a short review of COVID 19 including the epidemiology, dianosis, treatment.

1. 5/15/2020

2. Introduction:
• Definition:
• Corona (Latin = crown).
• CoVs are members of the Nidovirales order, single-
stranded, positive-sense RNA viruses (+)ssRNA.
• Are viruses that commonly cause mild but
occasionally more severe communityacquired acute
respiratory infections in humans.
• CoVs also infect a wide variety of animals including
{pigs, cows, cats, dogs, rats, and chicken} and cause
an infection to their respiratory, enteric, hepatic, and
neurological diseases.

3. 4 types of CoronaVirus (CoVs) are:
1. Alpha “α - CoronaVirus”.
2. Beta “β - CoronaVirus”.
3. Gamma “γ - CoronaVirus”.
4. Delta “δ - CoronaVirus”.
Alpha “α” and Beta “β” - CoVs”
originated from bat and rodents.
Gamma “γ” and Delta “δ” - CoVs”
originated from avian and birds.
• N.B: All Beta
coronaViruses are
dangerous to human it
leads to a severe respiratory
distress syndrome.

4. Epidemiology CoVs:
• In (2002-2003) “Severe Acute Respiratory Syndrome” - SARS
CoVs.
• In (2013) “Middle East Respiratory Syndrome” - MERS.
• In (2019) “SARS-CoVs 2” - COVID-19.
BAT
BAT
BAT
HUMAN
HUMAN
HUMAN
Palm CIVET
CAMEL
PANGOLIN
???

5. • Mean age 49 – 56year.
• Children are asymptomatic or mild symptoms.
• Ratio of affect: Male = females.
• People with risk factor for increased mortality
rate are:
1. AGE.
2. DIABTIC MELLITUS.
3. HEART DISEASE.
4. CHRONIC KIDNEY DISEASE.
5. CHRONIC LUNG DISEASE.

6. • Dec/2019 – Wuhan “ a huge un usual cases of pneumonia admitted in
Wuhan hospital.
• 13/1/2020 – First cases outside china was found in Thailand.
• 20/1/2020 – First cases found in US.
• 24/1/202 0 – Cases found in Europe.
• 30/1/2020 – COVID was so named SARS-CV2 and originated from bat
and WHO declared a public health emergency outbreak of this virus.
• 2/2/2020 – First death outside china was Philippines.
• 15/2/2020 – First death in Europe was in France.
• 19/2/2020 – CIVID-19 outbreak in Iran.
• 11/3/2020 – COVID -19 declared a global pandemic.
• 20/3/2020 – Italy was a large death cases than China.
• 26/3/2020 – Number of cases globally >500,000.
• 29/3/2020 – US was the highest number of cases followed by Italy and
Spain.
• 2/4/2202- Number of cases globally >1,000,000 and cases continue.

9. Morphology of CoVs:
Large (30Kb) single-stranded (+) RNA
Nucleocapsid protein (N), that
encloses (+) ssRNA.
Envelope embedded with proteins
(M, E)
Spikes “glycoproteins”
N.B “ The envelope of the virus can be easily destroyed
or inactivated outside the host by Soap, Alcohol, and
Disinfectant ”

10. Mode of Transmission:
1. Feco-oral transmission.
2. Respiratory droplets.
3. Direct contact “touching hand shaking”
4. Indirectly via fomites.

11. Incubation period:
• From 2- 14 days after that the classical sign and
symptoms develops.
Rate of COVID -19 Spread:

12. • Host jumping causes a Mutation of the spikes to facilitates
for binding the virus to human (host cells).
• The virus receptors and the human cell receptor must be fit
together in order to progress the disease as a “key and Log
phenomena”.

13. L o c a t i o n s O f A n g i o t e n s i n
C o n v e r t i n g E n z y m e 2 R e c e p t o r s :
• COVID -19 virus attacks these ACE2 receptors:
1. Type 2 alveolar cells.
2. Enterocytes “cells of small intestine”.
3. Endothelial cells of arterial and veins.
4. Nervous system (cerebral cortex, striatum,
hypothalamus and brainstem).

14. Mechanism Action of COVID -19 on
human cells:
Step 1:
• 1a= Binding coronavirus with Angiotonsin Converting
Enzyme 2 (ACE2) present on the alveolar type II cell.
• 1b= or coronavirus enter the cell as endocytosis.
Step 2:
• Release of coronavirus genome (+) ssRNA into the
cytoplasm then attachment to the free ribosomal of the
host cell.
Step 3:
• 3a= The free ribosome with (+) ssRNA attaches to the
rough endoplasmic reticulum from this the process of
translation begins means “formation of viral proteins”.

15. • 3b= know the viral proteins are synthesized and transferred
to the Golgi apparatus where processing, packaging of viral
content take place.
• 3c= Release of mature proteins from the Golgi to the
cytoplasm but it further processed.
Step 4:
• The enzyme proteases cleaves these proteins and make it
the final component of the viral structure these include
“spikes, envelope, viral enzymes and M, E proteins”.
Step 5:
• The RNA dependent RNA polymerase (RNA- D -RNA
polymerase) an enzyme present in the host cell causes to
copy or duplicates more and more of the (+) ssRNA.
• N.B; some scientist say that RNA dependent RNA
polymerase is formed from the free ribosome of the host.

16. • Step 6:
• Each genome (+)ssRNA and viral structure proteins are
added together to produce a mature coronavirus.
Approximately ~ > 10 cronavirus may be produced from one
alveolar cells.
• Step 7:
• Rupture of the alveolar type II cells and release the
pathogenic coronavirus that can infect other normal cell
and the cycle continue starting from step 1 – step 7.
SEARCH: Does the reproductive cycle of viral genome
containing RNA and those viral genome containing DNA
have the same mechanism or not?
from step 7

17. Binding of COVID-19 &
Angiotensin converting
enzyme receptor.
Endocytosis
Release of genome
(+) ssRNA
Binding viral genome
with host ribosome.
Formation of viral
component & processing
proteases cleaves
proteins makes the
final component of
the viral structure
RNA dependent
RNA polymerase
gives copy of
(+)ssRNA
Adding all the
viral structure
together and
rupture of the
alveoli

18. 1) Injured cell releases Interferon's (IFN), Cytokines, and
intracellular components called “Damaged Associated
Membrane Particles (DAMP)”.
2) Interferon's send signals to normal neighbor cells for preparing
to antiviral defense also causes “lymphocytopenia” because it
inhibit lymphocyte proliferation.
3) Cytokines and DAMPs binds to and activates the Alveolar
macrophages to release [cytokines, Tumor Necrotizing
Factors (TNFα), and Interleukins = IL 1, IL 6, IL 8].
4) These inflammatory processes activates a nerve ending in the
lung parenchyma's to initiates a cough reflex. These patient
have a DRY COUGH but later become productive cough.
5) TNFα and IL 1 activates a endothelial cells beneath the alveoli
for increasing adhesion molecules and increases vascular
permeability by giving a large gap between endothelial cells.
Mechanism Action of Inflammatory
Response on human cells:

19. 6) The adhesion molecules on the endothelial cells recruitment
binding and movement of netrophils and monocyte to the
injured site.
7) IL 8 directs the neutrophils to the injured site by a process
known as “chemotaxis”.
8) The increased vascular permeability leads leakage of fluid into
the interstitial space causing interstitial edema which passes
into the alveoli causing alveolar edema known as “pulmonary
edema”
9) These patient with pulmonary edema develop into DYSPNEA
AND HYPOXIA, due to mismatching ventilation perfusion ratio.
The cause of dyspnea and hypoxia is due to decreases
solubility of gases {O2}.
10) Neutrophils that entered the alveolar cells determines the
COVID-19 and engulfs it after a few second the neutrophils
rupture and releases Toxin by product, cytokines to the
neighboring cells as a result there is a massive destruction of
alveolar cell especially type 2 which leads to production of less
surfactant.

21. 11) These patient with decreased surfactant have a “lung
collapse” due to increased the surface tension of that
alveoli.
12) The damaged alveolar, macrophage, and neutrophils all
of these releases leukotrines and prostaglandins (PGs).
13) Leukotrines causes a “Bronchoconstrictions”.
14) Pulmonary edema (viscous resistance)+ lung collapse
(elastic resistance)+ bronchoconstriction (airway
resistance) = increase in work of breathing.
15) Prostaglandins, TNFα, IL 1,6 all of these causes FEVER.
16) Hypoxemia stimulates the chemoreceptor's present in
the carotid and aortic bodies firing and development of
action potential on this nerve toward the central nervous
system interpreting and sends response to the lung for
hyperventilation and heart for increasing heart rate, so
the patients develops TACHYPNEA + TACHYCARDIA.

22. 17) The macrophages have a special receptors on their surface
called Toll-Like receptors; this receptors binds to the virus
and engulf, then fusion with lysosomes, now the virus are
digested and spikes are released and presented to outer
surface of the macrophage then spike proteins are
recognized by T-Helper and activates plasma cells for the
production of antibodies against for this spike proteins
this may take 28 days, but once done the antibodies are
ready and produced quickly if there is a reinfection to
COVID-19 _ this is mechanism is important during
production of vaccines.
18) IL6 stimulates for the production of Inflammatory
chemicals such as “C-reactive proteins CRP, Fibrinogen,
Hepcidin”
19) Consolidation result from accumulation of WBC, damaged
type 1,2 and fluids.

24. 20= Severe respiratory disease causes to transport all the
exudates + waste product + inflammatory chemicals to
the blood and leads a “systemic inflammatory response
syndrome (SIRS)”.
• In circulatory system there is a:
• Vasodilatation.
• vascular permeability.
• Decreased blood volume.
• Drop total peripheral resistance.
HYPOTENSION
Decreased systemic
perfusion
Multi Organ Failure

26. Sign and Symptoms:
• Main feature:
• FEVER = 99%.
• DRY COUGH = 59%.
• SHORT OF BREATH = 31%.
• Others feature:
• Respiratory system:
• Loss of smell.
• Stuffy nose.
• Sore throat.
• Mucus or phlegm.
• Chest pain.
• Face:
• Pink eye.
• Swollen eyes.
• Bluish lips or face
• Gastrointestinal system:
• Loss of taste.
• Nausea and vomiting.
• Diarrhea.
• Nervous system:
• Headache.
• Sudden confusion.
• Fainting.
• Guillain – Barre syndrome.
• Seizures.
• Musculoskeletal system:
• Body aches.
• Chills.
• Organ failure:
• Heart.
• Kidney.
• Liver.

27. • Patient with sign and symptoms of COVID-19
varies:
o 80% has a mild infection.
o 15% has a severe disease ‘dyspnea, hypoxia, and
lung change on imaging’.
o 5% has a critically ill that manifested with
‘respiratory failure, shock, and multi organ
dysfunction’.

28. Comparisonb/wcold,Flu,Allergy,
andCOVID-19

29. Diagnosis/ Investigations:
• History taking:
• Any history travels endemic areas.
• Handling patient with COVID-19.
• Presence of sign and symptoms of COVID-19.
• Vital sign:
• Elevated (heart rate, and respiratory rate).
• Decreased (blood pressure, and spO2).
• Swabs:
• (naso / oro pharyngeal swabs).
• RT-PCR (sensitivity 30-80%) it takes times; is done by
taking sample from sputum, aspiration, and blood.
• Nucleic acid amplification test (NAAT) it’s expensive up
300$ per test.

30. • Complete blood count (CBC):
• Lymphocytopenia (80%). ****
• CMB:
A) Liver function test:
• ALT.
• AST.
• Bilirubin.
B) BMP:
• Electrolyte test.
• Glucose test.
C) Renal test:
• Blood Urea Nitrogen ‘BUN’.
• Creatinine.
• Markers:
I) Procalcitonin:
• Normal level if there is only pneumonia.
• Elevated in case of COVID-19 + pneumonia infection.

31. II Inflammatory markers:
• CRP.
• ESR.
• IL-6.
• Lactate dehydrogenase ‘LDH’.
• D-Dimer.
• Ferritin.
• In case of heart hypo perfusion
• Troponin.
• CK-MB.

32. • Medical imaging:
1- Chest x-ray:
• Ground class opacity.
2- CT scan:
o Ground class opacity.
o Consolidation (due to presence of pneumonia).
o Crazy paving pattern.
3- Ultrasound:
Pleural thickening.
Increased B - lines.
Consolidation with air bronchogram.

34. Management of COVID 19:
o IV Fluid (RL , NS) slowly because the patient has a
pulmonary edema.
o Antipyretic (fever) = TYLENOL.
o REMDESIVIR – Inhibits the RNA D RNA Polymerase by
decreasing the binding nitrogen bases together.
o CHLOROQUINE – Inhibits entry of virus to the host cell.
o RITONAVIR – Inhibits the enzyme proteases.
o TOCILIZUMAB – Decreases the inflammatory process
specially the interleukins.
o CORTICOSTEROIDS – Inhibits the phospholipase A2.
o VACCINEs “Help as to produce antibodies against spike
proteins so there is no more attachment to the host cell
and facilitates the engulfment by our macrophages”

35. Precautions of COVID 19:
1. Isolation / self quarantine.
2. Wash hands with soap or disinfectant.
3. Do not touch the “T-Zone [eye, nose, and mouth]”.
4. Decrease the travel specially to the diseased area.
5. Avoid large crowding populations and stay 6 feet
from infected person.
6. Wear:
a) Mask {best N95 mask}.
b) Eye protection.
c) Grown.
d) Double gloves.

36. • References:
o WHO.
o Medscape.
o Emedicine.
o Ninja nerd medicine.
o Armandohasudungan.
o Alila medical media.