C-reactive protein in the evaluation of patients with respiratory symptoms before and during the COVID-19 pandemic

C-reactive protein gets its name from its ability to bind C-polysaccharides of the pneumococcal cell wall. SBR is produced by liver cells, its main function is to activate the body's immune responses, bind microorganisms and break down damaged tissues.

Determining the level of SBR is of important practical importance for determining the risk of developing heart and vascular diseases, complications after myocardial infarction or stroke. If in patients with coronary heart disease the indicator of this parameter is greatly exceeded, this fact should be considered as a factor of increased risk of developing restenosis during angioplasty, as well as complications after coronary artery bypass grafting.

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In the body of every person, regardless of age, the liver produces a special compound called C-reactive protein (CRP). It helps fight infections and is involved in the healing process of injuries. When a person is healthy, the content of this protein in the blood is minimal or tends to zero. But as soon as a pathology develops in the body or an injury occurs, its concentration increases sharply after just six hours.

The C-reactive protein test is most often used to detect low-grade inflammation or infection in children that is difficult to detect by other methods. When uncontrolled, such pathologies lead to serious complications and affect the cardiovascular system. Therefore, it is so important to do timely analysis, identify the disease and carry out adequate therapy.

Medicine / 7. Clinical medicine

Digtyarenko I.
Digun N. V., Sych N. V. , Chernikova N. F., Sasik S. I.
KP "Pavlograd Maternity Hospital" DOR"

Diagnostic value of determining C-reactive protein in newborns.

Infections are the leading cause of neonatal mortality worldwide. Newborns in all countries die from sepsis and pneumonia. The incidence of neonatal sepsis is a strong indicator of the importance of neonatal infections in a country or region. In Western Europe, North America and Australia - 6-9 cases per 1000 births; in Asia - 7.1 -38 per 1000 births. In Africa - 6.5-23 cases per 1000 births. The reason for the high infectious risk of newborns is the immaturity of the immune system. Diagnosis of all neonatal infections is carried out by synthesizing data from the medical history of the mother and child, clinical symptoms, results of laboratory tests and instrumental examinations. Clinical signs of neonatal sepsis are nonspecific and are also found in other neonatal diseases: respiratory distress syndrome, metabolic disorder, intracranial hemorrhage and others.

KP "Pavlograd Maternity Hospital" DOS" participates in the WHO project "Effective perinatal care and care", where standards for examining newborns at risk for bacterial sepsis have been developed.

Screening tests to confirm the presence of infection include:

1) Counting the number of leukocytes (less than 5000/mm3 or more than 20,000/mm3).

2). Leukocyte index: the ratio of immature neutrophils to the total number of cells is more than 0.2. 3). ESR more than 15 mm/hour. 4). Positive latex test result for C-reactive protein greater than 0.8 mg/dL.

The results of this screening test are considered positive if two or more of the above laboratory tests are abnormal.

C-reactive protein is one of the most specific “late” markers of bacterial infection. The level of C-reactive protein is determined over time after 12-24 hours. Single test results are not indicative. A series of negative C-reactive protein test results allows clinicians to strongly exclude the presence of neonatal infection and discontinue antibiotic therapy.

In the clinical diagnostic laboratory of the KP "Pavlograd Maternity Hospital" DOS (level of medical care - second), the study of the level of C-reactive protein is carried out by the diagnosticum "CRP - latex test", NPP "Filicit - Diagnostics", Dnepropetrovsk. According to the passport, normal levels of C-reactive protein are up to 6 mg/l. This is an inexpensive analysis, determination time is 10-15 minutes, the required amount of blood serum is 10-20 μl, does not require expensive equipment and can be used in any laboratory.

In clinical practice, determination of the level of acute phase protein is used quite widely, but in newborns the specifics of this indicator have not been sufficiently studied. The purpose of our study is to determine the diagnostic value of C-reactive protein in newborns with various pathological conditions. An analysis of the perinatal period of 14 newborns at risk for 2012 was carried out. Full-term newborns were examined - 11 children (1 - low birth weight), premature newborns - 3. Of these, 10 were boys and 4 were girls.

In all cases, pregnancy occurred with deviations from the norm: anemia, gestational edema, threat of miscarriage. Infectious history in the mother: - asymptomatic bacteriuria – (in 3 women); - acute respiratory diseases - (in 2 women); - fungal colpitis - (in 2 women); -increase in temperature during childbirth – (in 3 women); - anhydrous period of more than 18 hours – (1 woman).

Anamnesis data in newborns: - distress – (in 4 children); — increase in body temperature (in 1 child); - hyperbilirubinemia – (in 6 children).

C-reactive protein levels were elevated in the first 24 hours of life in all 11 newborns:

- up to 48 mg/l - in 4 newborns (4 boys);

- up to 24 mg/l - in 6 newborns (4 boys and 2 girls);

- up to 12 mg/l - in 4 newborns (2 boys and 2 girls).

The highest level of C-reactive protein was observed in children with a pronounced clinical picture of intrauterine infection.

Thus

1. Determination of C-reactive protein has a high diagnostic value in diagnosing infectious conditions in newborns and in assessing the quality of treatment.

2. The determination of C-reactive protein has an economic justification and practical accessibility at all levels of medical care.

3. The activity of C-reactive protein in newborn boys is 4 times greater than in girls, as noted by other authors who conducted similar studies.

Literature:

1. Shunko E. E., Hanes T. S., Laksha O. T. Perinatal sepsis Kyiv, 2001.

2. John Cloherty. Manual on neonatology, Kyiv, 2002.

3. Bondarenko N.P., Orlovska I.Yu. etc. Diagnostic value of C-reactive protein in neonatal practice / Child Health / No. 2 (23). 2010

Benefits of analysis

The CRP test is the most sensitive and fastest method for detecting inflammation or damage. Its level rises even before the child feels the first signs of illness.

The dynamics of CRP in the body corresponds to the stage of development of the pathological process. That is, the more active the infectious or autoimmune process in the body, the higher the protein content in the blood. Therefore, this indicator is also called acute phase protein. As inflammation decreases, so does CRP levels. This allows you to monitor the course of the disease and evaluate the effectiveness of the developed therapeutic regimen.

Another important indicator of acute inflammation in the body is the erythrocyte sedimentation rate (ESR). These indicators are often compared, and the analysis of CRP is considered more effective. This is due to the fact that reactive protein in a child’s blood increases earlier than ESR, and decreases faster. This allows you to observe a more current picture of the course of the disease and take appropriate measures in a timely manner.

Indications

A blood test for CRP is prescribed for children when:

• suspected infectious or inflammatory disease;
• carrying out antibacterial therapy and monitoring its effectiveness;
• there is a risk of developing cardiovascular pathologies;
• recovery and complications in the postoperative period;
• transplant operations and complications such as rejection;
• autoimmune pathologies;
• control and treatment of chronic inflammatory conditions.

Direct indications for laboratory testing

Doctors at our medical center in Mytishchi give a referral for the determination of C-reactive protein when:

• preventive examinations of workers of social institutions;
• comprehensive examination of people in the older age group;
• monitoring the condition of patients after heart surgery;
• monitoring the effectiveness of therapy for cardiovascular pathologies;
• monitoring the condition of patients who have undergone angioplasty;
• differential diagnosis of pathologies of inflammatory, viral, fungal and parasitic types;
• monitoring the course of the disease during antibacterial therapy, chronic diseases and relapses;
• assessing the level of likelihood of heart and vascular diseases in patients with diabetes;
• control of treatment of cardiovascular diseases with statins and aspirin.

Preparing for the examination

In order for an analysis to detect the level of CRP in the blood to show a reliable result, it is necessary to properly prepare the child for the test:

• stop taking painkillers and antipyretic non-steroidal anti-inflammatory drugs 1-2 weeks beforehand, after consulting with your doctor;
• 2-3 days before the analysis, remove heavy physical activity;
• the day before the test, remove fatty and fried foods from your diet;
• For 8-12 hours then study, do not eat or drink anything other than water.

The analysis cannot be taken after physiotherapeutic procedures, as well as ultrasound, rectal, x-ray examination, and fluorography.

SRP and antibacterial therapy: a paradigm shift?

The COVID-19 pandemic has forced the international community to reconsider recommendations for the diagnosis and management of respiratory infections. For example, the recommendations of the UK National Institute of Health [20] for primary care physicians on the management of patients with community-acquired pneumonia previously suggested determining the level of CRP for symptoms of lower respiratory tract infection, if after a clinical study the diagnosis of pneumonia was not established and it was unclear whether to prescribe an antibiotic to the patient or not. An antibiotic should not be prescribed if the CRP level was less than 20 mg/L, if the CRP level was 20–100 mg/L, a delayed antibiotic was recommended (a prescription was given for a subsequent antibiotic if symptoms worsened), and if the CRP level was above 100 mg/L, a antibiotic. During the COVID-19 pandemic, this guidance was withdrawn and is currently being revised [20]. The Russian medical community is also expecting updated recommendations, some of them have already been published in the form of drafts [8], others are under revision. Further studies will show whether, in the long term, the doctor's decision to prescribe antibiotic therapy for respiratory infection will depend on the results of the rapid test for CRP [2, 4, 21]. The introduction of such tests into the routine practice of primary care physicians should be considered in the context of initiatives for the rational use of antibiotic therapy.

The primary care physician also faces the question of which inflammatory biomarker is best to use and whether it is advisable to prescribe several tests simultaneously. In 2021, the results of a prospective cohort study of nearly 137,000 outpatients [22] who underwent biomarker testing (including CRP or ESR, or both) for various conditions (including infections) were published. CRP testing has been shown to have greater diagnostic accuracy for infections than ESR testing, and using both tests simultaneously only marginally increases diagnostic accuracy (which is clinically controversial and economically irrational). The authors suggested that CRP levels should be used as a first-line test in most cases (infections, autoimmune conditions, cancer).

What do deviations from the norm mean?

A doctor should interpret the results. Since there is no protein in the blood of a healthy child or its concentration is minimal, there is no need to talk about a reduced level. Exceeding the normal level of CRP in the blood of children as a result of the analysis may indicate:

• up to 30 mg/l – viral diseases, systemic rheumatic pathologies, malignant diseases;
• up to 100 mg/l – acute bacterial infections, exacerbation of chronic and rheumatic pathologies, tissue damage, including after operations;
• up to 300 mg/l – extensive burns, sepsis.

Deviations from the norm are not a diagnosis and require additional examination. Depending on the clinical picture and complaints of the child, treatment can be carried out by otolaryngologists, urologists, dentists, surgeons and other specialized doctors. To establish a diagnosis and develop a treatment plan, doctors prescribe additional instrumental and laboratory tests.

The role of CRP in the diagnosis of respiratory diseases

Russian professional communities developing clinical guidelines (which were mainly approved before 2020) include the determination of CRP level in the diagnostic standard and criteria for assessing the quality of medical care for a number of nosologies:

community-acquired pneumonia

(Russian Respiratory Society, 2021, project) [5]: it is recommended to study the level of CRP in the blood serum in all hospitalized patients, especially with an uncertain diagnosis of pneumonia (absence of inflammatory infiltration in patients with a characteristic history, complaints and local symptoms). At a concentration of more than 100 mg/l, the specificity of the test in confirming the diagnosis exceeds 90%, while at a concentration of less than 20 mg/l, pneumonia is considered unlikely. The level of CRP correlates with the severity of the disease, the prevalence of inflammatory infiltration and the prognosis of the disease. Determination of the level of CRP in the blood upon admission to the hospital, as well as a decrease in the level of CRP by more than 25% from the initial value at the time of discharge are criteria for the quality of specialized medical care for adults with pneumonia [5];

chronic obstructive pulmonary disease

(COPD) (Russian Respiratory Society, 2021) [6]: a study of CRP levels is recommended in patients with exacerbation of COPD to determine indications for antibacterial therapy (with CRP levels of 10 mg/l and above);

acute respiratory viral infection

in children (Union of Pediatricians of Russia, 2021 and 2021, project) [7, 8]: it is recommended to study the level of CRP in the blood serum to exclude severe bacterial infection in children at temperatures above 38 ° C, especially in the absence of a visible focus infections. It is emphasized that a CRP level above 30–40 mg/l is more typical for bacterial infections (diagnostic accuracy is more than 85%), however, even with an adenoviral infection, the CRP level can exceed 30 mg/l;

bronchitis

in children (Union of Pediatricians of Russia, 2021 and 2021, project) [8, 9]: indications for immediate testing of CRP levels (usually in a hospital setting) are fever over 39 °C with signs of intoxication, respiratory failure, suspicion of bacterial infection, in which an indicator of a bacterial infection is a CRP level of more than 30 mg/l;

pneumonia (community acquired)

in children (Union of Pediatricians of Russia, 2021, project) [8]: indications for studying the level of CRP are the same as for bronchitis. It is emphasized that with typical community-acquired pneumonia, the level of CRP reaches more than 30–59 mg/l; with atypical (mycoplasma, chlamydial) pneumonia, the increase in CRP is less pronounced. Studying the level of CRP when there is doubt about the diagnosis of pneumonia and determining its type in hospitalized children is included in the quality criteria for specialized medical care;

acute otitis media

(National Association of Otolaryngologists, 2021) [10]: CRP level determination in severe cases is indicated.

CRP as an indicator of bacterial infection

The critical levels and dynamics of changes in the concentration of CRP in community-acquired pneumonia were determined [11]. For example, with mild pneumonia, the level of CRP is 50–60 mg/l, moderate – 90–110 mg/l, severe – 130–150 mg/l. An unfavorable sign of a severe course and an indication for intensification of antibacterial and detoxification therapy is a CRP level above 150 mg/l. In pneumococcal and legionella pneumonia, in the first 32 hours of illness, the level of CRP can be 160–170 mg/l and 178–200 mg/l, respectively [11]. The ineffectiveness of treatment is indicated by a CRP concentration of more than 100 mg/l on the 4th day of antibiotic therapy, as well as a decrease in the CRP level by less than 60% of the initial level on the 3rd day and by less than 90% of the initial level on the 7th day of antibacterial therapy. therapy [11].

The accuracy of a diagnostic test as an indicator of bacterial infection increases when it is part of the clinical evaluation algorithm for a patient with a respiratory infection [1, 2, 12]. In the recommendations of the European Respiratory Society, published in 2011, the likelihood of a diagnosis of community-acquired pneumonia was proposed to be assessed by the level of CRP: below 20 mg/l with symptoms present for more than 24 hours - the diagnosis of pneumonia is extremely unlikely; more than 100 mg/l - the diagnosis of pneumonia is assessed as probable [13].

The ability to perform rapid testing of CRP levels directly during an appointment minimizes unnecessary antibiotic therapy and does not expose patients to the risk of potential side effects. This is especially true in conditions of limited time, as well as diagnostic uncertainty, when the symptoms of viral and bacterial infections are nonspecific. Thus, a Russian randomized trial of the use of a rapid test to determine CRP levels showed that general practitioners who used the test for acute cough and/or respiratory tract infections were 21.3% less likely to prescribe antibiotics compared to the control group (where the solution was the question of prescribing an antibiotic was made only on the basis of the clinical picture) [14].

CRP as a marker of inflammation in COVID-19

The study of CRP levels during the COVID-19 pandemic not only has not lost its relevance, but has also acquired additional significance. Monitoring of inflammatory markers, including CRP, as part of a biochemical blood test for confirmed COVID-19 is included in the national recommendations of many countries, including Russia [15–18]. Moreover, according to the UpToDate resource, the concentration of CRP associated with severe COVID-19 exceeds 100 mg/l (the normal value is less than 8 mg/l) [19].

Temporary guidelines “Prevention, diagnosis and treatment of the new coronavirus infection COVID-19” (version 11 dated 05/07/2021) characterize CRP as the main laboratory marker of process activity in the lungs [18]. An increase in CRP levels correlates with the extent of lung tissue damage and is the basis for initiating anti-inflammatory therapy. Determination of CRP concentration plays a role in the diagnosis and management of patients with COVID-19 and allows us to assess:

severity, prevalence of inflammatory infiltration and prognosis of outcome of pneumonia in COVID-19. The characteristics of the moderate course of COVID-19, along with clinical indicators, also include a CRP level of more than 10 mg/l; in addition, the concentration of CRP increases in most patients simultaneously with an increase in the content of interleukin (IL) 6 and ESR;

development of acute respiratory distress syndrome (ARDS). When it develops, along with other markers (IL-6, D-dimer, ferritin, fibrinogen, triglycerides, lactate dehydrogenase), it is recommended to determine the level of CRP every 48–72 hours until a stable negative value is obtained;

development of macrophage activation syndrome. An increasing level of CRP is a laboratory indicator of progressive macrophage activation syndrome (along with an increase in ferritin levels and the development of two-three-line cytopenia);

the development of cardiovascular complications in COVID-19 is accompanied, among other things, by an increase in the level of CRP;

laboratory monitoring of patients with COVID-19 includes determining the level of CRP for moderate cases no later than 24 hours after admission, then at least 2 times a week, for severe cases at least 1 time in 2 days;

indications for pathogenetic therapy. The level of CRP is included in the list of criteria that determine the indications for prescribing pathogenetic therapy for COVID-19. Other laboratory parameters include the number of leukocytes and lymphocytes, ferritin and IL-6 levels (not always available for routine diagnosis). The indication for prescribing Janus kinase inhibitors or an IL-17 inhibitor is an increase in the level of CRP within 3-6 norms, inhibitors or blockers of IL-6 - within 6-9 norms, for prescribing IL-6 receptor inhibitors or an IL-1β inhibitor level CRP should exceed 9 norms or increase 3 times on the 8th–14th day of the disease;

indications for discharge from hospital. One of the criteria for discharge from hospital to continue treatment on an outpatient basis (until the results of laboratory testing of biological material for the presence of SARS-CoV-2 RNA) is a CRP concentration of less than 10 mg/l [18].