Tipo
Artigos em Revista
Tipo de Documento
Artigo Completo
Título
Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies
Participantes na publicação
Miquéias Lopes-Pacheco (Author)
Dep. Química e Bioquímica
BioISI
Pedro Leme Silva (Author)
Fernanda Ferreira Cruz (Author)
Denise Battaglini (Author)
Chiara Robba (Author)
Paolo Pelosi (Author)
Marcelo Marcos Morales (Author)
Celso Caruso Neves (Author)
Patricia Rieken Macedo Rocco (Author)
Resumo
Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.
Data de Submissão/Pedido
2020-08-11
Data de Aceitação
2021-01-08
Data de Publicação
2021-01-28
Instituição
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Suporte
Frontiers in Physiology
Identificadores da Publicação
Editora
Frontiers Media SA
Volume
12
Fascículo
593223
Identificadores do Documento
DOI -
https://doi.org/10.3389/fphys.2021.593223
URL -
http://dx.doi.org/10.3389/fphys.2021.593223
Keywords
ACE2
coronavirus
lung
multiple organ dysfunction
pathophysiology
SARS-CoV-2
therapy
viral infection
ACE
coronavirus
lung
multiple organ dysfunction
pathophysiology
SARS-CoV-2
therapy
viral infection
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