Antigen test sensitivity: 60% (antigen) vs 90% (PCR)
- Antigen test / rapid, at-home test sensitivity could be as low as 60%, even in symptomatic cases
- At-home test should be performed two-times over three days
- PCR increases accuracy, results might be obtained as soon as a few hours
FDA recently discussed the increasing number of low positive samples, in which the number of virus in a sample is low, yet still exists. While there were 10-20% of such cases last year, the number constantly increases, reaching 30-40% this year. With 40% of COVID-19 test results turning up as low positives, the sensitivity of testing becomes increasingly important.
CDC had previously conducted a comparison test between antigen tests and PCR sensitivity. Result shows that the sensitivity of antigen tests was 64.2% and 35.8% on symptomatic and asymptomatic patients, respectively. Meanwhile, the sensitivity of rRT-PCR were 92.6% on symptomatic cases and 78.6% on asymptomatic cases, showing that PCR is much more reliable. CDC further warned: "inability to isolate virus from a clinical sample should not be interpreted to mean that a person is not infectious and incapable of transmission".
The biggest advantages of antigen tests are convenience and time-saving. People could conduct the test at home and the result would come in as fast as 15 minutes. However, FDA stated that serial testing should be conducted when using most antigen tests. User should perform two antigen tests over three days, with 24 to 48 hours between the tests. With that being a requirement, is 'time-saving' still an advantage of antigen tests? In contrast, the result of PCR, which is much more reliable, could be obtained as soon as a few hours after the test.
Depending on the process and number of samples, the process of obtaining and reporting PCR analysis could be done in a few hours. Generally, COVID-19 molecular test consists of sample collection, virus isolation and amplification (PCR). Swabs and saliva are the most commonly used samples in COVID-19 detection, but others such as blood, BAL, aspirates or other body fluids could also be tested for COVID-19. After collecting these samples, virus isolation proceeds.
The speed and efficiency of virus isolation process affects its following steps. When doing manual isolation / extraction, a trained operator might need hours to isolate COVID-19 nucleic acid from 100 samples before finally sending the samples for PCR. When using an automated extractor such as TANBead Maelstrom 9610, paired with the OptiPure Viral Reagent Kit (665), 1-96 samples could be extracted in 30-40 minutes. However, this process could be sped up even more with Virapid Viral Kit (685), which could finish the extraction process in 14-17 minutes. Therefore, patients would be able to get their PCR reports much quicker than conducting serial testing with rapid/antigen tests.
Aside from the sensitivity and time aspects, FDA also discussed the continuous mutations of COVID-19 strains. The Omicron variant significantly has more mutations than its predecessors, continuously changing its S-gene which encodes the virus' spiked protein. Both antigen and PCR tests are designed for multiple COVID-19 variants, thus the sensitivity towards specific target might be reduced. However, PCR test could be immediately followed up with sequencing in cases of gene dropout. Therefore, false negatives are less likely with PCR.
As of July 8th 2022, FDA had authorized 438 tests and sample collection devices under emergency use authorizations (EUAs). These include 303 molecular tests and sample collection devices, 85 antibody and other immune response tests, 49 antigen tests, and 1 diagnostic breath test.