Does fecal or serum calprotectin increase during a common cold (viral upper respiratory infection)?

Does Calprotectin Rise During a Common Cold?

Yes, calprotectin (both serum and fecal) can rise during viral respiratory infections, including the common cold, though the elevation is typically less pronounced than in bacterial infections.

Evidence from Viral Respiratory Infections

The most direct evidence comes from studies examining calprotectin in various respiratory infections:

Serum/Circulating Calprotectin

• Serum calprotectin is elevated in viral respiratory infections compared to healthy controls, though significantly less than in bacterial infections 1
• In COVID-19 (a viral respiratory infection), serum calprotectin levels were markedly elevated (median 3500 ng/mL vs. 1060 ng/mL in controls) 2
• Circulating calprotectin increases in SARS-CoV-2 infection with plasma levels >131.3 ng/mL showing discriminatory ability for infection 3

Fecal Calprotectin

• Fecal calprotectin also rises in viral infections, with COVID-19 patients showing median levels of 124.3 µg/g versus 25.0 µg/g in controls 2
• This elevation occurs even in patients without gastrointestinal symptoms 2, 4

Clinical Implications and Important Caveats

Distinguishing Bacterial from Viral Infections

The key clinical point is that calprotectin rises in both bacterial AND viral infections, but the magnitude differs:

• Calprotectin was significantly higher in bacterial pneumonia, mycoplasma pneumonia, and streptococcal tonsillitis compared to viral respiratory infections 1
• The overall clinical performance of calprotectin in distinguishing bacterial from viral respiratory infections was superior to procalcitonin (PCT) and heparin-binding protein (HBP) 1

Specificity Concerns

Critical caveat: The AGA guidelines explicitly note that "CRP, fecal calprotectin, and fecal lactoferrin may be elevated because of nonintestinal sources of infection or inflammation" 5. This means:

• If you're using fecal calprotectin to monitor inflammatory bowel disease (IBD), a concurrent viral upper respiratory infection (common cold) could falsely elevate the result
• This could lead to misinterpretation as IBD flare when the patient actually just has a cold
• The guidelines recommend testing for enteric pathogens when biomarkers are elevated with symptoms, but don't specifically address systemic viral infections 5

Practical Guidance

When interpreting calprotectin results:

1. Consider timing: If a patient has concurrent cold symptoms, defer non-urgent calprotectin testing until recovery (typically 1-2 weeks)
2. Repeat testing: If elevated calprotectin is found during a viral illness, repeat measurement 3-6 months later or after symptom resolution 5
3. Clinical context matters: The elevation from a simple cold is likely modest compared to severe bacterial infections or active IBD, but could still confound interpretation in borderline cases

Magnitude of Effect

While the studies don't specifically isolate "common cold" (rhinovirus, coronavirus, etc.) from more severe viral infections like COVID-19 or influenza, the data suggest:

• Any viral respiratory infection can elevate calprotectin above baseline
• The elevation is generally less than bacterial infections
• Both serum and fecal compartments are affected

Bottom line: A common cold can indeed raise calprotectin levels, making it a potential confounder when using this biomarker for other diagnostic purposes, particularly in IBD monitoring.