COVID-19 Testing

SARS-CoV-2 causes COVID-19 and has led to a pandemic and a national public health emergency in the United States. The environment surrounding COVID-19 testing is continually evolving, and clinicians are encouraged to consult the CDC for the most current testing recommendations. 

Identification of patients infected with SARS-CoV-2 can help to isolate cases and prevent further person-to-person transmission, thus slowing the spread of infection, limiting the number of cases, and mitigating the impact on healthcare resources.  

Molecular diagnostic testing by nucleic acid amplification (NAA) is recommended for SARS-CoV-2 diagnosis.  Testing decisions should be based on local epidemiology, clinical signs and symptoms, and the course of illness. 

Saliva has recently been validated as an additional specimen type for the SARS-CoV-2 (COVID-19) by NAA test after having been determined in a study performed by ARUP and the University of Utah  to be an effective alternative to a nasopharyngeal swab specimen. Both saliva and nasopharyngeal swab specimens were found to be superior to anterior nasal swab specimens. Refer to the specimen collection instructions in the ARUP Lab Test Directory for additional information.

False-positive results are possible in low-prevalence settings, even when an antibody test has >98.0% specificity. The CDC Interim Guidelines for COVID-19 Antibody Testing  suggest using serologic assays with very high sensitivity and specificity due to their likelihood to exhibit high expected predictive values.

Disease Overview

Incidence

In early 2020, COVID-19 spread rapidly across the globe. Updated case counts can be found in the World Health Organization’s Coronavirus Disease (COVID-2019) Weekly Epidemiological Update  and on the CDC’s United States COVID-19 Cases and Deaths by State web page. 

Symptoms

Clinical presentation ranges from asymptomatic infection to mild symptoms to more severe illness. Symptoms may not appear until 14 days after exposure, but the median time from exposure to symptom onset is 4-5 days.  

Symptoms of possible COVID-19 include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, myalgia, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.  

Emergency warning signs of COVID-19 include the following :

• Difficulty breathing
• Persistent pain or pressure in the chest
• New confusion
• Inability to wake or remain awake
• Bluish lips or face

Transmission

• The virus spreads through respiratory droplets produced when an infected person coughs, sneezes, or talks. 
• These respiratory droplets can pass into the mouths or noses of people nearby or may be inhaled. 

Molecular Diagnostic Test

SARS-CoV-2 (COVID-19) by NAA

This NAA assay is performed on the Hologic platform and is used to detect  SARS-CoV-2.

Results

Results are reported as SARS-CoV-2 detected, not detected, or invalid.

Specificity

This assay detects the 2019 novel coronavirus strain (SARS-CoV-2). The assay was shown by the manufacturer via direct testing or in silico analysis to not cross-react with a large number of other bacteria and viruses. Hologic is monitoring SARS-CoV-2 variants, including the Alpha and Delta variants, to understand what impact, if any, these variants have on the specificity of this assay.

ARUP’s SARS-CoV-2 assay gene targets are Orf1ab/O-methyltransferase at two different sites, and the assay can detect the Alpha, Beta, Delta, and Gamma variants of SARS-CoV-2.

Limitations

• A negative result does not preclude SARS-CoV-2 and should not be used as the sole basis for patient management decisions.
• A negative result must be combined with other clinical observations, patient history, and epidemiologic information.
• A positive result indicates the detection of nucleic acid from the relevant virus.
  • Nucleic acid may persist even after the virus is no longer viable.
• Positive results do not rule out bacterial infection or coinfection with other viruses.
• Reliable results are dependent on adequate specimen collection, transport, storage, and processing.
• Theoretically, assay sensitivity might be decreased in viral variants with mutations in several regions targeted by the assays. The assay manufacturers are continuously monitoring available variant sequences to ensure their assays are detecting emerging variants.

COVID-19 IgG (Serology)

COVID-19 IgG, Qualitative by CIA (Target: Nucleocapsid Protein)

This CIA assay, developed by Abbott and performed on the Architect platform, detects IgG antibodies specific to the nucleocapsid protein of SARS-CoV-2 that form as a result of natural SARS-CoV-2 infection. This test is reported as negative or positive.

This 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. 

COVID-19 IgG, Semi-Quantitative by CIA (Target: Spike Protein)

This semiquantitative CIA assay, developed by Siemens and performed on the ADVIA Centaur XPT platform, detects IgG antibodies specific to the S1 domain of the spike protein of SARS-CoV-2 that develop in response to natural SARS-CoV-2 infection or to COVID-19 vaccination. This test is reported as negative or positive and includes an index value. The American Association for Clinical Chemistry (AACC) does not recommend the use of serology for assessing COVID-19 vaccine response. 

This and other serology tests for COVID-19 offered by ARUP have been evaluated by both the manufacturer and the FDA in partnership with the NIH, the CDC, and BARDA. Please visit the FDA web page, EUA Authorized Serology Test Performance, for more information. 

Serology Limitations

• Antibody test results should not be used as the sole criterion to confirm or rule out SARS-CoV-2 infection or to assess infection status.
• There are no current recommendations for assessing COVID-19 vaccine response. 
• Negative results do not exclude infection with SARS-CoV-2, especially in individuals with known exposure to the virus.
  • Follow-up molecular diagnostic testing should be considered in those with recent exposure to COVID-19.
  • Immunocompromised patients infected with COVID-19 may have a delayed antibody response or antibody levels too low to result in a positive test.
• Positive results suggest exposure to SARS-CoV-2 but may not indicate immunity.
• False-positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.
• COVID-19 serology tests are not for use in screening donated blood.