la endotelialitis, trombosis y angiogénesis como distintivos de la patología pulmonar de esta nueva enfermedad, hallazgos con implicaciones clínicas y terapéuticas


The new SARS-CoV-2 coronavirus has caused thousands of deaths around the world. Most deaths occur in healthcare facilities. However, an undetermined number of patients die suddenly, unexpectedly in a variety of places and are cases of medical legal interest. We share the findings of the microscopic study of lung samples from a COVID-19 positive patient who died unexpectedly at home in quarantine. Our observations confirm endothelialitis, thrombosis and angiogenesis as microscopic hallmarks of the lung pathology of this new disease. These findings have clinical and therapeutic implications


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Coronavirus/patologia , Pulmão/patologia , Pneumonia Viral/mortalidade , Achados Morfológicos e Microscópicos , Causas de Morte , Infecções por Coronavirus/mortalidade , Betacoronavirus , Pneumonia Viral/patologia , Trombose/mortalidade , Trombose/patologia , Imuno-Histoquímica
16.
JCI Insight ; 6(6)2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33600379

RESUMO

Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and SARS coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell prorepair function after lung injury remains unknown. Here, we showed that aging results in a cell-autonomous impairment of reparative Treg cell function after experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provided insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Strategies to restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.


Assuntos
Envelhecimento/fisiologia , Vírus da Influenza A , Influenza Humana/patologia , Pulmão/patologia , Pneumonia Viral/patologia , SARS-CoV-2 , Linfócitos T Reguladores/patologia , Fatores Etários , Envelhecimento/metabolismo , Animais , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Humanos , Influenza Humana/complicações , Influenza Humana/metabolismo , Influenza Humana/virologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Linfócitos T Reguladores/metabolismo
17.
Pediatr Infect Dis J ; 40(2): 91-95, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433157

RESUMO

BACKGROUND: Clinical knowledge of human adenovirus type 7 (HAdV-7) pneumonia in children remains limited. Moreover, predictors for disease severity are largely unknown. METHODS: This is a retrospective study of children hospitalized at Liuzhou Maternal and Child Health Hospital, China, with HAdV-7 pneumonia in 2018-2019. Demographics, clinical characteristics, laboratory results, and imaging data were collected. HAdV-7 was identified in plasma using whole genome sequencing, which yielded quantitative HAdV-7 sequence numbers. RESULTS: There were 204 children; 145 (71%) were <2 years of age. There were 68 children with severe pneumonia (SP) and 136 with nonsevere pneumonia (NSP). Up to 43% in SP group with respiratory failure (SP-RF) were <12 months of age. Median duration of fever before hospitalization was shorter in NSP group than SP groups (P < 0.01). Fourteen (6.9%) underwent mechanical ventilation. There was a significant difference in mean plasma HAdV-7 sequence numbers among SP-RF, SP without respiratory failure (SP-NRF), and NSP groups (2485 ± 165, 2034 ± 124, and 286 ± 35, respectively) (P < 0.01). In a logistic regression analysis, we found that elevated plasma HAdV-7 sequence numbers significantly increased the risk of severe HAdV-7 pneumonia (OR 1.80, 95% confidence interval: 1.59-2.60, P < 0.01) after adjusting for age, fever duration, platelet counts, and serum lactate dehydrogenase levels. CONCLUSIONS: Over two-thirds of children hospitalized with HAdV-7 pneumonia were <2 years of age. Approximately 40% of those with SP associated with respiratory failure were <12 months of age. Those with SP exhibited higher plasma HAdV-7 sequence numbers. Thus, plasma HAdV-7 sequence numbers have a potential in predicting severity of HAdV-7 pneumonia in children.


Assuntos
Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Pneumonia Viral/virologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pneumonia Viral/patologia , Estudos Retrospectivos
18.
PLoS One ; 16(1): e0245547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444422

RESUMO

Endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are members of the family Coronaviridae. Comparing the findings of the infections caused by these viruses would help reveal the novel characteristics of SARS-CoV-2 and provide insight into the unique pathogenesis of SARS-CoV-2 infection. This study aimed to compare the clinical and radiological characteristics of SARS-CoV-2 and endemic HCoVs infection in adult hospitalized patients with community-acquired pneumonia (CAP). This study was performed at a university-affiliated tertiary hospital in the Republic of Korea, between January 1, 2015, and July 31, 2020. A total of 109 consecutive patients who were over 18 years of age with confirmed SARS-CoV-2 and endemic HCoVs were enrolled. Finally, 19 patients with SARS-CoV-2 CAP were compared to 40 patients with endemic HCoV CAP. Flu-like symptoms such as cough, sore throat, headache, myalgia, and prolonged fever were more common in SARS-CoV-2 CAP, whereas clinical findings suggestive of bacterial pneumonia such as dyspnea, leukocytosis with left shift, and increased C-reactive protein were more common in endemic HCoV CAP. Bilateral peripherally distributed ground-glass opacities (GGOs) were typical radiologic findings in SARS-CoV-2 CAP, whereas mixed patterns of GGOs, consolidations, micronodules, and pleural effusion were observed in endemic HCoV CAP. Coinfection was not observed in patients with SARS-CoV-2 CAP, but was observed in more than half of the patients with endemic HCoV CAP. There were distinctive differences in the clinical and radiologic findings between SARS-CoV-2 and endemic HCoV CAP. Further investigations are required to elucidate the mechanism underlying this difference. Follow-up observations are needed to determine if the presentation of SARS-CoV-2 CAP changes with repeated infection.


Assuntos
COVID-19/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Estudos de Coortes , Coinfecção/diagnóstico por imagem , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Infecções Comunitárias Adquiridas , Coronavirus/isolamento & purificação , Doenças Endêmicas , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Radiografia Torácica/métodos , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Tórax/diagnóstico por imagem
19.
Virology ; 554: 97-105, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33412411

RESUMO

We examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in cynomolgus macaques for 28 days to establish an animal model of COVID-19 for the development of vaccines and antiviral drugs. Cynomolgus macaques infected with SARS-CoV-2 showed body temperature rises and X-ray radiographic pneumonia without life-threatening clinical signs of disease. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes producing interferon (IFN)-γ specifically for SARS-CoV-2 N-protein were detected on day 14 in one of three macaques with viral pneumonia. In the other two macaques, in which a neutralizing antibody was not detected, T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 N protein increased on day 7 to day 14, suggesting that not only a neutralizing antibody but also cellular immunity has a role in the elimination of SARS-CoV-2. Thus, because of similar symptoms to approximately 80% of patients, cynomolgus macaques are appropriate to extrapolate the efficacy of vaccines and antiviral drugs for humans.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , Modelos Animais de Doenças , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/patologia , COVID-19/virologia , Citocinas/sangue , Feminino , Interferon gama/imunologia , Macaca fascicularis , Masculino , Boca/virologia , Cavidade Nasal/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Carga Viral
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