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Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19.
Polidoro, Rafael B; Hagan, Robert S; de Santis Santiago, Roberta; Schmidt, Nathan W.
  • Polidoro RB; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
  • Hagan RS; Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina, Chapel Hill, NC, United States.
  • de Santis Santiago R; Independent Researcher, Boston, MA, United States.
  • Schmidt NW; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Immunol ; 11: 1626, 2020.
Article in English | MEDLINE | ID: covidwho-646832
Semantic information from SemMedBD (by NLM)
1. Severe Acute Respiratory Syndrome CAUSES Inflammatory Response
Subject
Severe Acute Respiratory Syndrome
Predicate
CAUSES
Object
Inflammatory Response
2. Epithelial Cells PART_OF Lung
Subject
Epithelial Cells
Predicate
PART_OF
Object
Lung
3. Epithelial Cells PRODUCES cytokine
Subject
Epithelial Cells
Predicate
PRODUCES
Object
cytokine
4. Macrophage PRODUCES C0079189
Subject
Macrophage
Predicate
PRODUCES
Object
C0079189
5. Endothelium PART_OF Lung
Subject
Endothelium
Predicate
PART_OF
Object
Lung
6. interleukin- STIMULATES C0007578
Subject
interleukin-
Predicate
STIMULATES
Object
C0007578
7. interleukin- STIMULATES C1256770|7422
Subject
interleukin-
Predicate
STIMULATES
Object
C1256770|7422
8. interleukin-6 STIMULATES Cell Adhesion Molecules
Subject
interleukin-6
Predicate
STIMULATES
Object
Cell Adhesion Molecules
9. TNF STIMULATES Cell Adhesion Molecules
Subject
TNF
Predicate
STIMULATES
Object
Cell Adhesion Molecules
10. TNF STIMULATES Vascular Endothelial Growth Factors|VEGFA
Subject
TNF
Predicate
STIMULATES
Object
Vascular Endothelial Growth Factors|VEGFA
11. interleukin-6 STIMULATES Vascular Endothelial Growth Factors|VEGFA
Subject
interleukin-6
Predicate
STIMULATES
Object
Vascular Endothelial Growth Factors|VEGFA
12. cytokine AUGMENTS Bone Marrow
Subject
cytokine
Predicate
AUGMENTS
Object
Bone Marrow
13. Inflammation CAUSES Respiratory Distress Syndrom
Subject
Inflammation
Predicate
CAUSES
Object
Respiratory Distress Syndrom
14. ACE2 gene|ACE2 AFFECTS Kallikrein-Kinin System
Subject
ACE2 gene|ACE2
Predicate
AFFECTS
Object
Kallikrein-Kinin System
15. Lung Injury COEXISTS_WITH Acute Lung Injury
Subject
Lung Injury
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
16. Lung Injury CAUSES Inflammation
Subject
Lung Injury
Predicate
CAUSES
Object
Inflammation
17. Severe Acute Respiratory Syndrome CAUSES Inflammatory Response
Subject
Severe Acute Respiratory Syndrome
Predicate
CAUSES
Object
Inflammatory Response
18. Epithelial Cells PART_OF Lung
Subject
Epithelial Cells
Predicate
PART_OF
Object
Lung
19. Epithelial Cells PRODUCES cytokine
Subject
Epithelial Cells
Predicate
PRODUCES
Object
cytokine
20. Macrophages, Alveolar PRODUCES cytokine
Subject
Macrophages, Alveolar
Predicate
PRODUCES
Object
cytokine
21. Endothelium PART_OF Lung
Subject
Endothelium
Predicate
PART_OF
Object
Lung
22. interleukin-1, beta STIMULATES Cell Adhesion Molecules
Subject
interleukin-1, beta
Predicate
STIMULATES
Object
Cell Adhesion Molecules
23. interleukin-1, beta STIMULATES Vascular Endothelial Growth Factors|VEGFA
Subject
interleukin-1, beta
Predicate
STIMULATES
Object
Vascular Endothelial Growth Factors|VEGFA
24. interleukin-6 STIMULATES Cell Adhesion Molecules
Subject
interleukin-6
Predicate
STIMULATES
Object
Cell Adhesion Molecules
25. TNF STIMULATES Cell Adhesion Molecules
Subject
TNF
Predicate
STIMULATES
Object
Cell Adhesion Molecules
26. TNF STIMULATES Vascular Endothelial Growth Factors|VEGFA
Subject
TNF
Predicate
STIMULATES
Object
Vascular Endothelial Growth Factors|VEGFA
27. interleukin-6 STIMULATES Vascular Endothelial Growth Factors|VEGFA
Subject
interleukin-6
Predicate
STIMULATES
Object
Vascular Endothelial Growth Factors|VEGFA
28. cytokine AUGMENTS Bone Marrow
Subject
cytokine
Predicate
AUGMENTS
Object
Bone Marrow
29. Inflammation CAUSES Respiratory Distress Syndrome, Adult
Subject
Inflammation
Predicate
CAUSES
Object
Respiratory Distress Syndrome, Adult
30. ACE2 gene|ACE2 AFFECTS Kallikrein-Kinin System
Subject
ACE2 gene|ACE2
Predicate
AFFECTS
Object
Kallikrein-Kinin System
31. Lung Injury COEXISTS_WITH Acute Lung Injury
Subject
Lung Injury
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
32. Lung Injury CAUSES Inflammation
Subject
Lung Injury
Predicate
CAUSES
Object
Inflammation
ABSTRACT
Most SARS-CoV2 infections will not develop into severe COVID-19. However, in some patients, lung infection leads to the activation of alveolar macrophages and lung epithelial cells that will release proinflammatory cytokines. IL-6, TNF, and IL-1ß increase expression of cell adhesion molecules (CAMs) and VEGF, thereby increasing permeability of the lung endothelium and reducing barrier protection, allowing viral dissemination and infiltration of neutrophils and inflammatory monocytes. In the blood, these cytokines will stimulate the bone marrow to produce and release immature granulocytes, that return to the lung and further increase inflammation, leading to acute respiratory distress syndrome (ARDS). This lung-systemic loop leads to cytokine storm syndrome (CSS). Concurrently, the acute phase response increases the production of platelets, fibrinogen and other pro-thrombotic factors. Systemic decrease in ACE2 function impacts the Renin-Angiotensin-Kallikrein-Kinin systems (RAS-KKS) increasing clotting. The combination of acute lung injury with RAS-KKS unbalance is herein called COVID-19 Associated Lung Injury (CALI). This conservative two-hit model of systemic inflammation due to the lung injury allows new intervention windows and is more consistent with the current knowledge.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Systemic Inflammatory Response Syndrome / Severe Acute Respiratory Syndrome / Acute Lung Injury / Betacoronavirus / Lung Limits: Humans Language: English Journal: Front Immunol Year: 2020 Document Type: Article Affiliation country: Fimmu.2020.01626

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Systemic Inflammatory Response Syndrome / Severe Acute Respiratory Syndrome / Acute Lung Injury / Betacoronavirus / Lung Limits: Humans Language: English Journal: Front Immunol Year: 2020 Document Type: Article Affiliation country: Fimmu.2020.01626