The evolution of the SARS-CoV-2 virus, which causes COVID-19, has led to the emergence of numerous variants, including various Omicron subvariants. This viral change raises questions about whether diagnostic tests can still reliably detect the newest strains. Most tests remain effective, but their success is tied directly to the specific method they use to identify the virus. Understanding the underlying science of these tests is crucial for interpreting results as the virus continues to evolve.
Understanding How COVID Tests Target the Virus
The two main types of tests used for current infection are Rapid Antigen Tests and Polymerase Chain Reaction (PCR) tests, which target different viral components. Rapid antigen tests detect specific proteins on the surface or inside the virus. Most commercially available antigen tests focus on identifying the Nucleocapsid (N) protein, an internal structural component of the virus.
PCR tests look for the virus’s genetic material, or RNA, using a process called Nucleic Acid Amplification. These laboratory-based tests seek out specific sequences of the viral genome, such as the genes that code for the N protein, the Spike (S) protein, or other non-structural proteins like ORF1ab. Because PCR tests amplify tiny amounts of RNA, they are considered the gold standard for sensitivity, though they take longer to process than antigen tests.
How Viral Mutations Impact Test Accuracy
Viruses accumulate small changes, or mutations, in their genetic code as they replicate. If a mutation occurs in the specific region targeted by a test, the test’s ability to detect the virus may be reduced.
For an antigen test, a mutation in the N protein could alter its shape, making it harder for the test’s antibodies to bind and potentially causing a false negative result. In a PCR test, a mutation in a targeted genetic segment could prevent the test’s chemical primers from attaching to the viral RNA. This target-site mutation is the primary concern for test reliability as new variants emerge, but continuous monitoring helps ensure tests remain accurate.
Reliability of Rapid Antigen Tests Against Current Variants
Most rapid antigen tests have demonstrated continued effectiveness against the latest circulating variants. This is largely because the Nucleocapsid (N) protein, the target for most rapid tests, has remained relatively stable compared to the highly-mutated Spike (S) protein. Although the N protein is not immune to change, the specific regions targeted by the antibodies in the test kits have proven resilient.
The primary limitation of rapid antigen tests remains their sensitivity, or their ability to detect low levels of the virus. Studies show that while they work against new variants, sensitivity may be lower early in an infection, especially when the viral load is low. If you have symptoms but test negative on an antigen test, it is recommended to repeat the test after 48 hours to account for a rising viral load.
Reliability of PCR Tests Against Current Variants
PCR tests maintain a high degree of reliability against current variants due to their multi-target design. These laboratory tests look for two or more distinct genetic segments on the SARS-CoV-2 genome. If a mutation causes one target, such as the S-gene, to fail to amplify, the test can still yield a positive result by detecting the other targets, like the N or ORF1ab genes.
The non-detection of the S-gene, known as S-gene target failure (SGTF), is used by public health officials as an early marker to track the spread of specific variants. SGTF is a monitoring tool for surveillance, not an indication of a failed test result. Because multiple genetic targets are included in the test design, the overall sensitivity of the PCR test remains unaffected.
Interpreting Your Test Results
A positive result on any test, whether rapid antigen or PCR, indicates a current infection with the virus. Anyone with a positive result should follow current public health guidelines for isolation to prevent transmission. If you have symptoms but receive a negative result on a rapid antigen test, do not assume you are uninfected, as the test may have been performed too early.
In this scenario, it is recommended to take a second antigen test 48 hours later, or seek a molecular PCR test. Even with a negative result, taking precautions like wearing a high-quality mask when around others is advisable until symptoms resolve. A single negative test only confirms that the viral load was below the test’s detection threshold at that specific moment.