Sys Rev Pharm 2021;12(1):1114-1118

A multifaceted review journal in the field of pharmacy

Analysis of C - Reactive Protein (CRP) Conditions as a Corruption

Predictor of Coronavirus Disease 2019
Suci Iriani1*, Aripa Amril2, Irda Handayani3, Uleng Bahrun4
1PPDS Clinical Pathology, Faculty of Medicine, Hasanuddin University, Makassar
2Department of Clinical Pathology, Faculty of Medicine, Hasanuddin University, Makassar
3Installation of the Clinical Pathology Laboratory of the Sayang Rakyat Hospital, Makassar
4Installation of Clinical Pathology Laboratory Dr. Wahidin Sudirohusodo, Makassar

Corresponding Authors: Suci Iriani Email: ariesa_friendz@yahoo.com

ABSTRACT
This study was to analyze CRP levels as a predictor of COVID-19 severity by using Keywords: COVID-19, CRP, predictor, inflammatory markers
medical record data for COVID-19 patients who underwent treatment for the May-
August 2020 period at Sayang Rakyat Hospital, Makassar. The severity level was Correspondence:
classified as mild, moderate, and severe illness based on the Guidelines for the Suci Iriani
Prevention and Control of COVID-19 by the Indonesian Ministry of Health. CRP PPDS Clinical Pathology, Faculty of Medicine, Hasanuddin University, Makassar
levels were analyzed in all three groups. There were 162 patients consisting of 73 Email: ariesa_friendz@yahoo.com
mild illness, 44 moderate illness, and 45 seriously ill people. The Kruskal Wallis test
shows there was a significant difference in CRP levels in the three patient groups,
the highest was in the seriously ill group (p <0.001). The posthoc test showed that
the CRP level in the moderately ill group was also significantly higher than the mild
disease group, but lower than the severely ill group (p <0.001). The ROC curve
analysis shows the CRP level with the cut-off value≥10.0 mg / L in moderate pain
(sensitivity 81.8%; specificity 43.8%, PPV 46.8%; NPV 80.0%) and ≥58.0 mg / L in
severe illness (sensitivity 93.3%; specificity 81.2%, PPV 65.5%; NPV 96.9%). CRP
levels increase significantly in response to injury, infection, and inflammation in
severe disease. This shows that CRP is an inflammatory factor that plays an
important role in worsening COVID-19. CRP can predict COVID-19 patient
progression to moderate pain at a cut-off value ≥10 mg / L (sensitivity 81.8%,
specificity 43.8%) and towards severe illness at the cut-off value≥58 mg / L
(sensitivity 93.3%, specificity 81.2%).

INTRODUCTION with mild illness can be given symptomatic treatment,

Coronavirus Disease 2019 (Covid-19) is an infectious
disease caused by Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2). Common signs and
symptoms of Covid-19 infection include acute respiratory
symptoms such as fever, cough and shortness of breath.
The average incubation period is 5-6 days with the longest
incubation period of 14 days. Severe cases of Covid-19 can
cause acute respiratory syndrome and even death [1]. The
majority of patients with mild symptoms do not require
hospitalization, unless there are concerns about the
possibility of rapid worsening and with medical
considerations. Patients should undergo an isolation for at
least ten days from the appearance of symptoms and three
days symptom-free of fever and respiratory disorders.
The increase in the number of Covid-19 cases is happening
quite rapidly and has spread to various countries in a short
time. As of 17 October 2020, the World Health
Organization (WHO) reported 38,789,204 confirmed cases
with 1,095,097 deaths worldwide (Case Fatality Rate /
CFR 3.3%). The first case was reported in Indonesia on
March 2, 2020, then increased and spread rapidly
throughout Indonesia. As of October 17, 2020, there were
349,160 confirmed cases of Covid-19 with 12,268 deaths
(CFR 3.38%), while in Makassar the death rate reached
256 cases [2,3].
Clinical studies show that changes in the levels of several
laboratory parameters have an effect on the mortality rate
for Covid-19 patients. One of them is C - reactive protein
(CRP) which is considered an important marker that
changes significantly in Covid-19 patients. C - reactive
protein is a type of protein produced by the liver, which is
an early marker of infection and inflammation, making it a
useful marker for monitoring disease severity [4]. Patients
such as antipyretic administration if they have a fever.
Therefore, management for moderately ill patients is the
administration of symptomatic therapy for existing
symptoms and monitoring functions, implemented until
the symptoms disappear and the patient meets the criteria
to be discharged from the hospital.
Severely ill patients are generally treated in the intensive
care unit, while patients with mild illness are treated in
hospital isolation wards. One of the main problems in
handling Covid-19 is that some Covid-19 patients with
minor illnesses develop severe disease and even lead to
death. Therefore, it is important to identify early so that
therapy can be given that can prevent the patient from
becoming severe and even death.4
A research conducted by Gao Y et al (China) showed that
COVID-19 patients with severe illness had a mean CRP
level of 39.4 mg / L and mild illness 18.8 mg / L. A similar
study conducted by Mo P et al (China) stated that the mean
CRP level was significantly higher in severely ill patients
(46 mg / L) compared to those with mild disease (23 mg /
L).5, 6
To the researchers' knowledge, this study was the first to
report on CRP parameters on the severity of COVID-19
patients in Makassar. Based on this background,
researchers were interested in analyzing whether CRP as
a predictor of the severity of Covid-19 patients at RSUD
Sayang Rakyat Makassar, which was one of the referral
hospitals for Covid-19 in South Sulawesi Province since
May 2020.
MATERIALS AND METHODS
This retrospective study used medical record data of
patients diagnosed with Covid-19 who underwent

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 Iriani et al. /Analysis of C - Reactive Protein (CRP) Conditions as a Corruption Predictor of Coronavirus Disease 2019

treatment at the Hospital Sayang Rakyat Makassar,
conducted during the period May-August 2020. The study
samples were all populations that had data on the results
of CRP levels.
The diagnosis of Covid-19 is confirmed by means of
examination methods Real Time-Polymerase Chain
Reaction (RT-PCR) using nasopharyngeal and oro-
pharyngeal swab samples and detected SARS-CoV-2
ribonucleic acid (RNA) and examined CRP levels with the
fluorescence immunoassay (FIA) method.
The severity of Covid-19 was classified based on the 5th
Revision of the Guidelines for the Prevention and Control
of Covid-19 by the Ministry of Health of the Republic of
Indonesia (Ministry of Health), which was a minor illness
when accompanied by non-specific symptoms such as
fever, cough, sore throat, nasal congestion, malaise, muscle
pain, moderate pain when accompanied by fever, cough,
dyspnoea, rapid breathing, and severe pain if there was a
fever or under surveillance for respiratory tract infection,
plus one of the respiratory rate> 30 bpm, severe
respiratory distress, or oxygen saturation <90% .
Data analysis was performed using statistical software
using descriptive statistical calculations, frequency
distribution and Kruskal-Wallis statistical tests. The test
result was significant if p <0.05. Data were also analyzed
using the Receiver Operating Characteristics (ROC) curve
to assess the accuracy of the CRP in predicting the severity
of Covid-19. Therefore, this study did not compare CRP
with other parameters.
The approval of ethical eligibility was obtained from the
Health Research Ethics Commission (KEPK) Hasanuddin
University Medical Faculty Hasanuddin University
Hospital - Dr. Wahidin Sudirohusodo Makassar.
RESULTS
A total of 162 patients diagnosed with COVID-19 were
taken as study samples with ages ranging from 21-79
years, the most in the 50-59 years age group (34.6%).
Based on gender, most of the subjects studied were male,
and the most common comorbid found were Diabetes
Mellitus (DM) and hypertension. Thirty patients died and
132 recovered (Table 1).

Table 1: Characteristics of the research sample

Characteristics n (%)

Age (years)
<30 12 7.4
30-39 23 14.2
40-49 38 23.5
50-59 56 34.6
≥60 33 20.4

Gender

Male 86 53.1

Women 76 46.9

Comorbid
Hypertension 32 19.75
Diabetes mellitus 43 26.54
Coronary heart disease 2 1.23
Chronic Kidney Disease 1 0.62
Pulmonary TB 1 0.62
Bronchial Asthma 1 0.62
Severity
Mild pain 73 45
Moderate pain 44 27
Very sick 45 28
Output
Healed 132 81.48
Died 30 18.52
Source: Secondary Data

In this study, the average overall CRP level was 70.14 ± test showed that there was a significant difference in the
79.01 mg / L, with the highest mean CRP level in the mean CRP levels between the two groups (p <0.001)
seriously ill group (166.97 ± 73.39) and the lowest in the (Figure 1).
mild disease group (21.57). ± 21.07). The Kruskal-Wallis

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 Iriani et al. /Analysis of C - Reactive Protein (CRP) Conditions as a Corruption Predictor of Coronavirus Disease 2019

Figure 1: Comparison of CRP levels according to severity

The follow-up analysis (Posthoc test) of the Bonferroni
method showed that the CRP level in the moderately ill
group (51.69 ± 54.35 mg / L) was also significantly higher
than the mild disease group, but lower than the seriously
ill group (p <0.001) (Figure 1).
To predict each Covid-19 severity using the CRP
parameter, a value was determined cut-off using curves
ROC.

Figure 2: The ROC curve

Based on the analysis of the ROC curve, the CRP cut-off
value ≥10 mg / L can predict moderate illness COVID-19
with a sensitivity of 81.8%, specificity of 43.8%, Positive
Predictive Value (PPV) 46.8%, Negative Predictive Value
(NPV) 80.0%; and Area Under Curve (AUC) 0.665 (95%
Confidence Interval [CI] 0.557 - 0.774, p <0.01) (Figure
2a). This analysis also shows the CRP cut-off value≥58 mg
/ L can predict severe illness with a sensitivity of 93.3%,
specificity 81.2%, PPV 65.5%, NPV 96.9% and AUC 0.942
(95% CI 0.901 - 0.982 p <0.001) (Figure 2b).
DISCUSSION
The basic characteristics of this study indicated that more
patients were male (53.1%) than female (46.9%), and
most patients were aged 50-59 years. In line with research
conducted by Yiping Wei et al (China), it was reported that
the most sexes of Covid-19 patients were male (56.2%),
most were aged 50-65 years. The findings regarding more
male patients affected by Covid-19 were also confirmed by
Dong Ji et al (China). This is because the male sex hormone
suppresses the immune response, whereas the female
hormone estrogen provides a natural protective effect
against infection [7, 8, 9].
The results of this study indicate that the more severe the
patient's symptoms, the higher the CRP level in the blood
tends to be. A total of 45% of patients had mild illness, 27%
moderate illness, and 28% had severe illness with mean
CRP levels of 21.57 mg / L, 51.69 mg / L, and 166.97 mg /
L, respectively. The difference in CRP levels in the three
groups was statistically significant (p <0.001). This is in

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 Iriani et al. /Analysis of C - Reactive Protein (CRP) Conditions as a Corruption Predictor of Coronavirus Disease 2019
line with the retrospective cohort study of Fang Liu et al
(China) as well as the study by Ruan et al (China), namely
that the increase in CRP levels was significantly higher in
severe illness than in mild illness, indicating that
inflammatory factors play an important role in the
development of mild disease until weight [10, 11].
This study shows that CRP can be a predictor of the
severity of Covid-19 patients with mild, moderate, or
severe illness. At the CRP cut-off value≥10 mg / L can
predict moderate illness Covid-19 (sensitivity 81.8% and
specificity 43.8%) and it is more accurate to predict severe
illness Covid-19 at the CRP cut-off value≥58 mg / L
(sensitivity 93.3% and specificity 81.2%). In line with
research by Luo et al (China) it is shown that the CRP cut-
off value≥41.3 mg / L (sensitivity 65.0%, specificity 83.7%,
PPV 81.6%, NPV 68.2%) was associated with severe illness
in Covid-19 patients. Research by Chen et al (China) also
confirms the results of this study, that with a CT scan of the
chest in the form of ground glass opacity (GGO), CRP levels
will increase significantly 11.46 times in moderate pain
and 23.40 times in severe illness (p. <0.05). The AUC value
in the study was 0.898 (95% CI 0.835, 0.962, p <0.001).
This indicates that the higher the CRP level indicates the
more severe the severity of Covid-19 [12, 13].
C-reactive protein (CRP) is an acute phase protein that can
increase up to a hundred times in infection or
inflammation. When inflammation occurs, the body
experiences a natural and adaptive immune response that
causes many types of cytokines to be produced, including
pro-inflammatory cytokines such as tumor necrosis factor
alpha (TNF α) and interleukin 6 (IL-6). In Covid-19, these
cytokines will cause the hepatocytes in the liver to secrete
more CRP.Pro-inflammatory cytokines will affect the
hypothalamus, causing fever. These cytokines will also
cause vasodilation and increase in vascular permeability
resulting in a buildup of fluid in the lungs, which ultimately
interferes with breathing. These cytokines can also cause
multiple organ failure. CRP levels in the blood have been
studied in many previous cases for infectious diseases
because they have been found to increase significantly in
response to injury, infection, and inflammation. The ability
of CRP to be a marker of acute inflammation is
independent of demographic factors such as age, gender,
and baseline physical condition [14, 15, 16].
A meta-analysis study by Zeng et al (China) has also been
carried out on 16 studies regarding the relationship of
inflammatory markers to clinical manifestations of Covid-
19, covering a total of 3962 patients. This study confirmed
the findings of this study, that the group of patients with
mild disease had significantly lower levels of CRP than the
group with severe illness (p <0.001). Research by Wang et
al (China) also added that CRP levels were positively
associated with chest CT scan findings, namely the
diameter of the lesions in the lungs, as well as the
percentage of disease weight (correlation coefficient
0.873; 0.734; p <0.001). For high severe Covid-19 patients,
immediate oxygen supplementation therapy is given to
severe ISPA patients and patients with respiratory
distress, hypoxemia, or shock. Oxygen therapy begins with
the administration of 5 L/minute with nasal cannula and
titration to achieve the target of SpO2 ≥90%. There is a
necessary to monitor patients with worsening clinical
symptoms, such as respiratory failure, sepsis and perform
supportive treatment interventions as quickly as possible.
This study strengthens the possibility of using CRP to
predict the subsequent worsening of the patient's clinical
condition [16, 17].
1117 Systematic Reviews in Pharmacy
A limitation of this study is that age and comorbid factors
may have an effect on elevated CRP levels other than SARS-
COV-2 infection itself.
CONCLUSION
C-Reactive Protein can predict COVID-19 patients towards
moderate pain at the cut-off value ≥10 mg / L (sensitivity
81.8%, specificity 43.8%) and towards severe illness at the
cut-off value≥58 mg / L (sensitivity 93.3%, specificity
81.2%). This study also confirm that the treatment
procedures and actions of Covid-19 patients have been in
accordance with clinical indication, so that an early
detection of clinical manifestation will provide sufficient
opportunities for the proper application of management.
Finally, further studies with a larger sample size are
recommended, using additional markers and radiological
findings.
ACKNOWLEDGEMENT
The authors would like to express their gratitude to the
respondents (subjects) of this research for their readiness
to be interviewed and studied.
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