Can a person test positive for Covid-19 (Coronavirus disease 2019) via a PCR (Polymerase Chain Reaction) test and negative via a rapid antigen test?

COVID-19 PCR Positive with Negative Rapid Antigen Test: Understanding the Discrepancy

Yes, it is possible for a person to test positive for COVID-19 via PCR test while testing negative on a rapid antigen test. This discrepancy is well-documented and occurs due to fundamental differences in test sensitivity and the biological markers each test detects 1.

Why This Discrepancy Occurs

Test Sensitivity Differences

• PCR Tests: Detect viral RNA and are highly sensitive, capable of detecting even small amounts of viral genetic material
• Antigen Tests: Detect viral proteins (primarily nucleocapsid) and require higher viral loads to produce a positive result 1

Key Factors Contributing to Discrepancy:

1. Timing of Infection

   • Early infection: PCR may detect virus before antigen tests can
   • Late infection: PCR may detect non-infectious viral RNA fragments while antigen tests become negative 1

2. Viral Load Considerations

   • PCR can detect as little as a few viral RNA copies
   • Antigen tests typically require thousands of viral particles to register positive 1, 2

3. Clinical Status

   • Symptomatic patients: Antigen tests show 91.0% sensitivity for detecting replication-competent virus 3
   • Asymptomatic patients: Antigen tests show only 63.6% sensitivity for detecting replication-competent virus 3

Clinical Implications

When to Trust Which Test

• Positive PCR with negative antigen test: Likely indicates either early infection, late infection, or low viral load 1, 4
• Positive antigen test: High specificity (98.73%) means this is likely a true positive and indicates probable contagiousness 2, 5

Testing Recommendations Based on IDSA Guidelines

1. For symptomatic individuals:

   • Standard NAAT (PCR) is preferred over rapid antigen testing 1
   • If PCR results will be delayed >1 day, use antigen testing 1
   • For optimal antigen test performance, test within 5 days of symptom onset 1

2. If antigen test is negative but COVID-19 suspicion remains high:

   • Confirm with PCR testing 1
   • Consider repeating antigen testing if PCR is unavailable 1

Correlation with Infectiousness

• A negative antigen test correlates well with lack of culturable virus (99.9% negative predictive value for contagiousness) 2
• Positive antigen tests in symptomatic individuals strongly correlate with presence of replication-competent virus 3
• PCR cycle threshold (CT) values below 18.1 best predict contagiousness 2

Common Pitfalls to Avoid

1. Assuming a negative antigen test rules out COVID-19

   • False negatives are common, especially in asymptomatic individuals or early/late infection 1
   • If clinical suspicion is moderate/high, confirm negative antigen results with PCR 1

2. Relying solely on PCR for determining contagiousness

   • PCR can remain positive for weeks after infection, beyond the period of contagiousness 1
   • Antigen tests may better correlate with actual infectiousness 2, 3

3. Improper specimen collection

   • Poor sampling technique can lead to false negatives with both test types 6
   • Deep nasopharyngeal specimens may yield better results than superficial swabs 6

In summary, the discrepancy between PCR and antigen test results is a common occurrence that reflects the different technologies and detection thresholds of these tests rather than a failure of either test type.