JRSSEM 2021, Vol. 02, No. 4, 632 – 642
E-ISSN: 2807 - 6311, P-ISSN: 2807 - 6494
DOI : 10.36418/jrssem.v2i04.339 https://jrssem.publikasiindonesia.id/index.php/jrssem/index
OVERVIEW OF THE VALUE OF C-REACTIVE PROTEIN
AGAINST THE INCIDENCE OF SARS-CoV-2 disease
Maghfira Darma Burhani
Piksi Ganesha Polytechnic, Bandung, Indonesia
*
e-mail: maghfiradarmaburhani@gmail.com
*Correspondence: maghfiradarmaburhani@gmail.com
Submitted
: 06
th
November 2022
Revised
: 17
th
November 2022
Accepted
: 25
th
November 2022
Abstract: Coronavirus disease 2019 (COVID-19) is a disease caused by Severe Acute Respiratory
Syndrome Coronavirus 2 or SARS-CoV-2. Symptoms caused by the corona virus include mild to
severe and serious respiratory tract infections. C-Reactive Protein is one of the acute phase proteins
synthesized in the liver to monitor disease both non-specifically and systemically. C-Reactive
protein examination can detect acute phase inflammation which can be used to predict the
presence of inflammation in patients. The purpose of this study was to determine the results of the
examination of C-Reactive Protein Levels of patients suspecting SARS-CoV-19.This research is a
descriptive research with purposive sampling technique. The sample size in this study was 30
samples. This research was conducted at the Humana Peima Hospital from March to May 2022. The
research data were analyzed descriptively. Based on the results of the research that has been carried
out, it can be seen that the patients suspected of SARS-CoV-19 with positive CRP results were 24
patients with a percentage of 80% and negative CRP results as many as 6 patients with a percentage
of 20%. .
Keywords: SARS-CoV-2, C-Reactive Protein, Inflammation.
633 | C-Reactive Protein Value Overview Towards Event Disease Sars-Cov-2
INTRODUCTION
The SARS-CoV-2 virus or corona virus
is an RNA (ribonucleic acid) virus that has a
crown (corona) and can infect humans and
animals. The symptoms caused by this virus
are mild to severe and serious respiratory
infections. Coronavirus disease 2019
(COVID-19) is a disease caused by Severe
Acute Respiratory Syndrome Coronavirus 2
or SARS- CoV-2.
Laboratory examinations take an
important role in handling COVID-19
(Aryati, MS.2020). Starting from diagnosis,
therapy monitoring, prognosis to
surveillance. Abnormalities in laboratory
results are strongly influenced by the
clinical manifestations of a person infected
by COVID-19 according to the established
degree. (Rosdiana, etc al,2020). A literature
analysis revealed that hematological
abnormalities can predict mortality in
COVID-19 patients (Am J Hematol. 2020).
C-Reactive Protein (CRP) is known to
be the most sensitive inflammatory
indicator. C-Reactive Protein (CRP) is one of
the acute phase proteins synthesized in the
liver to monitor the disease non-specifically
or systemically. C-Reactive Protein (CRP) is
a protein produced by the liver organ in
response to inflammation in the body
found in the blood. C-Reactive Protein
(CRP) levels will increase in response to
infection, trauma, bacteria, injury or
inflammation. CRP is used as a prognostic
marker for inflammation. Imflamation is the
body's immune response to certain
diseases. Increased CRP levels are
associated with tobacco use, increased
body mass index, age, hypertension, insulin
resistance, diabetes, chronic kidney disease,
decreased left ventricular function, and
depression (Dewi, etc al. 2016).
The increase in C-Reactive Protein
(CRP) levels in Covid-19 patients is caused
by cytokine storms related to damage to
body tissues. Increased levels of C-Reactive
Protein (CRP) protein in COVID-19 patients
can cause a decrease in oxygen saturation,
venous thrombosis in pulmonary
embolism, acute kidney injury, and death.
The purpose of this study was to
determine the value of C-Ractive Protein
against the Incidence of Sars-Cov-2
Disease.
Coronavirus is a single-strained,
capsulated and non-segmented RNA virus.
Coronavirus belongs to the order
Nidovirales, family Coronaviridae.
Coronavirus has a much higher potential
for infectivity so that it spreads throughout
the world quickly, causing a global
pandemic (In Gennaro, 2020).
COVID-19 disease is caused by a new
type of Coronavirus named SARS-CoV-2.
The COVID-19 outbreak was first detected
in Wuhan City, Hubei Province, China in
December 2019. Patient zero who is
suspected to be the mastermind of this
pandemic is a 57-year-old woman selling
shrimp at Huanan Seafood Wholesale
Market, Wuhan named Wei Guixiang.
Originally, on December 10, 2019, she felt
feverish and unwell. He checked into the
nearest clinic. However, after checking
himself, he went back to selling. That's
when SARS-CoV-2 spread. On January 30,
2020, the WHO (World Health
Organization) declared a global health
emergency caused by SARS-CoV-2.
Because the progression of this disease is
accelerating and the number of patients
Maghfira Duty Burhani | 634
exposed is increasing, since March 11,
2020, by WHO this global health
emergency has been designated as a
pandemic (Qin, etc al. 2020).
Coronavirus has capsules, particles of
spherical or elliptical shape, often
pleimorphic with a diameter of about 50-
200m. The structure of coronavirus forms a
cube-like structure with the S protein
located on the surface of the virus This S
protein plays a role in the attachment and
entry of the virus into the host cell (Jin, et
al. 2020).
Coronaviruses are sensitive to heat
and can effectively be inactivated by
chlorine-containing disinfectants, lipid
solvents with a temperature of 56°C for 30
minutes, ethers, alcohols, perioxyacetic
acid, non-ionic detergents, formalin,
oxidizing agents andoform chlorine. (Wang,
etc al. 2020). risk factors for COVID-19
include age, gender, history of disease,
nosocomial infections from patients and
hospital staff, history of smoking, use of
personal protective equipment.
Coronavirus is called zoonotic virus,
which is a virus that is transmitted from
animals to humans (Huang, et al. 2020).
Coronavirus in bats is the main source for
the incidence of Severe Acute Respiratory
Syndrome (SARS). In general, the flow of
Coronavirus from animals to humans and
from humans to humans through contact
transmission, droplet transmission, fecal
and oral routes (Wang, etc al. 2020). SARS-
CoV-2 is transmitted primarily through
respiratory, contact, and potentially fecal-
oral droplets. The life cycle of the virus on
its host occurs through 5 stages:
attachment, penetration, biosynthesis,
maturation and release. . Coronaviruses
consist of four protein structures: Spike (S),
membrane (M), envelope (E) and
nucleocapsid (N) (Sohrabi, etc al. 2020).
The incubation period for COVID-19
is between 3-14 days. Characterized by a
slightly decreased level of leukocytes and
lymphocytes, the onset of tightness,
decreased lymphocytes and worsening of
lesions in the lungs. If this phase is not
resolved, Acute Respiratory Distress
Syndrome (ARSD) may occur (Gennaro, etc
al. 2020). SARS- CoV-2 infection is
characterized by rapid viral replication and
late production of IFNs, mainly by dendritic
cells, macrophages, and respiration
epithelial cells followed by elevated levels
of proinflammatory cytokines called
cytokine storms. A cytokine storm is an
event of excessive inflammatory reaction in
which there is a rapid and large production
of cytokines in response to an infection.
This rapid pro-inflammatory triggers
inflammatory infiltration by the lung tissue
causing lung damage (Zhang, etc al. 2020).
C-Reactive protein is one of the acute
phase proteins found in normal serum even
in very small amounts (Kalma, 2018). CRP
levels increase after the presence of trauma,
bacterial infections, and inflammation. As a
biomarker, CRP is considered an acute
phase inflammatory response that is easy
and inexpensive to measure compared to
other inflammatory markers. CRP is also
used as a prognostic marker for
inflammation (Dewi, etc al. 2016). CRP is an
alpha-globulin produced in hepar and its
levels will increase greatly in inflammatory
processes and tissue damage. CRP is a
sensitive inflammatory indicator, which
increases up to 1,000 times after
inflammation and quickly drops when the
635 | C-Reactive Protein Value Overview Towards Event Disease Sars-Cov-2
inflammation has subsided (Olson, 2014).
CRP is an acute phase protein
Pentraxin, a calcium-binding protein with
immunological defense properties. The
CRP molecule consists of 5-6 identical non-
glycocylic polypeptide subunits, consists of
206 amino acid residues, and binds to each
other non-covalently, forming one disc-
shaped molecule with a molecular weight
of 110 – 140 kDa, each unit has a molecular
weight of 23 kDa. W. Saunders (2003).
Based on the theory of intra-arterial
inflammation states that when
inflammation occurs, cytokines are
generated, one of which is Intraleukin-6 (IL-
6). Intraleukin-6 stimulates hepatocytes to
produce CRP (Agustin, 2016). The
inflammatory response in the form of
activation of macrophages and T
lymphocytes releases pro-inflammatory
mediators including TNF-α, IL-1 and IL-6
produced by macrophages in endothelial
wounds. This cytokine will stimulate the
formation of acute phase reactants, C-
reactive protein (CRP) in the liver. the
determinant of the concentration of CRP in
the circulation is to calculate the synthesis
of IL-6 thus describing directly the intensity
of the pathological process that stimulates
the production of CRP (Silalahi, 2013).
C-Reactive Protein is present in 2
forms, namely the pentamer form (pCRP)
produced by hepatocyte cells as an acute
phase reaction in response to infection,
inflammation and tissue damage and the
monomer (Mcrp) comes from the
dissociated CRP pentamer and may also be
produced by extrahepatic cells such as
smooth muscle arterial walls, adipose tissue
and macrophages (Silalahi, 2013).
The function and role of CRP is that it
can bind C-polysaccharides (CPS) from
various bacteria through precipitation/ag
reactions, can increase the activity and
motility of phagocyte cells such as
granulocytes and monocytes/macrop, has
selective binding power to T lymphocytes,
can bind and detoxicate endogenous toxin
materials formed as a result of tissue
damage (Silalahi, 2013).
CRP normally circulates at low stinger
concentrations, but in inflammatory
processes, infections or injuries to tissues
can lead to increased synthesis of CRP in
the liver. So it is important to conduct a CRP
examination (Agustin, 2016). In the CRP
examination, several methods are used,
including the Agglutination method, the
Sandwich Elisa method, the c. High
Sensitivity C-Reactive Protein (Hs-CRP)
method, the colorymetry method, the
Immunoturbidimetric method.
MATERIALS AND METHODS
The method used in this study is an
analytical descriptive method using a
crossectional study approach, which is a
study conducted on a set of objects that
aims to see a picture of a phenomenon
(including health) that occurs in a certain
population (Notoatmodjo, 2018) that uses
dependent variables and independent
variables. The dependent variable is the
examination of C-reactive protein levels.
Meanwhile, the independent variable is
suspect Sars-Cov-2. The research was
conducted at Humana Prima Hospital
Bandung, from March to May 2022. The
population of this sample is suspected
SARS-CoV-2 prolanis patients at Humana
Maghfira Duty Burhani | 636
Prima Hospital Bandung. The sampling
technique used is purposive sampling,
which is a sampling technique using
selected criteria. The type of data collected
is by using primary data.
The research population is the entire
object of study or object under study
(Notoatmodjo, 2018). The sample
population in this study was suspected
SARS-CoV-2 patients at Humana Prima
Hospital Bandung. The total population in
this study was 43 people calculated from
the average hospitalized patients
suspected of SARS-CoV-2 who met the
criteria for 3 months starting from March
2022 to May 2022.
The sample is a portion of the overall
population studied and is considered
representative of the population (Noor,
2017). The sample used in this study was a
lender from the nose for rapid antigen and
EDTA blood examination for the C-Reactive
Protein examination of the research
subjects carried out at Humana Prima
Hospital Bandung. In order to obtain a
representative sample of the population,
every subject in the population is sought to
have an equal chance of becoming a
sample.
As for the formulation used to
measure samples, the Slovin method is
used in Husein Umar (2010: 146), namely
the sample size which is a comparison of
the population with the presentation of the
looseness of inaccuracy. In this sampling, an
error tolerance level of 10% was used and
in determining the sample measurements
(n) and population (N) that have been
determined as follows:
N= Total Population
N= Number of Samples
e2= Error rate in selecting members of
the sample that the population N = 43
people with the assumption of error rate (e)
= 10%. Then the number of samples that
should be used in this study is as many as
n = N/(1+N(e)^2 )= 43/(1+43(0.1)^2 ) =
30.06 rounded to 30 samples.
So from the calculation results above,
to find out the sample size with an error
rate of 10% is 30 patients who are
suspected of SARS-CoV-2 at Humana Prima
Hospital Bandung. This study uses primary
data as a data source and primary data
form as a research instrument. The primary
data used by the researchers is in the form
of data on the results of the rapid antigen
examination and the C-reactive Protein
examination in COVID-19 patients at
Humana Prima Hospital. The data analysis
steps used are editing, coding, entering
data, tabulation.
This study used the technique of
Descriptive Statistical Analysis. Descriptive
Statistical Analysis is statistics that
discusses ways to summarize, present, and
describe data with the aim of being easy to
understand and have more meaning
(Dahlan, 2015). The data obtained from the
results of the CRP level examination will be
recorded and encoded then made in the
form of a table and calculated the
frequency distribution in the form of %
using the SPSS 23.0 program.
Tools and materials
Upperbio-tech tools, rapid test
antigen sets, alcohol swabs, plasters,
tourniquets, laboratory coats, detector
buffers, blood collector capillaries, cassette
tests, handscoons, micropipettes,
stopwatches, tissues, syringes, EDTA tubes.
637 | C-Reactive Protein Value Overview Towards Event Disease Sars-Cov-2
Principles of SARS- CoV-2 examination
The SARS-CoV-2 antigen rapid test is
a lateral flow immunoassay based on the
principle of the double antibody sandwich
technique. SARS-CoV-2 nucleocapsid
monoclonal antibody proteins conjugated
with color microparticles were used as
detectors and sprayed on conjugation
pads. During testing, the SARS-CoV-2
antigen in the specimen interacts with
SARS-CoV-2 antibodies conjugated with
color microparticles creating a complex
labeled antigen-antibody. This complex
migrates on the membrane through
capillary action up to the test line, where it
will be captured by the precoated
monoclonal antibodies of the SARS-CoV-2
nucleocapsid protein. The colored test line
will not be visible in the results window if
the SARS-CoV-2 antigen is present in the
specimen. the absence of a T line indicates
a negative result. control line C is used for
procedural control, and should always
appear if the test procedure is performed
correctly.
Principle of examination of C-
Reactive Protein
The test kit has the principle of
colorimetry containing a membrane coated
with anti-CRP specific monoclonal
antibodies. when that sample is mixed with
gold conjugate, the CRP molecule binds to
the antibody-gold conjugate. After the
dissolved sample is applied to the test
device. CRP molecules are captured by
immobile ants on the membrane, in the tpe
sandwich reaction. Unbound conjugates
are removed from the membrane with a
washing solution. The paper layer under the
membrane absorbs excess liquid. in the
presence of a pathological lever CRP, the
mebrane appears reddish with a color
intensity proportional to the concentration
of CRP. The q-pad reader measures the
intensity of the colors.. The measured color
intensity was measured quantitatively using
Upperbio-tech with a normal value of less
than 10mg/L.
RESULTS AND DISCUSSION
The following data from the study are
described in the table as follows:
Table 1. Research Results
No.
Sample
Code
Age
Rapid
Antigen
Test
Results
CRP
results
(mg/L)
1.
A1
3 Yrs
1 Mo
Positive
101.1
2
A2
65 yrs
5 mo
Positive
26.5
3.
A3
35 yrs
1 mo
Positive
10.4
4.
A4
41 Yrs
1 Mo
Positive
23.5
5.
A5
64 yrs
6 mo
Positive
12.0
6.
A6
64 Yrs
5 Mo
Positive
14
7.
A7
64 Yrs
2 Mo
Positive
75
8.
A8
52 yrs
7 mo
Positive
26.4
9.
A9
7 Yrs
10
Mo
Positive
50
10.
A10
67 yrs
9 mo
Positive
40
11.
A11
46 yrs
Positive
25.4
Maghfira Duty Burhani | 638
4 mo
12.
A12
64 Yrs
5 Mo
Positive
23.1
13.
A13
0 Yrs
10
Mo
Positive
11.1
14.
A14
63 yrs
9 mo
Positive
3.1
15.
A15
52 Yrs
4 Mo
Positive
54.2
16.
A16
72 yrs
8 mo
Positive
43
17.
A17
33 Yrs
9 Mo
Positive
11
18.
A18
29 Yrs
11
Mo
Positive
13.2
19.
A19
58 Yrs
1 Mo
Positive
12
20.
A20
33 Yrs
6 Mo
Positive
29
21.
A21
18 Yrs
6 Mo
Positive
13
22.
A22
7 Yrs
6 Mo
Positive
25
23.
A23
69 yrs
6 mo
Positive
15
24.
A24
0 Yrs
0 Mo
19 Hr
Positive
18.5
25.
A25
59 Yrs
1 Mo
Positive
16.3
26.
A26
58 yrs
71
mo
Positive
1.2
27.
A27
0 Yrs
1 Mo
Positive
3.0
28.
A28
33 Yrs
9 Mo
Positive
1.00
29.
A29
5 Yrs
Positive
0.8
5 Mo
30.
A30
0 Yrs
10
Mo
Positive
0.80
Table 2. Normal Value of Examination
Probe Parameters
Normal
Values
Rapid Test Antigen
Negative
CRP
< 10 mg/L
Table 3. Distribution of Proportion of CRP
Results in Whole Blood of SARS-Cov-2
Confirmed Patients
Table 4. Distribution of Proportion of CRP
Results by Age in SARS-Cov-2 Confirmed
Patients
Frequ
ency
Perc
ent
Vali
d
Perc
Cumul
ative
Percen
20%
80%
Distribusi Proporsi Hasil CRP Pada
Whole Blood Pasien Terkonfirmasi
SARS-Cov-2
Valid Negatif
Valid Positif
Frequ
ency
Perc
ent
Valid
Perc
ent
Cumul
ative
Percen
t
Va
lid
Nega
tive
6
20
20
20
Positi
ve
24
80
80
100
Total
30
100
100
639 | C-Reactive Protein Value Overview Towards Event Disease Sars-Cov-2
ent
t
Val
id
<
11
Ye
ars
7
23.3
23.3
23.3
11
-
20
Ye
ars
1
3.3
3.3
26.7
21
-
30
Ye
ars
1
3.3
3.3
30.0
31
-
40
Ye
ars
4
13.3
13.3
43.3
41
-
50
Ye
ars
2
6.7
6.7
50.0
51
-
60
Ye
ars
6
20.0
20.0
70.0
61
-
70
Ye
ars
8
26.7
26.7
96.7
71
-
80
1
3.3
3.3
100
Ye
ars
Tot
al
30
100
100
Based on the results of a study
conducted by researchers at the Humana
Prima Hospital Laboratory Bandung on 30
confirmed SARS-CoV-2 patients from
March to May 2022 with Positive CRP
results of 24 patients with a percentage of
80% and Negative CRP results of 6 patients
with a percentage of 20%. Most of the
sample of patients aged 61-70 years was 8
patients with a percentage of 26.7%. In old
age, there are physiological changes
related to aging, subjugation of immune
function and multimorbidity, namely
having more serious diseases and
complications, causing that age group to
be more susceptible to infection and at risk
of suffering from COVID-19 to the risk of
death (WHO, 2020).
The SARS-CoV-2 virus in sars-CoV-2
confirmed patients is associated with
increased inflammation in humans. C-
Reactive Protein (CRP) is an inflammatory
marker synthesized in the liver to non-
specific local and systemic diseases. The
< 11
Tahun
23%
11-20
Tahun
3%
21-30
Tahun
3%
31-40
Tahun
14%
41-50
Tahun
7%
51-60
Tahun
20%
61-70
Tahun
27%
71-80
Tahun
3%
Distribusi Proporsi Hasil CRP
Berdasarkan Usia Pada Pasien
Terkonfirmasi SARS-Cov-2
Maghfira Duty Burhani | 640
increase in CRP levels in patients with
confirmed SARS-CoV-2 is caused by an
inflammatory response arising from severe
infection from the SARS-CoV-2 virus. The
positive results in CRP are caused by
enlarged adipocyte tissue and the body will
produce a lot of protein in the body. When
adipocytes produce a lot of protein here
the body will experience inflammation or
inflammation (Situmeang, 2018).
Basic changes or dysfunctions that
occur in the endothelium of blood vessels,
vascular smooth muscle cells and
mesangial cells of the kidneys all cause
changes in cell growth and survival, which
will then lead to chronic inflammation.
Elevated CRP levels in patients with
complications found in the study subjects
can have an effect on the results of the
study. From the results of the study, it can
be concluded that the positive CRP results
in SARS-CoV-2 confirmed patients are
more than the negative CRP results. This is
because the patient experiences
inflammation or inflammation that occurs
in the body due to the SARS-CoV-2 virus.
And negative results can be caused
because the CRP level has decreased
because the sufferer is doing drug therapy,
a healthy lifestyle and it can also be due to
factors that are less sensitive in detecting
CRP.
CONCLUSIONS
Based on the research that has been
carried out, it can be concluded that there
are 24 confirmed SARS-CoV-2 patients with
Positive CRP results with a percentage of
80% and 6 negative CRP results with a
percentage of 20%. The positive CRP result
is caused by the patient experiencing
inflammation or inflammation in the body
due to the SARS-CoV-2 virus. Negative CRP
results are caused by patients doing drug
therapy, a healthy lifestyle and can also be
due to less sensitive tools in detecting CRP.
Based on the research above, the
advice that can be conveyed in this study is
that in sampling for the C-Reactive Protein
examination, it must be considered
correctly and clearly to determine the
anticoagulants that are in accordance with
the tools and reagents used, making the C-
Reactive Protein examination one of the
important examination items in the therapy
of SARS-CoV-2 confirmed patients, not
delaying the work of the C-Reactive Protein
examination after obtaining a sample
examination, and do not miss
communication with the patient in order to
obtain complete information about the
patient's condition when undergoing the
examination. It is necessary to carry out
further examinations to find out the
specifications of the inflammation that
occurs, it is necessary to know the
condition of the condition that can affect
the results of the examination.
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