What is the false positive rate of the Monospot (Mononucleosis Spot Test) and can COVID-19 (Coronavirus Disease 2019) cause a false positive result?

False Positive Rate of Monospot Test and COVID-19 Relationship

The Monospot test has a false positive rate of approximately 4% in general testing scenarios, and while COVID-19 is not specifically documented to cause false positive Monospot results, other viral infections including cytomegalovirus (CMV) have been reported to cause false positive results.

Understanding the Monospot Test

The Monospot test (heterophile antibody test) is a rapid screening tool for infectious mononucleosis caused by Epstein-Barr virus (EBV). It works by detecting heterophile antibodies produced during EBV infection.

Test Performance Characteristics:

• Sensitivity: 70-92% (meaning 8-30% false negatives)
• Specificity: 96-100% (meaning 0-4% false positives) 1

False Positive Causes

The Monospot test can yield false positive results in several conditions:

• Viral hepatitis
• Cytomegalovirus (CMV) infection 2
• HIV infection
• Leukemia and lymphoma
• Pancreatic cancer
• Systemic lupus erythematosus
• Rubella
• Dengue fever 1

Notable Case Example:

A documented case shows a 75-year-old woman with acute CMV infection had a positive Monospot test despite negative EBV viral capsid antibody tests and negative EBV DNA PCR, confirming that CMV can cause false positive Monospot results 2.

COVID-19 and Monospot Testing

While there is no direct evidence in the provided literature specifically documenting COVID-19 as a cause of false positive Monospot tests, several considerations are important:

1. COVID-19 has been documented to occur as a coinfection with EBV 3
2. COVID-19 testing itself has high specificity (99-100%) with very low false positive rates 4
3. Other viral infections have been shown to cause false positive Monospot results

Clinical Implications:

When evaluating a positive Monospot test in a patient with COVID-19 symptoms or confirmed infection:

1. Consider the possibility of:

   • True EBV coinfection with COVID-19
   • False positive Monospot due to COVID-19 or other viral infection
   • Unrelated persistent false positive (documented to last for years in some cases) 5

2. Confirmatory testing should include:

   • EBV-specific serologies (VCA IgM, VCA IgG, EBNA)
   • EBV DNA PCR if available
   • COVID-19 testing if clinically indicated

Clinical Approach to Positive Monospot in COVID-19 Era

1. Evaluate clinical presentation:

   • Classic EBV symptoms (sore throat, lymphadenopathy, fatigue)
   • COVID-19 symptoms (respiratory symptoms, fever, loss of taste/smell)
   • Atypical lymphocytosis (present in both conditions)

2. Perform confirmatory testing:

   • EBV-specific serologies to confirm or rule out true EBV infection
   • COVID-19 testing as appropriate

3. Consider alternative diagnoses if both EBV and COVID-19 are negative:

   • CMV infection
   • Other viral infections
   • Non-infectious causes of false positive results

Key Pitfalls to Avoid

1. Don't assume a positive Monospot confirms EBV infection - up to 4% may be false positives
2. Don't dismiss the possibility of coinfection - EBV and COVID-19 can occur simultaneously
3. Don't neglect confirmatory testing - EBV-specific serologies are needed when clinical suspicion is high despite Monospot results
4. Don't forget that false positive Monospot tests can persist - some individuals show persistent false positives for years without clinical significance 5

In patients with atypical presentations or when treatment decisions depend on accurate diagnosis, specific EBV serologies should be performed regardless of Monospot results 6.