C-reactive protein (CRP) is a protein produced by the liver in response to inflammation. CRP levels in the blood can rise sharply within hours of an inflammatory stimulus and are therefore used as a marker of inflammation. Both bacterial and viral infections can cause elevated CRP levels, so an isolated high CRP alone cannot distinguish between the two. However, there are some general trends that can help determine if high CRP is more likely to indicate a bacterial or viral source.
Key Points
- CRP is an acute phase reactant produced by the liver that rises in response to inflammation.
- Both bacterial and viral infections can cause CRP levels to become elevated.
- In general, bacterial infections tend to cause higher CRP elevations than viral infections.
- However, there is significant overlap in CRP levels between bacterial and viral infections.
- Looking at the overall clinical picture is important to distinguish bacterial versus viral etiology.
CRP Physiology
CRP is synthesized by hepatocytes in response to inflammatory cytokines, particularly interleukin-6 (IL-6). In healthy individuals, baseline CRP levels are usually less than 10 mg/L. However, within 6 hours of an inflammatory stimulus, CRP levels can increase up to 1000-fold. The concentration of CRP directly correlates with the severity of inflammation or tissue injury. CRP levels peak at 36-50 hours after the initial stimulus and the plasma half-life is about 19 hours. Therefore, CRP is a useful marker for detecting inflammation and monitoring disease activity.
CRP Response to Infection
Both bacterial and viral infections can stimulate significant CRP elevations due to immune activation and release of inflammatory cytokines like IL-6. However, bacterial infections tend to cause higher CRP elevations compared to viral infections. For example, one study found median CRP levels of 159 mg/L in adults hospitalized with community-acquired pneumonia compared to only 42 mg/L in those with viral respiratory tract infections.
Some key points about CRP levels in different types of infections:
- Bacterial pneumonia – CRP typically >100 mg/L
- Viral pneumonia – CRP usually between 40-60 mg/L
- Severe bacterial sepsis – CRP usually >200 mg/L
- Viral infections like influenza – CRP
However, there is significant overlap between CRP levels in bacterial versus viral infections. For example, some patients with severe viral pneumonia can have CRP levels >200 mg/L, while mild bacterial infections may only cause slight CRP elevations.
Distinguishing Bacterial from Viral Infections
Given the overlap in CRP levels between bacterial and viral etiologies, CRP alone cannot definitively diagnose the source of infection. However, trends in CRP levels over time can sometimes help distinguish between bacterial and viral infections:
- Bacterial infections – CRP continues to rise if untreated
- Viral infections – CRP peaks within 1-3 days then gradually declines
Other inflammatory markers like procalcitonin may also be helpful. Procalcitonin levels are typically higher in bacterial infections compared to viral illnesses. Therefore checking both CRP and procalcitonin can help provide additional evidence to support a bacterial or viral etiology.
Ultimately, the full clinical picture must be considered including: symptoms, exam findings, imaging results, microbiological data, and response to treatment. This contextual information along with inflammatory markers like CRP are needed to determine if an elevated CRP is more likely related to a bacterial or viral source.
Common Causes of High CRP
Some common medical conditions that can cause high CRP levels include:
Bacterial Infections
- Pneumonia
- Sepsis
- Meningitis
- Osteomyelitis
- Pyelonephritis
- Cellulitis
- Peritonitis
Viral Infections
- Influenza
- COVID-19
- Viral pneumonia
- Mononucleosis
- Hepatitis
- Herpes infections
Other Causes
- Inflammatory arthritis (rheumatoid arthritis, lupus, vasculitis)
- Inflammatory bowel disease
- Kawasaki disease
- Myocardial infarction
- Malignancies like lymphoma
- Tissue necrosis
- Severe burns
- Surgery or trauma
Normal CRP Levels
Normal reference ranges for CRP:
| CRP Level | Interpretation |
|---|---|
| <1.0 mg/L | Normal |
| 1.0-3.0 mg/L | Mild inflammation |
| >3.0-10 mg/L | Active inflammation |
| >10 mg/L | Severe inflammation |
However, CRP levels should always be interpreted in the context of the clinical scenario. Even slight CRP elevations above the normal range may be significant in certain clinical situations like evaluating treatment response in inflammatory arthritis.
Limitations of CRP Testing
There are some important limitations of CRP testing to keep in mind:
- Nonspecific – Elevated in many inflammatory conditions, not just infections
- Moderate sensitivity – Normal levels do not always rule out infection
- Can be elevated due to non-infectious causes like trauma or malignancy
- Cannot differentiate between bacterial and viral infections
- Late normalization – Can take weeks to normalize after clinical recovery
Therefore, CRP should not be used in isolation to make definitive diagnoses. Instead, it is best used together with clinical evaluation and other lab markers like white blood cell count to support diagnostic and treatment decisions.
Conclusion
In summary, while both bacterial and viral infections can cause elevated CRP levels, bacterial infections tend to induce higher CRP elevations compared to viral illnesses. However, there is significant overlap between the two. Looking at CRP trends over time and in combination with other clinical information can help determine whether significantly high CRP is more likely related to a bacterial versus viral source. However, CRP alone cannot definitively distinguish between bacterial and viral etiologies. Ultimately, interpretation of CRP levels must be made within the full clinical context.