What is the interpretation and management of a positive or negative C19 (Coronavirus 19) Ag (Antigen) Test result in patients suspected of having COVID-19 (Coronavirus Disease 2019)?

From the Guidelines

A positive C19 Ag test result in a symptomatic patient should be interpreted as a confirmed COVID-19 infection, while a negative result should be confirmed with a standard NAAT if clinical suspicion remains. The Infectious Diseases Society of America (IDSA) guidelines suggest using standard NAAT over rapid Ag tests for symptomatic patients due to higher sensitivity, but Ag tests can be used if results will be delayed more than 1 day 1. The sensitivity of Ag tests is higher when performed within 5 days of symptom onset, with a pooled sensitivity of 89% (95% CI: 83% to 93%) and specificity of 100% (95% CI: 99% to 100%) in this timeframe 1.

Key Considerations for C19 Ag Test Interpretation

• Symptomatic patients: A positive Ag test result confirms COVID-19 infection, and isolation should be initiated for at least 5 days from symptom onset, with continued masking for 5 additional days when around others.
• Asymptomatic individuals: A positive Ag test result also confirms infection, and isolation should begin from the test date.
• Negative Ag test results: These should not be used to rule out infection in symptomatic patients, especially early in infection, and should be confirmed with PCR testing or repeated antigen testing 24-48 hours later if COVID-19 is still suspected.
• Antigen test characteristics: They detect viral proteins, work best when viral load is high (typically 1-5 days after symptom onset), provide rapid results (15-30 minutes), but are less sensitive than PCR tests.

Management Based on Test Results

• Treatment decisions: For high-risk patients, including those eligible for antivirals like Paxlovid or Molnupiravir, treatment should be initiated promptly within 5 days of symptom onset based on positive test results, following appropriate clinical evaluation for contraindications and drug interactions.
• Isolation and masking: Symptomatic patients should remain isolated until fever-free for 24 hours without medication and symptoms are improving, with continued masking for 5 additional days when around others.

Given the high specificity of Ag tests, a positive test result does not require routine confirmation, but the lower sensitivity, especially early in infection or in asymptomatic individuals, necessitates careful interpretation and potential confirmation with standard NAAT in clinically suspected cases 1.

From the Research

Interpretation of C19 Ag Test Results

• A positive C19 Ag (Antigen) Test result indicates the presence of SARS-CoV-2 antigens in the sample, suggesting an active COVID-19 infection 2.
• A negative C19 Ag Test result does not necessarily rule out COVID-19, as the test may have low sensitivity, especially in early stages of infection or in asymptomatic individuals 3, 2.
• The sensitivity of antigen tests can range from 16.7 to 85%, which may lead to false-negative results 3.
• A positive predictive value of 97.7% and a negative predictive value of 95.2% suggest that a positive RAT result is a reliable indicator of COVID-19, but negative results may need to be confirmed through additional testing, such as RT-PCR 2.

Management of Patients with Positive or Negative C19 Ag Test Results

• Patients with a positive C19 Ag Test result should be managed as COVID-19 cases, with appropriate isolation, treatment, and monitoring 4, 5.
• Patients with a negative C19 Ag Test result but high clinical suspicion of COVID-19 should undergo further testing, such as RT-PCR, and be managed accordingly 3, 2.
• The use of imaging modalities, such as chest X-ray or CT scans, may be helpful in diagnosing and managing COVID-19, especially in patients with severe symptoms or those who are at high risk of complications 4, 5.
• The choice of diagnostic test and management approach should be based on individual patient factors, such as symptom severity, underlying health conditions, and exposure history 6, 2.

Diagnostic Approaches for COVID-19

• Reverse transcriptase polymerase chain reaction (RT-PCR) is considered the gold standard for diagnosing COVID-19, but it may have limitations, such as false negatives and the need for specialized equipment 3, 2, 5.
• Antigen tests, such as rapid antigen tests (RATs), can be useful for rapid diagnosis, but their sensitivity and specificity may vary 3, 2.
• Imaging modalities, such as chest X-ray and CT scans, can be helpful in diagnosing and managing COVID-19, but their use should be balanced against the risks of radiation exposure and transmission 4, 5.