Pathophysiology of COVID-19 Part 1 (SARS CoV 2) I Target cells of COVID 19 I Coronavirus life cycle I The slides will be about the following: 1. Introduction 2. Target cells of COVID 3. Pathophysiology of SARS-CoV - nasal cavity, upper respiratory tract, alveoli

2. Introduction
• Coronavirus are large, enveloped, single stranded RNA
virus found in humans, dogs, cats, birds, bats.
• It has a diameter of 90-140nm and a spike , ranging
from 9nm to 12nm .

3. Target cells
• Nasal and bronchial epithelial cells
• Type I and type II pneumocytes
• Endothelial cells of pulmonary capillaries.

4. Pathophysiology

6. Pathophysiology
1. SARS-CoV-2 enters into the nasal cavity via aerosol transmission.
2. It will bind to ACE2 on the nasal epithelial cells. ACE2 is the main
host cell receptor for viral entry into the cells and have a high
expression on the nasal epithelial cells.
3. The type 2 transmembrane serine protease (TMPRSS2)/
transmembrane protease serine 2 present on the host cell activate S
(spike) protein on the coronavirus and it will bind to ACE2 receptor.
4. This will lead to cleavage of ACE2 and uptake of virus by the
endocytosis inside the host cell.
5. Virus will release its RNA inside the cell and RNA will take over the
cell machinery to replicate itself and assemble more viruses.
6. These replicated virions will be released and infect the adjacent
cells.
7. Limited immune response when virus is in nasal cavity.
(asymptomatic)

7. 8. There is migration of the virus from the nasal epithelium to the upper
respiratory tract via the conducting airways.
9. Clinical features (fever, cough, malaise) manifest. Innate immune response
occurs when virus is in upper respiratory tract- release of CXCL10 (chemokine
ligand-10) and interferons (IFN-β and IFN-λ) from infected cells.
10. Virus disseminates into the lower respiratory tract by either (micro-
)aspiration of SARS-CoV-2 particles causes spread from the oropharynx to the
lungs (propagated by infecting the ciliated cells) or the airborne microparticles
are transported directly into the lower respiratory tract by airflow, bypassing
the upper airways.
11. Reaching the alveoli, it will target alveolar cells especially type II
pneumocytes and also the lung endothelial cells.
12. Invade these cells by the same process via ACE2 receptor and replicate and
progress the infection.
13. Inflammatory signaling molecules (cytokine storm) are released by infected
cells and alveolar macrophages to recruited T lymphocytes, monocytes, and
neutrophils at site of injury.
14. Cytokine storm consists of interleukins (IL-1, IL-6, IL-8, IL-120 and IL-12),
tumour necrosis factor-α (TNF-α), IFN-λ and IFN-β, CXCL-10, monocyte
chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α
(MIP-1α).

8. Inflammatory mechanisms, alveolar epithelial
and endothelial damage, and coagulopathy in
COVID-19

9. 15. This cytokine storm will act as a chemoattractant for
neutrophils, CD4 helper T cells and CD8 cytotoxic T cells which
will reach the site of injury by diapedesis.
16. These immune cells will fight and try to kill the virus but in
doing so it further increase the inflammation and lung injury.
17. As the disease progresses, tissue and plasma kallikreins break
the kininogen into kinin which will bind to its receptor on lung
endothelium, resulting in vascular smooth muscle relaxation and
increase in capillary permeability leading to pulmonary edema.
18. Progression of viral injury along with the host inflammatory
response leads to the damage of alveolar wall and epithelial
endothelial barrier integrity.
19. This widespread acute inflammation, lung injury, alveolar
edema and alveolar damage leads to acute respiratory distress
syndrome.
20. ARDS is characterized by bilateral lung infiltrates and severe
progressive hypoxemia.

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