Coronaviruses are a large family of respiratory viruses. Common coronaviruses usually cause mild illness. Rarer coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, which causes COVID-19, can lead to more severe illness. SARS-CoV-2 infection is spread person-to-person through the respiratory route of transmission. Viral detection is recommended for COVID-19 diagnosis. The gold standard is molecular (nucleic acid amplification) testing.  Serology (antibody) testing is recommended for evaluating exposure to SARS-CoV-2; it is not recommended for the diagnosis of acute illness.

Quick Answers for Clinicians

What is serology testing used for in COVID-19?

Serology (also known as antibody) testing is used to evaluate exposure to the virus that causes COVID-19. When testing for COVID-19, immunoglobulin M (IgM) and IgA antibodies are generally not considered clinically useful. Although antibody testing should not be used as an initial diagnostic test, there are circumstances in which this testing might be useful for diagnosing later-stage disease. For example, antibody testing can be used to evaluate individuals presenting with COVID-19-like disease but late in the course of the illness (when the sensitivity of molecular diagnostic testing is decreased) and individuals with late complications of suspected COVID-19 disease (eg, multisystem inflammatory syndrome in children [MIS-C]). 

Which specimens are acceptable for COVID-19 testing?

Nasopharyngeal (NP) specimens are the gold standard for COVID-19 viral detection. Some laboratories may accept alternative specimen types such as saliva, oropharyngeal (OP) swab, mid turbinate swab, or anterior nares swab specimens.  Clinicians are advised to check with their performing laboratories for specific specimen requirements. For more information about the specimen collection requirements at ARUP Laboratories, see the SARS-CoV-2 (COVID-19) by NAA: Specimen Collection and Shipping Instructions.

Will nucleic acid amplification tests detect variants of SARS-CoV-2 with mutations in the spike protein (S gene)?

Variants, including the Delta and Omicron variants, may impact the results of molecular tests that utilize genetic targets that include the site of mutation. However, most assays include multiple genetic targets, which allows for redundancy so that natural viral variation is less likely to impact test performance.

ARUP currently performs nucleic acid amplification testing (NAAT) for SARS-CoV-2 on two different platforms, Hologic and Roche. The COVID-19 NAA standalone assay is performed using either of two methodologies, reverse transcription polymerase chain reaction (RT-PCR) or transcription-mediated amplification (TMA). These tests do not use the S gene as an amplification target, and their performance is unaffected by S gene mutations.

Can laboratory testing identify novel variants of SARS-CoV-2?

Most diagnostic assays utilize techniques such as polymerase chain reaction (PCR) and transcription-mediated amplification (TMA) and do not identify specific strains of a virus. For a particular strain to be characterized, the virus must undergo genetic sequencing. Because of this, routine diagnostic testing does not distinguish between wild-type SARS-CoV-2 and its variants, and further analysis using genetic sequencing is required.

ARUP does not currently offer a SARS-CoV-2 sequencing test to clients.

Indications for Testing

The CDC and the Infectious Diseases Society of America (IDSA) offer recommendations for SARS-CoV-2 laboratory testing. For detailed information about these recommendations, see the ­­­­­­­­­­­­­CDC’s Overview of Testing for SARS-CoV-2  and the IDSA Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. 

Laboratory Testing

Molecular Diagnostic Testing

Molecular diagnostic assays (eg, nucleic acid amplification testing [NAAT]) are used to detect SARS-CoV-2 in respiratory specimens of patients with suspected COVID-19.   A negative result indicates that SARS-CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not exclude the possibility of COVID-19 and should not be used as the sole basis for treatment or patient management. The possibility of a false-negative result should be considered if the patient’s recent exposures or clinical presentation suggests that COVID-19 is likely. Retesting may be advisable in symptomatic individuals with an intermediate or high clinical suspicion of COVID-19, and should be considered based on clinical judgment in combination with the recommendation of public health authorities. 

Antigen Testing

Antigen testing, performed on nasal or throat swab specimens, can also be used to detect SARS-CoV-2 infection. Antigen testing is often performed at the point of care, allowing for quicker results.  Antigen testing is less sensitive than NAAT and is associated with an increased risk of false-negative results. Because antigen testing requires a higher viral load for detection of SARS-CoV-2, it is most useful early in the course of illness when viral load is higher.   Clinicians should consider the performance characteristics of antigen tests when interpreting results.

Serology Testing

Serology testing, also known as antibody testing, is used to detect antibodies against SARS-CoV-2 in serum or plasma. Studies suggest the majority of patients with COVID-19 seroconvert approximately 2 weeks after symptom onset; because of this natural delay, serology testing is not recommended for COVID-19 diagnosis.  Both immunoglobulin M (IgM) and IgG develop almost simultaneously, generally 7-14 days after symptom onset, in response to SARS-CoV-2 infection. IgM persists for only a few weeks, whereas IgG levels are more durable and can sometimes be detected for months after natural infection. It is recommended that serology testing be performed 2-4 weeks after symptom onset. IgG and total antibody assays are useful for evaluating patients who present later in the disease course. 

Vaccination results in the production of antibodies to specific viral protein targets. Current emergency use authorization (EUA)-approved COVID-19 vaccines target the spike protein of SARS-CoV-2. Therefore, serology assays that use the spike protein as a target will detect antibodies that develop in response to vaccination or to natural infection. Serology assays that target antibodies that bind to different proteins, such as the nucleocapsid protein, should only detect antibodies from natural infection. Test selection and interpretation should consider the vaccination status of the patient.

Other Testing

Hemostasis Testing

COVID-19 is associated with an increased risk of thrombosis, and venous thromboembolism (VTE) is more common than arterial thrombosis. Bleeding is not commonly reported. The increased thrombotic risk is caused by endothelial cell activation and injury, inflammation with acute phasing of procoagulant factors such as von Willebrand factor (VWF) and fibrinogen, and activation of the coagulation system.  Several hemostatic laboratory abnormalities can be seen in COVID-19, particularly in cases of more severe disease. For example, elevated D-dimer (several times the upper limit of normal), thrombocytopenia, prolonged prothrombin time (PT), and decreased fibrinogen have been associated with more severe disease and a poor prognosis.  The International Society on Thrombosis and Haemostasis (ISTH) score for sepsis-induced coagulopathy (SIC) can be applied to patients with COVID-19 to help identify patients with more severe disease and those who may benefit from anticoagulation treament.    Trending of laboratory values can be used to monitor the coagulopathy and disease severity. A 2021 American Society of Hematology (ASH) guideline on thromboprophylaxis in patients with COVID-19 recommends prophylactic intensity anticoagulation in patients with critical or acute COVID-19-related illness but without clinically suspected or confirmed VTE.  Although lupus anticoagulants have been identified in a subset of patients with COVID-19, the relationship between antiphospholipid antibodies and the COVID-19 coagulopathy requires further study. 

Vaccine-Induced Immune Thrombotic Thrombocytopenia

A rare syndrome of unusual thrombotic events with thrombocytopenia has been reported in a small number of patients following receipt of two SARS-CoV-2 vaccines (ChAdOx1 nCov-19 [AstraZeneca] and Ad26.COV2.S [Johnson and Johnson/Janssen], both of which use recombinant adenovirus vectors).  This syndrome, referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS), is associated with platelet-activating antibodies directed against platelet factor 4 (PF4), but is clinically distinct from heparin-induced thrombocytopenia (HIT). Estimates of incidence vary by vaccine and among reporting locations. The Advisory Committee on Immunization Practices (ACIP) reported an incidence of one case of VITT per 263,000 doses of Ad26.COV2.S administered in the United States.  In light of concerns regarding VITT, in May 2022, the U.S. Food and Drug Administration (FDA) updated the EUA for Ad26.COV2.S vaccine to permit its use only in a limited subset of patients older than 18 years. 

Patients with VITT presented 5-24 days postvaccination with thrombocytopenia and thromboses, which were located in unusual anatomic sites in some cases (eg, in cases of cerebral venous sinus thrombosis [CVST]). None of the patients had heparin exposure before development of thrombosis; however, anti-PF4 enzyme-linked immunosorbent assays (ELISAs) (typically used for diagnosis of HIT) were positive. Commercially available anti-PF4 ELISA assays have been described to detect the pathologic antibodies in these patients, although there is variation between assays.  Commercially available ELISAs use plates coated with heparin-PF4 or polyanion-PF4, and these may have different performance characteristics. Latex immunoassays and chemiluminescent immunoassays for anti-PF4 antibodies have poor sensitivity for VITT and may be negative in patients with VITT.   Functional platelet assays for HIT, such as the serotonin release assay (SRA), showed more variable performance, and although some patients had positive results, others may show indeterminate or even negative results; PF4 supplementation may improve assay sensitivity.   Samples for antibody testing in patients with suspected VITT should be collected before initiation of intravenous immunoglobulin (IVIG) therapy. Investigation into VITT, including identification of optimal laboratory testing, is ongoing; please refer to emerging guidelines updated on an ongoing basis, such as the ISTH Interim Guidance for the Diagnosis and Treatment on Vaccine-Induced Immune Thrombotic Thrombocytopenia. 

ARUP Laboratory Tests

Molecular Diagnostic Testing
Serology Testing for Exposure
VITT Testing


Medical Experts



Adam Barker, PhD
Assistant Professor of Pathology (Clinical), University of Utah
Chief Operations Officer, ARUP Laboratories
Medical Director, AFB/Mycology, Reagent Laboratory, R&D Special Operations


David R. Hillyard, MD
Adjunct Associate Professor of Pathology, University of Utah
Medical Director, Molecular Infectious Diseases, ARUP Laboratories


Karen A. Moser, MD
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories


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


Kristi J. Smock, MD
Professor of Pathology (Clinical), University of Utah
Chief Medical Director, ARUP Institute for Clinical and Experimental Pathology
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories