COVID-19 - SARS-CoV-2

Last Literature Review: July 2022 Last Update:

Medical Experts

Contributor

Barker

Adam Barker, PhD
Assistant Professor of Pathology (Clinical), University of Utah
Chief Operations Officer, ARUP Laboratories
Medical Director, Next Generation Sequencing (NGS) Infectious Disease, R&D Special Operations, Reagent Laboratory, Technology Transfer, Transportation
Contributor
Contributor

Slev

Patricia R. Slev, PhD, D(ABCC)
Professor of Pathology (Clinical), University of Utah
Section Chief, Immunology; Medical Director, Immunology Core Laboratory, ARUP Laboratories

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is one of a large family of respiratory viruses and is spread from person to person through the respiratory route of transmission. Whereas common coronaviruses usually produce mild illness, in certain populations (eg, individuals with immune compromise), infection can lead to more severe illness. The gold standard for COVID-19 diagnosis is molecular testing (ie, nucleic acid amplification testing [NAAT]).  Antigen testing may also be considered during the acute phase of infection.  Serology (antibody testing) is not recommended for diagnosis of acute COVID-19 but may be used to evaluate for previous SARS-CoV-2 infection or suspected multisystem inflammatory syndrome (MIS). 

Quick Answers for Clinicians

What is the role of serologic testing (ie, antibody testing) in COVID-19?

Although serology is generally not recommended to diagnose acute COVID-19, it may be appropriate in other contexts to identify a SARS-CoV-2 infection. The Infectious Diseases Society of America (IDSA) recommends immunoglobulin G (IgG) antibody testing in combination with nucleic acid amplification testing (NAAT) to assess for present or recent COVID-19 in individuals with associated complications (eg, children with suspected multisystem inflammatory syndrome [MIS]). In addition, IgG, combined IgG/IgM, or total antibody testing may be used 3-5 weeks after symptom onset for general confirmation of recent COVID-19. Antibodies against the spike protein have a low positive predictive value due the prevalence of COVID-19 vaccination, so assays targeting the nucleocapsid protein are suggested. 

Indications for Testing

Laboratory testing is appropriate in individuals with known or suspected exposure to SARS-CoV-2.  Testing may also be considered to provide evidence of previous SARS-CoV-2 infection. 

Laboratory Testing

Molecular Diagnostic Testing

Molecular assays (eg, by NAAT) are used to detect SARS-CoV-2 in respiratory specimens and are considered the gold standard for COVID-19 diagnosis. In asymptomatic individuals, testing can be performed at least 5 days after exposure. Retesting is not routinely recommended but may be considered if the timing of testing or poor specimen collection is suspected to have caused a false-negative result. Repeat testing may also be considered in the presence of new or worsening symptoms when no other cause can be identified. 

Antigen Testing

Antigen testing, performed on nasal or throat swab specimens, can be used for rapid detection of a SARS-CoV-2 infection in a point-of-care setting. Ideally, testing should be performed within 5 days of symptomatic illness. When used under optimal conditions, the negative predictive value of antigen testing is high; however, in the event of a negative antigen result, NAAT may be considered if suspicion for COVID-19 remains. If NAAT is not available, a second antigen test can be performed no later than 5 days after symptom onset. Antigen testing has reduced sensitivity when used in the absence of symptoms or late in the course of illness. 

Serologic Testing

Serologic testing, also known as antibody testing, is used to detect antibodies against SARS-CoV-2 in serum or plasma. Due to the low sensitivity (ie, high likelihood of false-negative results) of this testing when performed within the first 2 weeks of symptomatic illness, the Infectious Diseases Society of America (IDSA) recommends against serologic testing to diagnose acute COVID-19. However, immunoglobulin G (IgG), combined IgG/IgM, or total antibody testing may be used 3-5 weeks after symptom onset for general confirmation of recent COVID-19. Assays that target the nucleocapsid protein are recommended due to the prevalence of vaccination using antibodies against the spike protein. 

In addition to confirming previous infection, antibody testing may be used in conjunction with NAAT to assess for MIS, a serious complication of COVID-19 ; refer to the CDC’s case definitions for MIS in children and adults  for more information.

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Molecular Diagnostic Testing
Serologic Testing