C‑reactive Protein in Elderly and Pregnant COVID‑19

Abstract

Review Article
The clinical characteristics and prognosis of high‑risk groups, including elderly and pregnant women, may vary according to the overall
susceptibility of novel coronavirus. For that, numerous researchers worldwide have concentrated their efforts on finding a trustworthy biomarker
that can determine the severity, prognosis, and survival of those affected. C‑reactive protein (CRP), an inflammatory biomarker that showed
higher levels in coronavirus 2019 (COVID‑19) cases, underlay inflammation degree and was used to gauge the severity of COVID‑19. In this
review, we discuss whether CRP might have other uses in COVID‑19 cases besides predicting the severity and the clinical outcomes among
vulnerable risk groups. Doctors must analyze CRP levels along with the period of illness to identify those liable for rapid progress and be able
to categorize case severity to guide the clinical decision to improve prognosis.

Full text

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College of Medicine, Mustansiriyah University
Volume 21 • Issue 2 • July - December 2022
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114
Abstract
Review Article
intROductiOn
More than 420 million cases and about 5.9 million fatalities
have been reported since China reported the rst instances of
the coronavirus 2019 (COVID‑19).[1]
COVID‑19 infection can vary from asymptomatic to severe
type of respiratory distress. Regretfully, besides vaccination as
the most eective preventive approach added to social isolation
and wearing protective masks, there are just a few therapeutic
therapies available.[2]
Age was related to death in the initial report in hospitalized
Chinese patients, comparable to prior results from severe
acute respiratory distress (SARS) illness. Increased age was
an independent risk factor for death among older patients,
with odds risk about twice for ages between 65 and 79 years
as opposed to 50–64 years.[3,4]
Geriatrics are an important susceptible population to
coronavirus. Geriatric sensitivity to severe COVID‑19 is
due to age, which reduces immunity in several ways. Aging
promotes inammatory response to pathogens and decreases
the eectiveness of infection suppression. There was a clear
positive link between older ages and higher death rates.
Furthermore, many geriatrics have chronic conditions such
as diabetes and hypertension, making them more prone to
severe COVID‑19.[4,5]
Finally, several COVID‑19 therapeutic techniques are
ineective in elderly individuals.[6]
Understanding the warning signs of alarming COVID‑19 in
the elderly is critical for an eective and timely treatment
plan. As a result, many scientists worldwide have focused
their eorts on developing a reliable biomarker that can be
depended on in detecting the severity of this condition.[7]
C‑reactive protein (CRP) is a protein released by the liver
and the cornerstone of every inammatory response and a
crucial part of the innate immune process. CRPs are the body’s
initial pathogen line of defense. Although structurally dierent
from the immunoglobulin (Ig) molecule, CRP has functional
qualities with the Igs, such as the capacity to stimulate
The clinical characteristics and prognosis of high‑risk groups, including elderly and pregnant women, may vary according to the overall
susceptibility of novel coronavirus. For that, numerous researchers worldwide have concentrated their eorts on nding a trustworthy biomarker
that can determine the severity, prognosis, and survival of those aected. C‑reactive protein (CRP), an inammatory biomarker that showed
higher levels in coronavirus 2019 (COVID‑19) cases, underlay inammation degree and was used to gauge the severity of COVID‑19. In this
review, we discuss whether CRP might have other uses in COVID‑19 cases besides predicting the severity and the clinical outcomes among
vulnerable risk groups. Doctors must analyze CRP levels along with the period of illness to identify those liable for rapid progress and be able
to categorize case severity to guide the clinical decision to improve prognosis.
Keywords: C‑reactive protein, diagnostic, elderly, pregnant, prognostic, therapeutic
Address for correspondence: Dr. Wassan Nori,
Department of Obstetrics and Gynecology, College of Medicine,
Mustansiriyah University, Baghdad, Iraq.
E-mail: Dr.wassan76@uomustansiriyah.edu.iq
This is an open access journal, and arcles are distributed under the terms of the Creave
Commons Aribuon‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix,
tweak, and build upon the work non‑commercially, as long as appropriate credit is given and
the new creaons are licensed under the idencal terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
How to cite this article: Ali EA, Salman DA, Nori W. C‑reactive protein
in elderly and pregnant COVID‑19 cases: A new role for an old marker.
Mustansiriya Med J 2022;21:114‑8.
C‑reactive Protein in Elderly and Pregnant COVID‑19 Cases:
A New Role for an Old Marker
Eham Amer Ali1, Dina Akeel Salman2, Wassan Nori2
1Department of Chemistry and Biochemistry, College of Medicine, Mustansiriyah University, Baghdad, Iraq, 2Depar tment of Obstetrics and Gynecology, College of
Medicine, Mustansiriyah University, Baghdad, Iraq
Access this article online
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Website:
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DOI:
10.4103/mj.mj_54_22
Submitted: 30‑Oct‑2022 Revised: 24‑Nov‑2022 Accepted: 30‑Nov‑2022 Published: 02‑Jan‑2023

Ali, et al.: C‑reactive protein in COVID‑19
Mustansiriya Medical Journal ¦ Volume 21 ¦ Issue 2 ¦ July‑December 2022 115
agglutination, complement xation, inducing capsular swelling
in bacteria, and phagocytosis.[8]
Triggered by tissue damage or infection, CRP concentrations can
rapidly rise to more than 1000–3000 times higher than normal.
The standard value of CRP in the blood is >10 mg/L, but it rises
swiftly within 6–8 h and peaks 48 h after the illness begins.[7]
After stages of inammation are passed, the concentration of
CRP is down, and nally, the patient will recover. The severity
of many diseases is signicantly related to CRP. CRP synthesis
can be stimulated by a variety of inammatory mediators,
including interleukin‑6. Acute infection, a chronic inammatory
condition, and Type II metabolic disease have all previously
been connected to CRP.[9] Since its discovery, CRP has been
considered a checking instrument for inammation severity
and a diagnostic adjunct.[9,10]
Moreover, when CRP is released in plasma early, this enhances
the chance of plasma leakage. Consequently, the prediction of
severe bronchitis was detected by CRP.[11]
Biological markers such as CRP can be utilized to assess
and interpret clinical characteristics more precisely. Hence,
knowing the CRP level may be pivotal for the timely assessment
and appropriate treatment of COVID‑19 complications. CRP
estimation reects:
1. The existence and severity of the inammatory process
2. Allow distinction of inammatory from noninammatory
3. Treatment requirement
4. Assess prognosis and anticipate future risk.[12]
Furthermore, anti‑inflammatory or immunosuppressive
medicines have little eect on CRP levels unless they decrease
the activity of the underlying illness.[13]
For these reasons, it is critical to comprehend CRP and how
its level uctuates according to illness severity in distinct
categories. CRP is a disease biomarker for diagnosis,
prognosis, and risk assessment. In this review, we will
emphasize the role of CRP in high‑risk groups (elderly and
pregnant) to see if the inammatory marker remains at the
top of forecasting disease severity and explore other new
roles for this inammatory biomarker during the COVID‑19
pandemic.
A seveRity And pROgnOstic biOMARkeR AMOng the
eldeRly
Mehraeen et al. conducted a systemic review that discussed
risk factors for having a fatal outcome following COVID‑19.
Increasing age was one, and being a male was another risk
factor.
Higher CRP was associated with a 1.02 (0.96–1.08) odds ratio
for fatal outcomes.[12]
Brandao’s study compared the levels of CRP among patients
with cases of COVID‑19 pneumonia; its levels were
signicantly higher among deceased cases (P < 0.0001);
moreover, the levels were higher (P < 0.0001) among those
who were intubated and admitted to the intensive care
units (ICUs) compared with those who did not.[14]
Ali[15] discussed that higher serum CRP was seen in up to
two‑thirds of severe COVID‑19 patients. In addition, CRP
was signicantly greater in severally infected cases compared
to nonsevere cases, with a CRP level of 39.4 mg/L in severe
cases vs. 18.8 mg/L in mild cases.
CRP levels were higher in cases where the illness had
progressed to a severe stage. As a result, with a cuto value of
26.9 mg/L, it can be a valid prognostic marker upon hospital
admission. Furthermore, cases that ended in mortality had
ten times higher CRP levels than recovered patients (median:
100 vs. 9.6 mg/L). The authors stated that for every unit rise
in CRP concentration, there is an increased probability of
experiencing severe illness episodes by 5%.[15]
Wang et al.’s study[16] examined CRP’s role among dierent
age groups: young, middle aged, and elderly; its levels were
signicantly higher in severe cases and those admitted to
hospitals across all age groups. Geriatrics showed even
more elevated CRP, which was correlated in univariate and
multivariate analysis to severe forms of the infection; in
addition, CRP predicts severe illness in geriatrics with an
accuracy of 0.85.
Wang et al.[17] conducted a retrospective analysis that included
deceased COVID‑19 cases and compared their features to those
of surviving severe and critically sick cases in the COVID‑19
treatment facility. Enrolled cases had a median age of 71 years
and showed no specic demographic aspects among dead
patients compared to those surviving severe and critically
sick cases. Interestingly, male‑to‑female fatality rates were
comparable. However, various laboratory values, including
CRP, revealed signicant variations. COVID‑19‑deceased
patients showed greater levels of CRP and D‑dimer.
The exaggerated inflammatory response and cytokine
overproduction escalate CRP levels among severely infected
COVID‑19 cases. CRP levels increase when lung tissue
is damaged, and many organs fail to function due to the
overactivity of cytokines.[18]
To summarize, CRP can dierentiate severe cases or cases
with aggressive course following the primary infection.
Furthermore, CRP can predict the case mortality and be lower
among those who survived severe infection.
c‑ReActive pROtein As A fOllOw‑up biOMARkeR
Many acknowledge the immunological aspects of COVID‑19,
which results in what is known as the long COVID‑19
syndrome. The patients suered from nonspecic symptoms
such as shortness of breath, general weakness, memory
impairment, and loss of cognitive function: some reported
symptoms related to the digestive tract and other symptoms.
The disease may last several weeks or months following the

Ali, et al.: C‑reactive protein in COVID‑19
Mustansiriya Medical Journal ¦ Volume 21 ¦ Issue 2 ¦ July‑December 2022
116
acute infection and evolve over time. Its prevalence is based
on sex, age being higher among women and the elderly.[19]
Das and Verma[20] conducted a prospective study on elderly
patients after their acute infection recovery. The study recruited
90 cases aged over 60 years and subgrouped them according
to computerized tomography (CT) scanning nding into mild,
moderate, and severe cases.
They assessed the patients by CT and CRP levels. Their result
conrmed increased CRP values among severe cases, which
was linked to a higher score of high‑resolution CT, indicating
the valuable role of CRP in monitoring patient recovery.
tReAting seveRely ill cOvid‑19 cAses with
c‑ReActive pROtein ApheResis
Concerning the SARS‑CoV‑2 induced by COVID‑19, the CRP
plasma concentration was reported to be increased, analogous
to bacterial infections. In addition, CRP levels associate with
a poorer prognosis in COVID‑19 and have been shown to
be a valid marker for various detrimental events, such as the
necessity for mechanical ventilation. As a result, therapeutic
targeting CRP was proposed early in the epidemic.[21]
CRP apheresis is an extracorporeal treatment that specically
reduces CRP plasma levels with minimal adverse eects.[22]
As a result, CRP may now be addressed therapeutically and
selectively. Recently, it was suggested as a treatment for
severe SARS‑CoV‑2‑induced pneumonia.[23] Following the
publication of three case reports reporting individual healing
attempts (CRP apheresis in COVID).[24] The average age of
those patients was 62 years, and they all suered from medical
comorbidities. They were categorized as having a progressive
COVID‑19 course with failing lungs (the signs of severe lung
inltration in all cases) and a CRP >100. Depending on their
CRP levels, these individuals received repeated apheresis
procedures.[23]
Surprisingly, those patients improved with an 85% reduction of
their serum CRP; one out of seven cases passed away the rest
showed signs of improvement in the radiological assessment
of the lung.
The authors recommended that CRP apheresis be used as soon
as possible following the development of severe COVID‑19,
which we presume is during the rst 72 h. With a CRP level, the
cuto was more than 100 mg/L. Out of seven patients, six were
discharged well. Their result opened the way for therapeutic
targeting of CRP in the early stages of severe COVID‑19 with
no side eects and a case fatality of 14%, which dramatically
decreases for those high‑risk groups.[24]
c‑ReActive pROtein in pRegnAnt wOMen with
cOvid‑19
Pregnant women endure several physiological changes, the
most prominent of which are modications in immunity and
hormones that maintain the survival and growth of the baby.[25]
Pregnant women have a twofold increase in the
lung‑angiotensin‑converting enzyme‑2 receptor, an essential
step in viral entry and cell replication. COVID‑19 promotes
destruction, inammation, and bleeding in lung pneumocytes
via those receptors.[26]
Consequently, pregnant women are more susceptible to serious
illnesses; even women with nonsevere COVID‑19 are at risk
for severe pneumonia, mortality, admission to the ICU, and
oxygen support when compared to nonpregnant women. In
addition to other adverse pregnancy outcomes such as preterm
labor, particularly among cases with medical comorbidities
such as preeclampsia and diabetes.[27] There have been reports
of severe maternal morbidity and perinatal mortality due to
COVID‑19. According to evidence, pregnant women infected
with COVID‑19 may exhibit identical symptoms to the general
population.[28]
Infection severity and parity were substantially related to bad
obstetric and newborn outcomes; older age pregnant women
were more likely to suer moderate‑to‑severe infection than
those with asymptomatic or mild signs of the disease.[29]
The gestational age at which the infection occurred was also
inuential to the severity of the infection; case severity was
highest among cases in the third trimester. However, the eect
of parity was contradictory in some studies, and ethnicity was
not inuenced obstetric outcomes.[30]
In line with earlier reports among the general population,
higher CRP levels in seropositive mothers were signicant
parameters linked with the severity of the infection.[31]
One of the laboratory predictors of maternal mortality is CRP;
deceased mothers had increased CRP levels than those who
survived, indicating more severe infection and inammatory
reactions. Furthermore, they may reect an underlying cytokine
storm in COVID‑19, characterized by severe clinical features,
including acute respiratory distress syndrome, multiple organ
dysfunction syndromes, and maternal mortality.[32‑34]
Yamamoto et al. examined the prognostic value of higher CRP
and low platelet counts in assessing the need for inpatient
treatment alongside starting the medical intervention, including
O2 supply or the addition of systemic steroids or uid supply
owing to high‑grade temperature or a sequel of the infection.[30]
At a criterion of 1.280 mg/dl, CRP predicted pregnant women
that needed patient treatment with 81% sensitivity and 100%
specicity and a reliable area under the curve of 0.9. The
authors proposed a triage management treatment (weeks of
gestation; blood test results: CRP levels and platelet counts)
that will help risk categorization for seropositive cases during
a crisis to handle many cases and prioritize admission for
high‑risk groups based on the model proposed.[30]
Kim et al. examined the usefulness of CRP and ferritin
levels among seropositive cases admitted to the hospital
in a retrospective study design. The authors found that
CRP and serum ferritin are linked with adverse pregnancy
outcome (such as pneumonia and admission to ICU).

Ali, et al.: C‑reactive protein in COVID‑19
Mustansiriya Medical Journal ¦ Volume 21 ¦ Issue 2 ¦ July‑December 2022 117
Moreover, they conrm they are reliable predictors of poor
prognosis in COVID‑19‑seropositive mothers during the third
trimester.[35]
It is interesting that CRP and ferritin could predict poor
outcomes even if the pregnant symptoms were mild or if the
patient had an asymptomatic infection, which highlights its
role in guiding the design plan of treatment.[35‑37]
cOnclusiOn
CRP is a low‑cost, easy‑to‑measure predictive biomarker
that links COVID‑19 severity, progression of infection,
and predicted mortality upon hospital admission. It can
guide the clinical decision to prescribe medication and
follow COVID‑19 patients. It was implemented during the
rehabilitation of geriatric patients and was therapeutically
targeted in severely ill patients; as for pregnancy, it had
diagnostic, prognostic roles in addition to serving as a predictor
of adverse pregnancy outcomes.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
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