RESUMO
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Genética Reversa/métodos , Idoso , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Fibrose Cística/patologia , DNA Recombinante , Feminino , Furina/metabolismo , Humanos , Imunização Passiva , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Mucosa Nasal/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Sistema Respiratório/patologia , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Células Vero , Virulência , Replicação Viral , Soroterapia para COVID-19RESUMO
Viruses are the most common cause of acute lower respiratory tract. The respiratory syncytial virus infection is most commonly associated with viral bronchiolitis. Rhinovirus and coronavirus OC43 are less frequently responsible for lower respiratory tract infections. The virological spectrum has expanded greatly owing to the development of molecular biology techniques. We report the clinical case of a four-month-old infant who presented with acute lower respiratory infection with coronavirus OC43 (HCoV-OC43) and rhinovirus complicated by a particularly extensive spontaneous pneumomediastinum.