COVID-19: Pathogenesis With Sean Elliott, MD mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org) COVID-19: Pathogenesis Two main processes drive the pathogenesis of COVID-19: Early infection Driven by the replication of SARS-CoV-2 mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org) COVID-19: Pathogenesis Two main processes drive the pathogenesis of COVID-19: Early infection Later infection Driven by the replication of SARS-CoV-2 Driven by an exaggerated immune/inflammatory response to the virus that results in tissue damage mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org) COVID-19 Pathogenesis Two methods to enter cell: • Membrane fusion • Endocytosis SARS-CoV-2 ACE-2 receptor RNA Endoplasmic reticulum © by Lecturio Powered by TCPDF (www.tcpdf.org) mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Role of Angiotensin-converting Enzyme 2 (ACE-2) in COVID-19 SARS-CoV-2 attaches to the host cell by binding it's S protein to the receptor protein, angiotensinconverting enzyme 2 (ACE-2). ACE-2 is expressed by epithelial cells of various organs: Proteolytic cleavage of the S protein by host cell derived proteases (e.g., TMPRSS2) is essential to permit fusion of virus to cell membrane. Type II pneumocytes (most abundantly) © by Lecturio Powered by TCPDF (www.tcpdf.org) mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Blood vessels Kidney Intestine Role of Angiotensin-converting Enzyme 2 (ACE-2) in COVID-19 SARS-CoV-2 entry into host cell Internalization of the receptor ACE-2 inhibition ADAM17 gene expression Cytokine storm Release of tumor necrosis factor α and cytokines (interleukins, interferon) mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org) Role of Angiotensin-converting Enzyme 2 (ACE-2) in COVID-19 • • High levels of ACE-2 expression are associated with: • Certain chronic conditions, especially cardiovascular disease • Higher risk of severe COVID-19 Effects of the down-regulation of ACE-2: • ACE-2 is a negative regulator of the renin-angiotensin-aldosterone system (RAAS), and its downregulation directly affects cardiovascular function. • ACE-2 has a direct protective role in alveolar epithelial cells, and its reduction leads to alveolar cell damage. mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org) COVID-19: Pathogenesis Memory cells +Cytokines Macrophage MHC I/II CD4+ T cells TCR Dendritic cell T cell Antibodies B cells APC Epithelial cell CD8+ T cells © by Lecturio Powered by TCPDF (www.tcpdf.org) mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Plasma cells COVID-19: Pathogenesis Pneumocyte type II Red blood cells Neutrophils Macrophage Proteinaceous fluid Lungs Cytokine storm Alveolus Alveolus © by Lecturio Powered by TCPDF (www.tcpdf.org) mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. This document is a property of: mahnoor ayesha Note: This document is copyright protected. It may not be copied, reproduced, used, or distributed in any way without the written authorization of Lecturio GmbH. mahnoor ayesha, mahnoorayesha51@gmail.com © www.lecturio.com | This document is protected by copyright. Powered by TCPDF (www.tcpdf.org)
