Differentiating Viral from Bacterial Infections
Differentiating Viral from Bacterial Infections
Estimates claim that over 1.2 million people died in 2019 as a direct result of an antibiotic-resistant bacterial infection. Statistics show that up to 4.95 million deaths in the same year were associated with antimicrobial resistance (AMR)1. The overuse and misuse of antibiotics is considered to be the largest contributing factor to the rise of AMR. Antibiotics are effective at treating a wide range of bacterial infections, however, when used to treat viral infections, they have little to no effect. Even still, many physicians continue to prescribe so-called empirical antibiotics as an all-encompassing treatment strategy. In their defence, differentiating viral from bacterial infections can be troublesome. Traditional testing takes the form of paired serology, which requires patients to visit a healthcare facility twice during a 2–4-week period. Many of these infections have distressing symptoms, making this an unreasonable time-to-diagnosis period. Novel molecular techniques can reduce the time to result in the determination of many infections. However, some of these methods are associated with high false positive rates and low specificity resulting in further misuse of antibiotics.
Mxyovirus resistance protein A (MxA) is a biomarker associated with viral infections. It displays antiviral activity against positive, double-stranded RNA viruses and some DNA viruses2. In a study from earlier this year, MxA was used to differentiate viral from bacterial infections in a cohort of 61 adults with an AUROC of 0.9 and a sensitivity and specificity of 92.3% and 84.6% respectively3. An additional study, known as the TREND study, found that a cut-off of 430μg/L could effectively differentiate bacterial and viral infections with an AUROC of 0.9, a sensitivity of 92% and a specificity of 100%4.
C-reactive protein (CRP) is a non-specific acute phase protein which is associated with bacterial infection. However, CRP levels have also been shown to be elevated in response to various viral infections such as Influenza virus, malaria5 and SARS-COV-26, limiting its utility in differentiating the aetiology of an infection.
Using both biomarkers in combination can help physicians determine the true aetiology of infection with high specificity, supporting antimicrobial stewardship and reducing the harmful use of these drugs. Available on the VeraSTAT, Randox provides tests for MxA and CRP, which together provide a fast and accurate method of detection and differentiation of bacterial and viral infections from a small sample.
We have provided an educational guide which describes these biomarkers and their usefulness in the arena of viral and bacterial detection. If you’re interested in learning more, you can find our educational guide here.
Differentiating Viral from Bacterial Infections
Alternatively, don’t hesitate to browse our range on our website or get in touch with one of our team at marketing@randox.com who will be happy to help with any query you have!
References
- Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022;399(10325):629-655. doi:10.1016/S0140-6736(21)02724-0
- Liao S, Gao S. MxA: a broadly acting effector of interferon-induced human innate immunity. Visualized Cancer Medicine. 2022;3:2. doi:10.1051/vcm/2022002
- Metz M, Gualdoni GA, Winkler HM, et al. MxA for differentiating viral and bacterial infections in adults: a prospective, exploratory study. Infection. Published online February 3, 2023. doi:10.1007/s15010-023-01986-0
- Rhedin S, Eklundh A, Ryd-Rinder M, et al. Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study. Clinical Microbiology and Infection. 2022;28(9):1251-1257. doi:10.1016/j.cmi.2022.05.008
- Joseph P, Godofsky E. Outpatient Antibiotic Stewardship: A Growing Frontier—Combining Myxovirus Resistance Protein A With Other Biomarkers to Improve Antibiotic Use. Open Forum Infect Dis. 2018;5(2). doi:10.1093/ofid/ofy024
- Paranga TG, Pavel-Tanasa M, Constantinescu D, et al. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Front Immunol. 2023;14. doi:10.3389/fimmu.2023.1213246
RX Imola: Inflammatory Biomarkers in COVID-19
Over the course of human history, few events have had such a dramatic impact as the COVID-19 pandemic. According to the World Health Organization (WHO), as of 12th July 2023, the SARS-CoV-2 virus has claimed almost 7 million lives and figures continue to rise1. While many who become infected are only subject to mild symptoms, those who develop a more severe form of the infection are encumbered with a debilitating flu-like condition, often requiring days, if not weeks of bed rest. In a paper from June 20232, the Rx Imola was used to study C reactive protein concentrations, along with other biomarkers, in mild and severe COVID-19 patients in order to develop novel risk stratification methods for this potentially life-threatening viral infection.
The impact on healthcare services around the world cannot be understated. In developed countries, access to services for both COVID-related and other conditions took a catastrophic hit. In low-to-middle-income countries, the impact has been even more distressing, all but eliminating basic medical care in favour of combating COVID-19, partly due to inferior resources and facilities3.
In times of medical emergency, it is crucial to have an efficient and effective means of stratifying the risk to patients and a process for suitably categorising those into the least and most at risk of severe complications or death. Due to the rate at which COVID-19 spread, unfortunately, the world lacked these mechanisms for SARS-CoV-2, resulting in mass hospital overpopulation, cancelled appointments for other life-threatening conditions and ultimately the staggering mortality statistics we’ve been bombarded with since January 2022. This prompted an unprecedented surge in medical research and major advances in testing capabilities, giving us new methods of detecting SARS-CoV-2 and determining the risk posed to individuals.
One such investigation, by Paranga et al., (2023) studied a total of 13 biomarkers to determine which could accurately differentiate mild, moderate, and severe cases and identify biomarkers which were good predictors of fatality2. C reactive protein (CRP) was the best-described biomarker relating to COVID-19 throughout the pandemic. This paper compares it to 12 other biomarkers including suPAR, sTREM-1, ferritin, MCP-1 and Lactate dehydrogenase. Of these, it was discovered that CRP was clearly the most effective biomarker for differentiating mild from severe cases, with concentrations in those with severe infection being, on average, 45% higher than in those with mild symptoms2. Additionally, the authors discovered that CRP levels were not significantly affected by age, a factor known to affect the inflammation and immune responses, providing a powerful and inclusive risk stratification tool. Some of the additional conclusions drawn from this paper can be seen below2:
- Lactate dehydrogenase, sTREM-1 and HGF were good predictors of mortality in COVID-19.
- suPAR was identified as a crucial molecule in characterising Delta variant infection and mortality.
- The initial values of inflammatory biomarkers were good to excellent predictors of disease severity in COVID-19 patients.
- Disease severity and mortality are associated with a higher rate of comorbidities including thrombocytopenia and other blood diseases, circulatory and respiratory system diseases and liver diseases such as cirrhosis.
So, what is CRP and how does it become elevated in response to a SARS-CoV-2 infection? CRP is a non-specific, acute-phase protein, meaning its concentration is altered in response to inflammation4. The acute respiratory distress syndrome induced by SARS-CoV-2 is, in part, a result of the hyperinflammation caused by the virus2. CRP is a well-characterised inflammatory biomarker and is therefore well-suited for identification and risk stratification in an emerging disease.
This investigation2 utilised the RX Imola, a rapid, comprehensive clinical chemistry platform, to quantify CRP. With the RX Imola, laboratories can gain access to the world’s largest clinical chemistry test menu covering routine chemistries as well as specific proteins, lipids, and more providing a cost-effective and user-friendly platform. With 60 cooled reagent positions and a sample carousel with 20 cooled positions for controls and calibrators, the RX Imola is an ideal solution for small to medium-throughput laboratories seeking an innovative and reliable clinical chemistry system. Randox also supplies suitable, high-quality reagents, and through Acusera, state-of-the-art controls and calibrators, completing the clinical chemistry portfolio.
References
1. World Health Organisation. WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/.
2. Paranga TG, Pavel-Tanasa M, Constantinescu D, et al. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Front Immunol. 2023;14. doi:10.3389/fimmu.2023.1213246
3. Jain P. Impact of COVID-19 Pandemic on Global Healthcare Systems and the role of a new era of global collaborations. Sushruta Journal of Health Policy & Opinion. 2021;14(3):1-5. doi:10.38192/14.3.2
4. Nehring S. C Reactive Protein . https://www.statpearls.com/articlelibrary/viewarticle/18744/.
CRP Assay
Reagent | C-Reactive Protein (CRP)
Powered by BiozC-Reactive Protein (CRP): The Most Sensitive Acute Phase Reactant
Benefits of the Randox Assay
Limited Interference
The Randox CRP assay has shown to have limited interference from conjugate and free bilirubin, haemoglobin, Intralipid® and triglycerides.
Liquid ready-to-use
The Randox CRP assay is available in a liquid ready-to-use format for convenience and ease-of-use.
Stable to expiry
The Randox CRP assay is stable to expiry when stored at +2oC to +8oC.
Applications available
Applications available detailing instrument-specific settings for the convenient use of the Randox CRP assay on a variety of clinical chemistry analysers.
Dedicated calibrator and controls available
Dedicated CRP calibrator and controls available offering a complete testing package.
Ordering Information
| Cat No | Size | ||||
|---|---|---|---|---|---|
| CP7950 | R1 7 x 20ml (L) R2 2 x 12ml | Enquire | Kit Insert Request | MSDS | Buy Online |
| CP9742 | R1 6 x 66ml (L) R2 6 x 13ml | Enquire | Kit Insert Request | MSDS | Buy Online |
| CP3826 | R1 6 x 20ml (L) R2 3 x 9ml | Enquire | Kit Insert Request | MSDS | Buy Online |
| (L) Indicates liquid option | |||||
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
More Information
C-reactive protein (CRP) is the dominant acute phase protein in mammals 1. Elevated levels of CRP are not disease specific but are synthesised, by hepatocytes, in response to pro-inflammatory cytokines during inflammatory and/or infectious processes 2, 3. The physiological function of CRP is the enhancement of cell-mediated immunity through the promotion of phagocytosis, accelerated chemotaxis and the activation of platelets 1.
Known as a biomarker of acute inflammation, many large-scale prospective studies demonstrate the association between CRP and chronic inflammation, including: cardiovascular disease (CVD), cerebrovascular accident (CVA) (ischaemic stroke), Alzheimer’s Disease, and age-related macular degeneration 2.
CRP is a major cardiovascular disease (CVD) risk factor. A CRP level of >10mg/l correlates with a >4% risk of developing a fatal CVD event in 10 years, including: myocardial infarction, peripheral arterial disease, stroke and sudden cardiac death. Inflammation is an integral part in the development and rapid progression of coronary heart disease (CHD) 4.
The coronary artery disease (CAD) process is characterised by increasing levels of inflammatory biomarkers. CRP is not only an excellent biomarker or mediator of atherosclerosis but is a strong independent marker in the prediction of adverse CV events, including: myocardial infarction, ischaemic stroke, and sudden cardiac death. CPR can be utilised as a clinical guide for the diagnosis, management and prognosis of CVD 5.
The development of a cerebrovascular accident (CVA) (stroke) is the result of longstanding vascular inflammation, thrombosis, plaque rupture and subsequent brain ischaemia or infarction. Elevated CRP levels is associated with the development of CVA 6.
High sensitivity CRP (hsCRP) plays an important role in the early diagnosis, prognosis, long and short death risk and prediction of etiological subtypes of stroke 7. Find out more about the Randox hsCRP assay.
Alzheimer’s disease (AD) is the most common form of dementia, accounting for 60-80% of dementia cases 7. CRP is believed to be involved in the pathophysiology of cerebral small vessel disease (CSVD) and neurodegeneration 8. CRP levels are associated with cognitive impairment 9. Inflammation should be considered as a target treatment, with the aim of delaying the progression of subclinical brain damage and cognitive decline 8. Midlife elevations in CRP are associated with an increased risk of developing AD. Patients with AD, CRP elevations continues to predict increased dementia severity suggestive of a possible pro-inflammatory endophenotype in AD 10.
In COVID-19 patients, CRP testing has proved to perform well in discriminating disease severity and predicting adverse outcomes 11. CRP levels positively correlates with lung lesions, reflecting disease severity, and should be considered a key indicator in disease monitoring (see fig. 1) 12.
CRP levels are associated with computed tomography (CT) scores and COVID-19 disease development, with CRP levels increasing in the initial stage of severe COVID-19, prior to the CT findings 13.
Elevated CRP levels have been identified in 86% of patients admitted to hospital. CRP measurements are useful in diagnosis, assessing prognosis and monitoring for clinical improvements or deterioration 14.
Fig. 1. Relation between CRP levels, clinical severity, and lung lesions 12
CRP Calibrator
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References
Inflammatory Biomarker Series: Rheumatoid Factor
What are inflammatory biomarkers?
The purpose of measuring an inflammatory biomarker is to detect inflammation, which can assist clinicians in the identification of a particular disease or provide a marker of treatment response. Inflammation, either chronic or acute, is the body’s immune response to protect against harmful stimuli such as damaged cells, irritants or pathogens.1 When inflammation occurs in the body, extra protein is released from the site of inflammation and circulates in the bloodstream.2 It is these proteins, or antibodies, which clinicians are testing for in the blood as they can indicate if inflammation is present.Like many inflammatory biomarkers, such as rheumatoid factor (RF), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), further tests will be required as testing for these tests alone does not provide a clearly defined diagnosis. However inflammatory biomarker tests can provide clinicians with a good indication of what may be wrong with a patient, which is why they are commonly tested for in a clinical setting.
What is Rheumatoid Factor?
Rheumatoid factor (RF) is an autoantibody which can target and damage healthy body tissue and in turn cause inflammatory symptoms.3 It is uncommon for this antibody to be present in healthy individuals, which is why it is a beneficial test to aid the diagnostic process. In particular, rheumatoid factor can be used as an inflammatory biomarker to assist in the diagnosis of rheumatoid arthritis (RA). However the rheumatoid factor antibody can also be present in healthy individuals or patients with systemic lupus erythematosus, liver cirrhosis, Sjögren’s Syndrome, Hepatitis and other conditions.4 If a test detects rheumatoid factor levels above 14 IU/ml, this is considered abnormally high.3
What is Rheumatoid Arthritis?
Rheumatoid arthritis is an autoimmune disease which attacks the lining tissue of joints, resulting in chronic inflammation. This disease commonly affects the hands, feet and wrists, with symptoms causing pain, fatigue and loss of bodily function and over time may even lead to multiple organ damage.5 Although diagnosis of rheumatoid arthritis requires a physical examination, testing for rheumatoid factor can be beneficial to assist in the diagnosis of this disease. Other blood tests that can be used to detect biomarkers associated with rheumatoid arthritis include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgA, IgG, IgM and anti-cyclic citrullinated peptide (anti-CCP).
For health professionals
Randox Laboratories offer a leading portfolio of diagnostic reagents which includes a test for rheumatoid factor, with applications available for a range of biochemistry analysers. With a measuring range of 6.72 – 104 lU/ml, this assay can comfortably detect levels outside the normal range. Randox offer a complete diagnostic package for the screening of rheumatoid factor with a range of kit sizes, controls and calibrators available. Other inflammatory biomarker tests available from Randox include CRP, High Sensitivity CRP, Full Range CRP, IgA, IgG and IgM.
References:
1. Nordqvist, C. Inflammation: Causes, Symptoms and Treatment. Medical News Today, https://goo.gl/rT4WS9 (accessed 16 January 2017)
2. Harding, M., Blood Tests to Detect Inflammation, Patient, 2015, https://goo.gl/F4OGrz, (accessed 16 January 2017)
3. Shiel, W. C., Rheumatoid Factor (RF), MedicineNet, 2016, https://goo.gl/XPA69u 2016 (accessed 16 January 2017)
4. Rheumatoid Arthritis Organisation, Rheumatoid Factor Test, Rheumatoid Arthritis Organisation, 2016, https://goo.gl/JujE5a
5. Gibofsky, A. Overview of Epidemiology, Pathophysiology and Diagnosis of Rheumatoid Arthritis. The American Journal of Managed Care. Vol.18, No.13. p.295-302, 2012
Inflammatory Biomarker Series: CRP
An inflammatory biomarker detects inflammation in the body. Inflammation is not just the immediate, short-term response of the body to an injury or infection. Inflammation within the body can be a long-term, chronic condition resulting in a number of health implications. In diagnostics, measurement of an inflammatory biomarker can not only detect acute inflammation but provide a marker of treatment response.
C-reactive protein (CRP) is an acute phase protein produced by the liver in response to inflammation, infection and tissue injury. CRP is a particularly beneficial inflammatory biomarker as it is detected much faster than other markers in the blood. Levels of CRP increase when inflammation occurs and therefore it can be a significant biomarker in a range of diseases, including the following.
Cardiovascular Disease
An increasing amount of research exists to suggest CRP is not only a useful, non-specific inflammatory biomarker, but it may have a direct influence on coronary heart disease and cardiac events1. Inflammation can occur when LDL cholesterol builds up in the artery walls causing atherosclerosis. Modifiable risk factors of atherosclerosis include smoking, diabetes, poor diet, high blood pressure and physical inactivity, all factors which subsequently increase the risk of heart attacks, ischemic stroke, peripheral artery disease and even vascular dementia2,3.
Studies have also shown that persistent low levels of CRP can contribute to a person developing CVD. Therefore using high sensitivity CRP as an inflammatory biomarker can detect low levels, helping to predict the likelihood of a patient developing CVD in the future.
Diabetes
Research suggests that inflammation in the body can influence the development of type 2 diabetes. With the ability to be managed through diet and exercise, type 2 diabetes is commonly associated with obesity. Research has shown that excess body fat can cause continuous chronic low-grade inflammation as a result of inflammatory cytokines and increased plasma levels of CRP. As a result, this chronic inflammation has the ability to cause insulin resistance leading to the development of type 2 diabetes4.
Rheumatoid Arthritis
A three year study which analysed the bone and joint health of 10,000 patient samples in India has found that inflammatory biomarkers, in particular CRP and ESR (Erythrocyte Sedimentation Rate) were raised in most of the samples compared to any other markers5. Although CRP is a non-specific inflammatory biomarker, it can be used alongside other tests, such as Rheumatoid Factor, to diagnose inflammatory joint diseases such as Rheumatoid Arthritis. Not only will CRP levels be higher due to chronic inflammation, but CRP levels can be monitored to assess levels of inflammation over time, allowing clinicians offer effective treatment.
Chronic Obstructive Pulmonary Disease (COPD)
COPD is a condition associated with inflammation of the lungs and airways. Studies have shown that measuring CRP levels is beneficial to detect exacerbations, when symptoms of COPD get suddenly worse and can last for several days. This is because CRP levels spike when exacerbations happen, causing lung function to deteriorate6.
Neonatal Bacterial Infections
CRP is one of the preferred and frequently used tests in neonatal units when diagnosing suspected bacterial infections, such as neonatal sepsis, in newborns who show signs on infection. Due to delayed synthesis during the inflammatory response, the sensitivity of CRP is lowest during early stages of infection. It is therefore critical that extremely low levels of CRP can be detected during diagnosis to distinguish whether symptoms are related to an infectious or non-infectious condition. This early detection then allows for rapid and appropriate neonatal treatment7.
Inflammatory Bowel Disease
Research suggests that using CRP as an inflammatory biomarker can help distinguish between Inflammatory Bowel Disorder (IBD) and Irritable Bowel Syndrome (IBS)8. Although IBD and IBS have some similarities in symptoms, IBD causes chronic inflammation, whereas IBS is a non-inflammatory condition. Therefore using CRP as a biomarker can allow clinicians to deliver a confident and accurate diagnosis.
For health professionals
Randox Laboratories manufacture a wide range routine and niche biochemistry reagents for use in both a research and clinical setting. With a wide measuring range, the Randox CRP assay will perform excellently to detect levels outside of the healthy range. Also available is a Full Range CRP assay particularly beneficial for use in a neonatal setting, and a High Sensitivity CRP assay, depending on your diagnostic requirements. For more information, please contact: reagents@randox.com
References:
- Shrivastava, A. K., Singh, H.V., Raizada, A. and Singh, S.K. C-reactive protein, inflammation and coronary heart disease. The Egyptian Heart Journal. 67, 89-97. (2015)
- American Heart Association. Inflammation and Heart Disease. Available from: https://goo.gl/d82Ynr (2016)
- Harvard Health Publications. What you eat can fuel or cool inflammation. Harvard Health Publications. Available from: https://goo.gl/e8m3El (2007)
- Zeyda, M. and Stulnig, T. M. Obesity, Inflammation, and Insulin Resistance – A Mini-Review. Gerontology 2009; 55:379-386 (2009)
- Mukherjeel, R. Bone and joint health are crucial aspect, usually ignored by Indians. The Times of India. Available from: https://goo.gl/qluzhI (2016)
- Anderson, G. P. COPD, asthma and C-reactive protein. European Respiratory Journal 2006; 27: 874-876. (2006)
- Hofer, N., Zacharias, E., Müller, W. and Resch, B. An update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks. Neonatology 2012; 102: 25-36 (2012)
- Silva, P. Two Specific Proteins Allow the Exclusion of IBD in Patients with Irritable Bowel Syndrome. IBD News Today. Available from: https://goo.gl/pxMP53 (2015)
