PAPER PATHOPHYSIOLOGY

SARS-CoV-2 : Pathophysiology of COVID-19 and

Immune System

(Drs. M. Yanis Musdja, M.Sc)

Created By:

Muhammad Muttaqienalfahry Saptadjie (11191020000071)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS ISLAM NEGERI SYARIF HIDAYATULLAH

 Indonesia is one of the many countries that experienced a
pandemic from the SARS-CoV-2 virus outbreak or the Covid-19
pandemic. This epidemic originated in China, which until now
has been determined to be a pandemic epidemic that has claimed
thousands of lives. As the name implies, this virus will attack the
lungs as its main target. Lungs and Covid-19 are the main focus
of this. Keyword : Covid-19, Lungs, Immune cell and symptomps

Introduction

In the pandemic covid-19 that still ongoing in every nations including

Indonesia, there are so much people have been infected by this virus wether
symptomatic or asymptomaic. In early days of pandemic until right now, not a
few people are willing to stay home patiently to lowering risk of spreading the
virus and got infected even though they want to meet their freinds to chatting.
This covid-19 pandemic is caused by SARS-CoV-2, the virus that can easily
spread and infect people which target human lungs for main target. This virus can
be easily spread because the media of spreading used by virus is the droplet that
comes out from mouth (often times) and nose when someone that infected
coughing or wheezing. Moreover, the virus can attach and live at surface object
for a long time.
A. Lungs : Anatomy & Physiology
Lungs is one of the vital organ for living things. With the help of lungs,
humans and animals can live with breathing of course with other organ that can
help the function of lungs such as nose and diaphragm. The shape of lungs is
like a big balloon-like sac which coated with bilayer that can serve as cushion.
The lung’s muscle is flexible enough to be contracted and relaxed so that
enables us to breathing.

a. Anatomy
In human, lungs is located in thoracic cavity, more precisely
located in front of heart (anterior to heart). The shape of lungs is a pair
of big ballon-like sacs which have same shape (like mirror), but the left
side much smaller than the right side it is because the existence of heart
that located a little to the left. If we view from anterior (from the front),
the shape of lungs is like flat and smooth air sac with apex at the upper
side and some hint of line called fissure, the bottom side of left side
lungs is much smaller than right side. And if we view from posterior
(from the back) the shape is much like bowl, and there is hilum in the
back side of lungs. The hilum is wedge-shaped area located in central of
each lungs, the area region is where the bronchi, arteries, veins and
nerves enter and exit the lungs. Actually, there is segments in lungs
called lobes and again in the lobes there are smaller segments. The
segment in lungs is indicated by fissure. The right side of lungs is
divided into three lobes such as superior lobe (upper side), middle lobe
and inferior lobe (lower side). While in the left side of the lungs there
are only two lobes such as superior lobe (upper side) and inferior lobe
(lower side). With a help of trachea, lungs can connect to nose so that
enables lungs to do its job. Trachea or windpipe is kind of tube-like
shape that connects lungs to larynx so it can help the job of lungs to
catches air. The bottom side of trachea there is a branch called bronchi
and there is two of them. Bronchi, the branch get into the lungs via
hilum. Actually, there are also smaller branches of bronchi inside of
lungs called bronchiolus and at the end of bronchiolus, there are lot of
tiny air sacs called alveoli. The function of alveoli is for place for
exchange of carbon dioxide and oxigen in bloodstream.

Lungs is coated and protected by a thin layer called pleura. The

inner side layer of pleura that coating lungs is called pleura vescirales
meanwhile the outer side layer of pleura that lining with thoracic wall
called pleura parietalis. The between of two layers, there is tiny amount
of lubricating liquids that helps to reduce fractions between lungs and
wall.
 Inferior to lungs and heart, there is a dome-shaped like thin
musculoskeletal called diaphragm. This thin musculoskeletal is
sufficient enough to be able to contract and relaxe if needed.

b. Physiology
Basically, all of living things except plants need to breath because
they needed oxigen to stay alive. But, because oxigen is exist in
environtment, i mean in air not in body of humans nor animals but their
suroundings. It means they need ability that enables them to catch
oxigen in air. Thats why lungs existed, with the helps of lungs and other
organ that can helps lungs, so we can breathes and stay alive.

a) So how human breath? And what “other support organs”

means?
There are two mechanism of breathing, namely chest
breathing and abdominal breathing. We focus on chest
breathing. So, with the help of diaphragm and its ability of
contract and relax, it become primary organ that help the
process of breathing. Because of its ability to contract and
relaxe when breathing, it maximizes breathing process. When
human inhales (breathes in) the diaphragm will contract and
cause a vacuum effect so that the air pressure in the thoracic
cavity will be lesser than atmospheric air pressure. Because the
air pressure in the thoracic cavity is lesser than atmospheric air
pressure caused by the vaccum effect, the air from the outside
will enter and fill the thoracic cavity, so that is the inhales
process of chest breathing.

b) What is happening in the lungs when breathing? And how it

happen?
When lungs increase in size because of inhales air in
atmosphere, at the same time in alveloli, which is a place that
rich of O2 there is an exchange process between O2 and CO2.
This exchange can occurs because CO2 is a product of body
from the process of metabolism. When breathing, the O 2 will
enter into body and automatically the CO 2 will goes outside
body when breath out. This process is suppoted by a simple
diffusion that occurs in alveoli, this process called gas
exchange. After that, the blood stream that rich of O2 went to
heart and will pumped to whole body. This whole process is
 complicated but at same time it so fast that we, the human
being ignorant of this process.

B. What exactly is SARS-CoV-2?

Coronavirus Disease 2019 (COVID-19) is a respiratory tract disease that
mainly attack the lungs. This disease occurs because of the coronavirus,
namely SARS-CoV-2.

a. SARS-CoV-2
SARS-CoV-2 is one of the virus that has same category as SARS-
CoV and MERS viruses namely Coronavirus (corona : crown) because
the structure of SARS-CoV-2’s Spikes that look alike to crown. This
coronavirus was first discovered and spread in one of city in China,
namely Wuhan since Desember 2019. Since the virus spreading in
Wuhan, there is a lot of pneunomia cases that occues in wuhan however
the initial cause remains unknown. hence, the Chinese government and
researchers did various things quickly to conduct ethiological research
and to get control of endemic so the spreading of virus is restrained. In
2020 the virus breakout and spread out over countries and at february
11th 2020 WHO officially named this virus, novel Coronavirus (n-CoV)
and later this virus named SARS-CoV-2. Coronavirus SARS-CoV-2 is
mostly the same to SARS-CoV and MERS virus. In fact, the SARS-
CoV-2 belong to β-coronavirus class, which is the same class with
SARS-CoV and MERS virus. In the early days of COVID-19⸻
which is the disease that happens because the infection of SARS-CoV-2
⸻ this virus related to the seafood market in wuhan, because the
virus first spread in this seafood market. Hence, the suspectibility of
spreading method yet to be found. In the time, WHO has been claimed
a report that SARS-CoV-2 can be detected from sample that taken from
environment which has been collected from seafood market. However,
the researcher not yet found animal carrier of this virus at that time. the
research done by ji et al shows that the SARS-CoV-19 is chimeric virus
⸻it means the SARS-CoV-2 actually is derived virus from two or
more gene, genes will combined then SARS-CoV-2 will be created
⸻between bat coronavirus and unknown-origin coronavirus. A
research done by benvenuto et al shows that the coronavirus which
isolated from china chrysantheum-head bat in 2015 is the only
coronavirus that closely related to SARS-CoV-2. These two researches
supports the theory origin transmission of SARS-CoV-2 is from bat to
human. In the recently researches done by Zhou et al and Wu et al
found that SARS-CoV-2 and SARS-CoV was 79,6% same in the
sequence homolog, and higher sequence homolog between SARS-CoV-
 2 and bat coronavirus. This research strongly supports the SAS-CoV-2
was derived from bats.

b. Structure of SARS-CoV-2
Coronavirus virions are spherical with a diameter of approximately
125 nm as revealed by cryo-electron tomography and cryo-electron
microscopy. The corona viral genome encodes four main structural
proteins namely the surface spike (S) glycoprotein, the membrane (M)
protein, the small envelope (E) glycoprotein, and the nucleocapsid (N)
protein. All these proteins are required to provide the structure of
complete viral particles called virion. The spike protein is ∼180KD
glycoprotein which is present on the surface of the virus. It is crucial for
the entry of coronavirus into the host cell. It contains two subunits
namely S1 and S2. The S1 subunit binds to the receptor on the surface
of the host cell whereas S2 subunit mediates the cell membrane fusion.

c. Spreading of SARS-CoV-2
a) Media of spreading
Coronavirus SARS-CoV-2 is a type of virus that very easy
to spread between people. This happens because this virus uses
media of air to spread via droplets from infected people when
they sneezing, coughing and even talk. There are three methods
of transmission of this coronavirus. The first is from droplets,
droplets is a tiny particle that spread out when people sneeze,
cough or talk and this tiny particle of droplets can infects people
to get COVID-19. Infections occur mainly through exposure to
respiratory droplets when a person is in close contact with
someone who has COVID-19. The second method transsmission
is airbone transmission. This virus is unique because when it
spread with a media of droplets, this virus can stay live in air for
like 3 hours and because of this ability it can use air for spread
and infecting people. The third method transmission is called
surface transmission. This virus ability for stay live even if they
are in surface is amazing, they can live for 4 days at surface of
woods and 5 days at surface of metals. And someone can be
infected if they touches the surface that infected people sneeze
at and after that touches his mouth, nose or eyes. This three
transmission makes this virus easy to spread. Imagine this,
people can get infected if they near infected people from
droplets or even if someone is far enough from infected people
 they cant be guaranteed safe because of airbone transsmision
and surface transmission.

b) How easy to get infected?

Researchers said that the average infected person will
infects other in average of 2 to 2.5. in different research the
average of people got infected because infected people is higher,
its in range of 4.7 to 6.6. For the comparison the average of
measles infected people will infecting other is in range 12 to 18,
meanwhile average of flu infected people will infecting other is
in range 1.1 to 2.3. In some researches said that there is lower
chance to get infected and milder symptomps threat to a child in
comparison to adult. Although infected children still can spread
the virus to others.

d. ACE2 and its role on phatogenesis of SARS-CoV-2

a) Angiotensin II and Angiotensin-converting enzyme 2
Angiotensin II is a hormone that naturaly can be found in
body because this hormone is a natural peptide hormone that
produced from renin-angiotensin-aldosteron system (RAAS).
Angiotensine is hormone with potent vasoconstrictor, it means
this hormone is two-sided sword that have benefit and threat at
same time. this vasoconstrictor has a function to increasing
blood pressure which has benefit to mantain blood pressure if
someone has low blood pressure. Meanwhile if someone is
healthy enough and this hormone get overproduces, this hormon
will threathening body because high blood presssure.

Angiotensin-converting enzyme 2 (ACE2) is a protein,

receptor and enzyme at same time. This enzymes has a function
to converts angiotensin II that has potent vasoconstrictor to
angiotensin(1-7) to minimalize effect. In simple way, this
enzyme help regulates the activity such as regulating blood
pressure, regulating angiotensin II, regulates inflammation and
wound healing, namely RAAS. In RAAS system, ACE2 act as
an antagonis. This ACE2 will converts via hydrolizes the
angiotensin II to Angiotensin (1-7), effect of angiotensin II is
vasoconstrictor and inflammation. In other hand, effect of
angiotensin (1-7) is vasodilation and anti-inflammation. It
 means that angiotensin (1-7) will counters and neutralize the
effect of angiotensin II. Which means this ACE2 regulates blood
pressure via converting angiotensin II to angiotensin (1-7).

b) ACE2 and SARS-CoV-2

ACE2 is a protein that function as an enzyme and receptor
at same time. this enzyme function is to regulates angiotensin II,
in other hand this protein can act as receptor or morelikely a
gate-pathway of SARS-CoV-2. SARS-CoV-2 use mace-like
spikes enables the virus to binding active area of ACE2 with key
& lock method. Not only that, when SARS-CoV-2 is binding to
ACE2 active zone, it means that active zone of ACE2 is blocked
by SARS-CoV-2 so that Angiotensin II cant binds to ACE2,
therefore cant be converted to Angiotensin (1-7).

c) ACE2 distribution in tissue

Basically, organs that express higher levels of ACE2 are

susceptible to infection with SARS-CoV-2. Therefore, the
spread and abundance of ACE2 in an organ can closely tie the
clinical symptoms of COVID-19. ACE2 is very abundant in the
heart, kidneys and testes. This protein is also present and widely
distributed in the lungs, heart, intestines and brain. The lungs are
the main site of damage caused by SARS-CoV-2 infection. Most
of the patients admitted to hospital infected with the SARS-
CoV-2 virus developed pneumonia.

d) Smokes affect ACE2 expression.

The study done by Sheltzer et al and Smith et al show that
there is different in lungs condition between the healthy lungs
and smokers lungs. The healthy lung condition is in good shape,
just a normal-looking shape of lung. On other hand the smokers
lungs isnt in good shape in fact, there is a layer of mucous-like
covering the lungs called mucin. This mucin is one of secretion
that expressed by goblet cells in epithelial cell at respiratory
tract. Mucin is a mucous-like layer that has function to trap
foreign chemicals that will harm the lungs such as, nicotine and
tar that will be found cigarette. Therefore, so when somebody is
smoking, it means that the mucin expression will increased and
spread to cover lungs which means that the goblet cell
 production is increased due to expression of mucin. So the more
people smoking, the more goblet cells multiplied due to
increased expression of mucin to successfully trap these harmful
chemicals. The presence of increased goblet cells fueled a surge
in ACE2. The research done by sheltzer et al and Smith et al
show that in lung tissue sample taken by smokers has ~30%-
55% more of ACE2 compared to lung tissue of non-smokers. In
the recent study done by researchers of china, the patient with a
background of smoker is more severe than the patient with a
background of non-smoker as indicated by the severe rate
(Smoker : 29/137, 21,2 %; never-smoker/ non-smoker : 134/934,
14,5%). These data show that the smoker has higher chance to
get infected and get severe condition.

e. Patophysiological of Covid-19
These all begun when SARS-CoV-2 went into peopel respiratory
tract. Then the SARS-CoV-2 will search its receptor which is ACE2
enzyme that located in epithelial cell of the lungs. With a help of its
mace-like S-Spike SARS-CoV-2 binds to ACE2 receptor and went into
epithelial cell of lungs. When SARS-CoV-2 inserts into the body, it
injects its genetic code to the cell, which is ssRNA of virus. This
ssRNA will hijacked the ribosom in the cell to producing a ssRNA copy
and SARS-CoV-2 structure, including spikes, membrane, nucleocapsid,
envelope of the virus. This process called incubation states which
means in this process the virus has not infecting the body, but instead
makes a lot of copy, incubation will takes 4-14 days or even more to
clear based on immune system of the body. When incubation periods
complete, this virus will enter the infection proecess. In the early days
of infection, this virus will infects the endothelial cells in lungs. This
infection will produce mild symptomps like a flu symptomps include
sore throat, cough and maybe fever due to immune system response. In
the second week the infection in alveoli of lungs will be in moderate
level and due to immune responses, the symptoms will be more severe,
in this week milder pneunomia symptoms has appeared. In the next
week, the disease becomes more severe in the point where the
symptoms that the virus caused is in severe condition. From this stage
all the symptoms of the disease, such as pneunomia is in severe
conditions, in fact around 20% of Covid-19 patients has ARDS
symptoms in this week. When this virus infects and attacks the alveoli,
the immune systems at that site will trigger and release Cytokines,
which is such as Interleukin and Interferon⸺ interleukin is one of the
kinds of cytokines the messanger, this type is responsible for the
 immune response, such as inflammation which will be the cause of
pneunomia in later steps.

f. Pneunomia and other symtpoms

Everything that enter the body and infects including virus will
causes disease and of course will cause symptoms, including SARS-
CoV-2 virus. this virus will be the cause of one disease called
Coronavirus Disease 2019 (COVID-19), a disease heavily-related to
respiratory tract, especially lungs organ. This disease is heavily-related
to lungs organ, so the symptoms at least related to lungs. One of the
main symptoms is pneunomia and acute respiratory distress syndrom
(ARDS). These two symptomps found in severe Covid patients, except
for pneunomia that found in milder Covid patients.

a) What is pneunomia and how it happened?

Pneunomia is a disease that causes due to the infection
which attacks lungs, this infection can be from virus or
microbes. This disease starts from immune response that cause
inflammation in alveoli of the lungs due to infections in lungs.
This inflammation that occurs in lungs will damaging alveoli of
the lungs even whole lungs when inflammation is severe. This
inflammation reduces the air space in the alveoli which require
more breathing. When inflammation in alveoli become severe,
the fluid will leak and fill the alveoli and breathing becomes
difficult.

When Virus SARS-CoV-2 enters the body via ACE2

receptor. The virus will enter the incubation period for 4 – 14
days then later will enter infecting periods. In the early days of
infection, the symptoms caused by this virus is mild, like
coughing, sore throat and fever. A week later, this virus will
cause mild-level of pneunomia indicated by hard breathing and
short breathing. In the second week of infection, all of
symptoms include pneunomia becomes severe due to activated
immune response to kills this virus. in the third week, because
of how strong the virus is, the immune system release a lot of
cytokines, namely cytokine storm. The cytokine storm is an
immune response caused by activation of huge amount of white
blood cells due tothe infection that caused by microbes or
 viruses, the cytokines will be produced excessively resulting in
multi-organ failure due to severe inflammation in this case
though, the damaged organ will be the lungs. This kind of
chains reaction of immune response makes inflammation
becomes severe resulting that severe pneunomia or even severe
symptoms like Acute Respiratory Distress Syndrom (ARDS)
might occurred. A study of 41 hopitalized COVID-19 Patients
shows that the potent proinflammatory cytokines is in severe
cases, including IL-2, IL-7, IL-10, MCP-1, and TNFγ. COVID-
19 patients show that levels of IL-1β, IFNγ, IP-10, and MCP-1
have increased, so that Th1 cell responses becomes
hyperactivate.

b) What is ARDS and how it happen?

Acute Respiratory Distress Syndrom (ARDS) is a disease
that caused by too much fluid which fill the alveoli resulting in
breathing becomes difficult, shortness breathing, and rapid
breathing. Patients with ARDS is in severe condition so that
even oxygen becomes difficult to enter the body until in point
where patient need breathing apparatus due to fluid leaking that
fill the air space in tiny air sac, namely alveoli. This disease has
founded within a patients with respiratory-related disease, in this
case is severe pneunomia due to SARS-CoV-2.

How is the connection between ARDS and SARS-CoV-2?

When SARS-CoV-2 enter the body via ACE2 receptor, the
virus will enter the incubation for 4 – 14 days and then later will
enter the infection period. SARS-CoV-2 infection in the first
and second week of infection is a mild one, the symptoms
caused by infection is rather a mild to moderate one such as sore
throat, cough, fever, mild pneunomia, and myalgia. The third
week is the severe one, in this week everything keeps worsening
without any signs of getting better. In this week, there is
activation cytokines storm due to large amount of activation
white blood cells so that the inflammation of the alveoli gets
worse, this causes pneunomia to become severe. The
inflammation of the alveoli is so severe that the fluid in blood
vessels began to leak and fill up after few days. In fact, around
15 patients of 75 Covid-19 patients have ARDS after three
weeks of being infected of SARS-CoV-2.
 Critically ill patients with ARDS have difficult to collecting
oxygen while breathing, this is happened due to the fluid and
free-hemogoblin cell (hemoglobin is the carrier of oxygen in
blood vessels) that fills up tiny air sacs of the lungs. A study
done by Shaver et al shows that a patient with ARDS has signs
of hemolysis, free-hemogoblin cells, and edema.
c) Heart failures
In severe Covid-19 patients, there is a chance the patients
has a cardiavascular failure. This occurs because of the excess
cytokines that have been released from the cytokine storm to
attack SARS-CoV-2, the type of cytokine that is mostly released
is Interleukin, including interleukin 1 family. This excess IL-1
will eventually flow out to the blood system. When IL-1 are in
the cardiovascular system, the interleukin will binds to its target
receptor in the surface of membrane and will give cascade
signal. The signal effect that released from IL-1 is a vasodilation
effect. This effect will dilating the blood vessels membrane so
that the blood fluid will leak out of blood vessels. Which leads
to septic shock. The septic shock is a severe condition when the
inflammation occurs in bloodstream resulting in heart fails
because of its inability to keep and raise blood pressure so that
blood pressure continues to drop due to the dilation and
increased permeability membrane of blood vessels, which leads
to multi-organ failures and ultimately lead to death.

C. Immune system
Immune cells are cells that are responsible for defending the body against
foreign objects, in this case the SARS-CoV-2 corona virus. These cells are very
many types and have different functions including the epithelial / endothelial
immune system as the first line of defense, cytokines as mediators,
macrophages (leukocytes) as phagocytic cells, while T cells and B cells
(lymphocytes) are the last defense as well as the main weapon. to fight the
virus.

a. Steps of Immune System in Human Body

The innate imunity and immune systems are the body's first
defense systems against foreign things. This immune system
belongs to a non-specific initial defense mechanism. The
epithelial immune system (epithelial immune system) is a
defense system that exists outside the body and its nature is
physical defense. While the cellular immune system is a defense
 system that is located in cells (in the body) and is chemical
defense

The innate immune system is the body's outermost defense

system and is outside the body's cells. A simple example of the
epithelial cell immune system is the presence of tiny hairs and
mucus in the nose which are useful as a hold on inhaled foreign
objects such as dust and others from entering the body. After the
foreign object is caught, the immune response given is to wrap
the foreign object in mucus or remove it from the body by
sneezing.

The cellular immune system is an immune system that is in

the cells consisting of various systems that help each other in a
complex response. This immune system is included in a non-
specific defense system that protects the body from microbes
that enter the body. This system consists of: mast cells,
endothelial cells, macrophages, NK and platelets. This way of
explaining the immune system may be difficult to explain, but
simply begins when the skin is exposed because of an injury.
The cut in the skin creates an opening in the skin that allows
bacteria to enter the cells. NK and macrophages are responsible
for eliminating microbes by means of phagocytes. On the other
hand, mast cells will release two compounds called histamine
and interleukin, where these two compounds are responsible for
helping the immune system. Histamine will bind to endothelial
cells in cells, histamine functions to enlarge blood vessels
(vasodilation) and interleukins function to activate the T & B
lymphocyte system. The T lymphocytes will attack the microbes
or viruses, in the other hand the B lymphocytes will make
antibodies from the data of that antigen, this antibodies will
mark down the antigen so immune system can focus to attack
that antigen. After all bacteria have been killed by the immune
system, the next step is the function of tombocytes. Platelets
function in closing the wound with fibrin tissue that is secreted
by broken platelets called thromboplasts.

b. The role of T cells

T cells are one of the two cells produced by lymphocytes. T cell is
an immune cell whose job is divided into two types according to the
type of T cell. T cells are divided into five types, namely CD8 +, CD4
+, regulatory T cells, memory T cells, Neutral killer T cells (NK cells /
 NK cells) and. CD8 + T cells and NK cells are the types of T cells that
are at the forefront of the immune system and CD4 + T cells are right
behind them when the situation gets out of hand. Meanwhile, regulatory
T cells and memory T cells work behind the scenes. CD8 + T cells / the
killer have the ability and responsibility to kill viruses and microbes in
the body, such as viruses and microbes. CD4 + T cells / the helper have
the ability and responsibility to assist the immune system in defeating
viruses or microbes that resides in the body, by producting factors that
activates all the other immune system cells, including antibodies carried
out by B cells. NK cells have the ability and are responsible for
recognizing and differentiating cancer cells or cells. infected from
normal body cells and attack cells that are not body cells. Regulatory T
cells work behind the scenes and monitor the activity of the immune
system and the immune response that occurs in the body, the function
of these regulatory T cells is to stop all kinds of excess immune activity
while defeating the virus. Memory T cells also work behind the scenes
like regulatory T cells, but their functions and abilities are very
different, regulatory T cells are in charge of stopping immune activity
because viruses / bacteria have been successfully destroyed (followed
by the cell healing process), while memory T cells are responsible for
remembering and recognize viruses / bacteria if the virus / bacteria re-
enter the body so that the immune system can work optimally.

In SARS-CoV-2 case, the research done by a group of researchers

of Dr. Juliane Walz at the Clinical Cooperation Unit Translational
Immunological (KKE) has founded the roles of T Cells. The part of the
T Cells namely T cells epitopes is important roles for identifying and
diagnose the SARS-CoV-2 structure. The researchers group leader Dr.
Juliane walz said that, this finding of T Cells epitopes is important for
identification and diagnosis of SARS-CoV-2, this epitopes is also
important for the vaccines development.

c. Can immune system defeat SARS-CoV-2?

Yes it can, hypothetically immune system alone can defeat SARS-
CoV-2. The reason that SARS-CoV-2 can not be defeated and
symptoms becomes severe in later weeks is because people immune
system is overwhelmed by SARS-CoV-2, either by low immunity level
or high amount of SARS-CoV-2 in body. These two reason make it
impossible to defeat the virus and disease becomes more severe in later
weeks. However, this virus is not impossible to be defeated, there is a
chance to be recovered without using medicines and vaccines. This can
happen when infected people’s immune and antibody level is so high
 that in point where immunity and antibody level is sufficient to
overcome phatogenicity of SARS-CoV-2. So, the person who has been
infected by SARS-CoV-2 are able to recover. A study that has been
done by researchers from the University of Melbourne at the Peter
Doherty Institue for Infection and Immunity in Australia shows that
there is a chance to be recover from Covid-19. The researchers found in
a body of infected 47-year old female that there is an influx in a crucial
immune system, there was an in increase in IgM and IgG, and a large
number of speciallized Helper T Cells, Killer T Cells and B cells at
days 7-9 following symptom onset. The increase in antibodies persist
up to day 20 after symptom onset, according to the analyses. This study
and founding supported that there is a way to recover from Covid-19
with Immune level and immune systems.

D. Prevention
People who is not get infection from SARS-CoV-2 can prevent themselves
by take care of themselves. This is how to prevent yourself from the infection
of
a) Wear a mask
Sometimes the simplest way is the best way to solve something.
The SARS-CoV-2 is spreading via the droplet, airbone transmission,
and surface transmisssion, but mostly the infections comes from
droplets. When people wear a mask it actually decrease the risk to get
infection of this virus so be sure wear a mask if you go somewhere.
b) Stay at home
Stay at home is the good prevention to get infection of this virus,
and it does decrease the risk and infection rate of SARS-CoV-2 virus..
c) Don’t go to the crowd
The risk to get infection significantly increase in the crowd,
because we can’t be so sure if people in crowd is completely healthy.
So don’t go to the crowd and make sure to keep distance so the risk to
get infection is low.

d) Keep doing good lifestyle

The best solution and prevention is keep doing good lifestyle and
maintaining our immune. manages sleep schedule, level stress, and
takes Vitamin C is a good way to maintains immunity of your body.
Vitamin C is a highly effective antioxidant due to its ability to readily
donate electrone, Vitamin C is also has significant role in immune
defense. One of the role is enhance antibody levels, enhances
phagoticity and ROS production which is used in immune system, and
enhances differentiation and proliferation rate of lymphocytes cell.
E. Conclusion
This paper discussing about lungs, SARS-CoV-2 and patophysiology of
covids, immune system and prevention steps. The virus SARS-CoV-2 virion
structure is ball-like virus with a crown, this crown is actually the Spikes of
SARS-CoV-2. This virus is spread by using the media of droplets that can
infect people if un-infected people is near the infected people. This virus can
enter into the body via ACE2 enzyme, which is the enzyme that converts ang-II
to ang(1-7) with its Spikes protein. Then the SARS-CoV-2 will infects the
body. Based on how the severe symptoms that caused by this virus are, there
are three parts. In the first week of infection is a milder symptoms, in the
second week the symptoms start to become severe and in the third week the
symptoms is in severe conditions. A patients with a severe Covid-19 most
likely has a severe pneunomia and maybe has ARDS at the third week of
infection, however the chances to get heart failures is rather lower. The
infection can be prevented by safety protocol and doing good lifestyle, such as
wear a mask, stay at home, managing sleep schedule, take vitamin C and etc.
There is a lot of researchs on the antiodies enhancement via therapy and the
development of vaccines and medicines to fighting the SARS-CoV-2, however
the vaccine yet to be discovered. Some people who has been infected by
SARS-CoV-2 are able to recover, the key of recover is high immunity level.
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