Testing for SARS-CoV-2 using a molecular method such as NAA (nucleic acid amplification) is recommended for symptomatic patients. Since symptoms are similar to other respiratory infections, a clinical diagnosis alone is not sufficient to make a COVID-19 diagnosis.

Both antigen and molecular tests perform best when patients are symptomatic. Generally, COVID-19 antigen tests are less sensitive than molecular methods. NAA (nucleic acid amplification) testing is the recommended diagnostic test for the diagnosis of a COVID-19 infection.¹

ARUP currently offers a COVID-19 nucleic acid amplification (NAA) assay that can be performed using either of two methodologies, reverse transcription polymerase chain reaction (RT-PCR) or transcription-mediated amplification (TMA). The RT-PCR tests are manufactured by Hologic and Roche, and the TMA test is manufactured by Hologic. The Hologic tests are performed on the Panther system, and the Roche test is run on the Cobas 6800 system. The Hologic and Roche assays do not use the S gene as an amplification target, and thus their performance is unaffected by S gene mutations.

Genetic sequencing is required to fully characterize and identify a particular SARS-CoV-2 strain. ARUP’s Hologic and Roche SARS-CoV-2 assays use several gene targets. These multiple targets allow the assays to detect genetic variants by adding redundancy.

The assays can detect the Alpha, Beta, Delta, Gamma, and Omicron variants of SARS-CoV-2. Currently, there have been no detected mutations or viral variants that will not be detected by the assay offered by ARUP Laboratories. There is no difference in treatment based on the specific SARS-CoV-2 variant.

More information about COVID-19 variants can be found on the CDC’s website.² Additionally, you can refer to this U.S. Food and Drug Administration (FDA)³ resource for more information about SARS-CoV-2 variants and their possible impact on laboratory testing.

ARUP does not currently offer a SARS-CoV-2 sequencing test to clients. ARUP is required to send a percentage of positive specimens to the state health department for sequencing and variant identification for public health management.

Hologic and Roche, the manufacturers of the platforms used by ARUP to perform NAA testing, are continuously monitoring available sequences of SARS-CoV-2 strains to ensure that their assays are detecting emerging variants and to understand any implications of these mutations. Currently, there have been no detected mutations or viral variants that will not be detected by the assay offered by ARUP Laboratories.

Generally, immunoglobulin M (IgM) antibodies are the first antibodies the body produces in response to an infection, usually appear within a week of infection, and disappear within a month or two. IgG antibodies typically develop after IgM and may remain detectable for months or years, although the time period that IgG antibodies persist in those who have had COVID-19 is still being determined. However, in COVID-19, IgM and IgG develop almost simultaneously, generally 7–14 days after symptom onset, in response to SARS-CoV-2 infection. IgM antibodies persist for only a few weeks, whereas IgG levels are more durable and can sometimes be detected for months after natural infection. IgA and standalone IgM tests are not recommended for SARS-CoV-2 serology testing.⁴ Total antibody and IgG assays should be used instead. Several studies have reported detectable IgG response several months after infection or vaccination using IgG assays.

COVID-19 vaccination produces antibodies against the SARS-CoV-2 spike protein. These antibodies can be detected by several serology tests, including ARUP’s COVID-19 IgG (Spike), Semi-Quantitative by CIA (3003648) assay. However, it has not yet been established that the presence of SARS-CoV-2 IgG antibodies implies protective immunity. Data are insufficient to define a threshold for protective immunity, so we cannot properly interpret whether or not a patient is protected from symptomatic disease or reinfection. The American Association for Clinical Chemistry (AACC) does not currently recommend the use of serology to assess vaccination response.⁴

The table below details the potential results of molecular diagnostic or serology assays and their interpretations.

No test is perfect. Occasionally, tests can yield a false-positive or false-negative result. Molecular diagnostic testing is highly specific, meaning that the test is designed to detect the unique genetic sequence of SARS-CoV-2. If a test result is positive, you can be confident that the virus was detected.

False-negative results may occur depending on the specimen tested and the timing of the sample collection. If testing is performed early in the infectious process, before symptoms occur, test results may be falsely negative. A false-negative result is also possible if a person is tested late in the course of the infection, when symptoms have waned.

No test is perfect. Occasionally, antibody tests can return false-positive or false-negative results. If a specimen is collected too early, antibody tests can yield false-negative results. False-positive results are possible in a small percentage of individuals. These may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

These and other serology tests for COVID-19 offered by ARUP have been evaluated by both the manufacturer and the U.S. Food and Drug Administration (FDA) in partnership with the National Institutes of Health (NIH), the CDC, and the Biomedical Advanced Research and Development Authority (BARDA). Please visit the FDA web page, EUA Authorized Serology Test Performance, for more information.