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Med Hypotheses ; 146: 110412, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33308936

RESUMO

The Corona Virus Disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) requires a rapid solution and global collaborative efforts in order to define preventive and treatment strategies. One of the major challenges of this disease is the high number of patients needing advanced respiratory support due to the Acute Respiratory Distress Syndrome (ARDS) as the lung is the major - although not exclusive - target of the virus. The molecular mechanisms, pathogenic drivers and the target cell type(s) in SARS-CoV-2 infection are still poorly understood, but the development of a "hyperactive" immune response is proposed to play a role in the evolution of the disease and it is envisioned as a major cause of morbidity and mortality. Here we propose a theory by which the main targets for SARS-CoV-2 are the Type II Alveolar Epithelial Cells and the clinical manifestations of the syndrome are a direct consequence of their involvement. We propose the existence of a vicious cycle by which once alveolar damage starts in AEC II cells, the inflammatory state is supported by macrophage pro-inflammatory polarization (M1), cytokines release and by the activation of the NF-κB pathway. If this theory is confirmed, future therapeutic efforts can be directed to target Type 2 alveolar cells and the molecular pathogenic drivers associated with their dysfunction with currently available therapeutic strategies.


Assuntos
Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/virologia , COVID-19/imunologia , COVID-19/virologia , Modelos Biológicos , NF-kappa B/imunologia , SARS-CoV-2 , Células Epiteliais Alveolares/patologia , Enzima de Conversão de Angiotensina 2/fisiologia , COVID-19/etiologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Inflamação/imunologia , Inflamação/patologia , Ventilação Líquida , Macrófagos/imunologia , Macrófagos/patologia , NF-kappa B/antagonistas & inibidores , Neutrófilos/imunologia , Neutrófilos/patologia , Pandemias , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Transdução de Sinais/imunologia
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