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1.
Stem Cell Reports ; 17(5): 1089-1104, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: covidwho-1799706

RESUMO

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Pericitos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/complicações , Doenças Cardiovasculares/virologia , Células Endoteliais , Camundongos , Pericitos/metabolismo , SARS-CoV-2
2.
Front Immunol ; 11: 596631, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-1004678

RESUMO

COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome. As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2. We critically reviewed host characteristics and hyper-inflammatory response in these two viral infections to have a better insight on the large difference in clinical outcome in persons being infected by SARS-CoV-2. The better understanding of mechanism of T cell dysfunction will contribute to the development of targeted therapy against severe COVID-19 and will help to rationally design vaccine involving T cell response for the long-term control of viral infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Infecções por HIV/imunologia , Linfopenia/patologia , SARS-CoV-2/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , COVID-19/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Disbiose/patologia , Microbioma Gastrointestinal/fisiologia , Infecções por HIV/patologia , Humanos , Junções Íntimas/patologia
3.
Front Immunol ; 11: 570063, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-874478

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most infected people have mild or moderate symptoms and recover without the need for extensive treatment. However, for seriously ill patients, no specific treatments are currently available. Convalescent plasma therapy (CPT), a passive immunotherapy, involves infusing plasma from recovered people into actively infected people, and is thought to be a specific intervention to improve outcome in patients with severe COVID-19. The presumed mechanism involves neutralizing antibodies and antibody dependent cytotoxicity/phagocytosis. Previous CPT trials showed an effect in SARS and pilot studies suggest CPT is an effective and safe strategy for seriously ill COVID-19 patients. CPT is currently being tested in large randomized clinical trials. Herein, we critically review the mechanism, applications and the challenges for CPT in the treatment of severe COVID-19, paving the way toward vaccine and immunotherapy development.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/imunologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva , Plasma/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Soroterapia para COVID-19
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