Novel Coronavirus Disease 2019 (COVID-19) - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

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 the recently discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease 2019 (COVID-19), can lead to more severe illness.

As of spring 2020, SARS-CoV-2 is widespread in the United States and many other countries. Spread of infection has been person-to-person through the respiratory route of transmission, similar to other respiratory viruses. Identification of patients with SARS-CoV-2 can help to isolate cases and prevent further person-to-person transmission, thus limiting the number of cases, slowing the spread of infection, and mitigating the impact on healthcare resources. 

Molecular testing is recommended for COVID-19 diagnosis.  Testing decisions should be based on local epidemiology, clinical signs and symptoms, and the course of illness. Serology testing is recommended for evaluating exposure to SARS-CoV-2. Serology testing is not recommended for diagnosis of acute illness.

The environment surrounding COVID-19 testing is evolving rapidly. Clinicians are advised to consult the CDC for the most current testing priorities and recommendations  and ARUP’s Response to Coronavirus Disease 2019 (COVID-19) page for our most up-to-date testing information.

Quick Answers for Clinicians

What are the clinical features of COVID-19 in adults?

Clinical presentation ranges from asymptomatic infection to mild, acute upper respiratory symptoms to more severe flulike illness and pneumonia. Frequently reported symptoms of patients admitted to the hospital include fever, cough, and shortness of breath. 

How does COVID-19 affect children?

Based on available evidence, children do not appear to be at higher risk for COVID-19 than adults. Limited information is available about the spectrum of clinical illness related to COVID-19 in children, although they do appear to present with more mild signs and symptoms than adults.  Although severe disease is uncommon, early case studies and reports suggest that infants may be at a higher risk for severe illness from COVID-19 when compared with older children. 

The CDC is investigating reports of multisystem inflammatory syndrome in children (MIS-C), a serious condition marked by inflammation that may be related to resolved COVID-19 infection. At this time, there is limited information available about risk factors, pathogenesis, and clinical course. The CDC has issued a health advisory instructing clinicians to watch for signs and symptoms, which may include a persistent fever, elevated inflammatory markers, and multiorgan (eg, cardiac, gastrointestinal, renal) involvement. 

Who should receive diagnostic testing for COVID-19?

The CDC prioritizes certain groups (eg, symptomatic individuals who are hospitalized, working in healthcare facilities, or living in any congregate living areas) for testing.  The Infectious Diseases Society of America (IDSA) recommends that all symptomatic individuals be tested for COVID-19, and, in certain scenarios, asymptomatic individuals should also be tested.  Refer to the Indications for Testing for specific recommendations. The environment surrounding COVID-19 testing is evolving rapidly. For the most up-to-date guidance, please visit the CDC’s Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19) page.  

Local and regional health authorities may provide additional guidance for prioritizing patients for COVID-19 testing. Clinicians are also encouraged to consider testing for other causes of respiratory illness, including influenza.

What are the risk factors for severe COVID-19 disease?

Data are still limited, but older patients and those with chronic medical conditions appear to be at higher risk for severe illness if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 

Do existing respiratory virus panels detect SARS-CoV-2?

Yes, some multipathogen molecular assays can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).  Clinicians are advised to confirm which respiratory viruses are detected by an assay before ordering.

Which laboratory tests are available for COVID-19 testing?

Nucleic acid amplification tests (NAATs) are recommended to diagnose COVID-19.  Rapid point-of-care tests based on isothermal amplification are also available. An Infectious Diseases Society of America (IDSA) panel determined that there is currently not enough evidence to recommend for or against rapid RNA testing in symptomatic individuals suspected of having COVID-19. 

Serology testing is used to evaluate exposure to the COVID-19 virus. Two types of serology tests are available—laboratory-based immunoassays and rapid lateral flow immunoassays that can be used near the point of care. Some tests detect total antibodies, whereas others detect specific isotypes (immunoglobulin G [IgG], IgM, IgA).

Which specimens are acceptable for COVID-19 testing? Which collection media is preferred?

Nasopharyngeal (NP) specimens are preferred for swab-based COVID-19 diagnostic testing. If NP specimens are not available, an oropharyngeal (OP), midturbinate, or anterior nares specimen is acceptable.   Detection rates in specimen types vary from patient to patient and may change over the course of the illness. For example, because of potentially discordant shedding of virus in the upper versus the lower respiratory tract, patients with pneumonia may have negative nasal or OP samples but positive lower airway samples.  

Swab specimens should be collected with NP ultrafine or equivalent swabs. Dacron, polyester-tipped, or any other flocked swabs are acceptable alternatives. Calcium alginate swabs or swabs with wooden shafts are NOT acceptable due to test interference. Viral transport media and universal transport media (VTM/UTM) are the preferred collection systems for swabs. Media types that are equivalent to VTM/UTM are also acceptable. For alternative transport media, refer to the FDA’s guidance on specimen collection for SARS-CoV-2 molecular diagnostic testing. 

Some laboratories may accept alternative specimen types; clinicians are advised to check with their performing laboratory for specific specimen requirements. There are limited data on how alternative specimen types affect test sensitivity, but evidence thus far suggests that specimens such as nasal swabs may be less sensitive than NP swabs. 

Serum or plasma specimens are the appropriate specimen types for antibody testing.

Indications for Testing

Diagnostic Testing

In the U.S., the CDC and the Infectious Diseases Society of America (IDSA) have suggested groups for prioritized COVID-19 testing. Prioritization of patients is important because a rapid increase in test demand could exceed the capacity of laboratories as well as the ability of manufacturers to supply test kits and reagents. Local and regional health authorities may provide additional guidance.

The CDC recommends the following categories of prioritization for the molecular diagnostic testing of patients for suspected COVID-19.

 
CDC's Priorities for Testing Patients with Suspected COVID-19 Infection

High priority

  • Hospitalized patients with symptoms
  • Healthcare facility workers, workers in congregate living settings, and first responders with symptoms
  • Residents in long-term care facilities or other congregate living settings, including prisons and shelters, with symptoms

Priority

  • Persons with symptoms of a possible infection with COVID-19, including fever, cough, shortness of breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or sore throat
  • Persons without symptoms who are prioritized by health departments or clinicians, for any reason, including but not limited to public health monitoring, sentinel surveillance, or screening of other asymptomatic individuals according to state and local plans
Source: CDC, Evaluation and Testing 

The IDSA also recommends that certain asymptomatic individuals undergo testing.

IDSA Recommendations for Testing Patients with Suspected COVID-19 Infection

Test symptomatic individuals who:

  • Have symptoms of a possible infection with COVID-19, even when clinical suspicion is low

Test asymptomatic individuals who:

  • Have a known or suspected exposure to COVID-19
  • Have had no known exposure to COVID-19 but are being hospitalized in areas with a high prevalence of COVID-19 in the community (eg, hotspots)
  • Are immunocompromised and are being admitted to the hospital
  • Are undergoing an immunosuppressive procedure, regardless of a known exposure to COVID-19
  • Are undergoing major time-sensitive surgeries, but have no known exposure to COVID-19
  • Are undergoing a time-sensitive aerosol-generating procedure (eg, bronchoscopy) when PPE is limited and testing is available, but have no known exposure to COVID-19
Source: IDSA 

Testing for Exposure

Exposure to COVID-19 can be assessed by serology testing. This testing is not recommended for diagnosis and should not be used for patients in the acute phase of infection.

Laboratory Testing

Diagnosis

Molecular Diagnostic Testing

Molecular diagnostic assays, such as nucleic acid amplification tests (NAATs), are used to detect SARS-CoV-2 in respiratory specimens of patients suspected of having 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.  

Overall test sensitivity may be reduced if optimal sample collection is not followed. Early data suggest that some specimens, including nasal swabs, may lead to reduced test sensitivity as compared with NP swabs. 

In some situations, it may be advisable to obtain a lower respiratory tract specimen for diagnostic testing because these specimens are thought to carry a higher viral load than upper respiratory tract specimens.  Due to the high specificity of NAAT, a positive result based on an upper respiratory tract specimen is generally adequate to establish a COVID-19 diagnosis. For this reason, the IDSA panel suggests initially obtaining an upper respiratory tract sample rather than a lower respiratory sample when testing hospitalized patients with suspected COVID-19 lower respiratory tract infection. However, if the initial upper respiratory sample result is negative and the suspicion for disease remains high, the panel suggests collecting a lower respiratory tract sample rather than collecting another upper respiratory sample. 

In intubated and mechanically ventilated patients for whom COVID-19 status is unknown, the National Institutes of Health (NIH) recommends carefully collecting a lower respiratory tract specimen for diagnostic testing.

Testing for Exposure

Serology Testing

Serology testing, also known as antibody testing, is used to detect antibodies against SARS-CoV-2 in serum or plasma. Early studies suggest the majority of patients with COVID-19 seroconvert around two weeks after symptom onset; because of this natural delay, serology testing is not recommended for COVID-19 diagnosis.    Furthermore, there are not enough data available to determine if protective immunity is consistently achieved in all patients after infection and if that immunity wanes and/or disappears over time.   

Although antibody testing is not recommended to diagnose infection or to infer an individual’s immunity to the virus, it may aid in determining the rate of exposure in a given population. Antibody testing can also help identify individuals who have been exposed to SARS-CoV-2 in order to qualify potential convalescent plasma donors. COVID-19 convalescent plasma is currently being researched as a possible treatment for individuals who are critically ill with COVID-19 and as a prophylactic means of protecting individuals at high risk of exposure. 

Serology testing should be interpreted in the context of expected predictive values. False-positive results are possible in low-prevalence settings, even when an antibody test has >98% specificity. To reduce the likelihood of a false-positive result, the CDC recommends maximizing overall specificity  by using a combination of one or more of the following strategies :

  • Testing individuals with a high pretest probability of having antibodies (eg, individuals who have a history of illness consistent with COVID-19 infection)
  • Choosing a test with very high specificity
  • Using an orthogonal testing algorithm so that individuals who are positive by one antibody assay are retested with a second antibody test

ARUP offers two tests for immunoglobulin G (IgG) antibodies that target different SARS-CoV-2 proteins. One test detects IgG against the nucleocapsid protein, and the other test detects IgG against the S1 domain of the spike protein. These two tests can be used in the orthogonal testing algorithm, as described above, to minimize the number of false-positive results in low-prevalence settings.

Other Testing

Cytokine Testing

Early data suggest that in some patients, COVID-19 may trigger cytokine storm syndrome, a phenomena marked by hyperinduction of proinflammatory cytokine production.

Cytokine testing is used primarily for research and to support attempts to understand the pathogenesis of immune, infectious, allergic, or inflammatory disorders. There are currently no well-defined guidelines on how the results should be interpreted and/or used to guide treatment decisions in COVID-19.

Hemostasis Testing

Increased venous thromboembolism (VTE) and arterial thrombotic events (eg, myocardial infarction, stroke) have been described in patients with severe COVID-19.  However, the exact contributing factors to the observed increase in thrombotic risk are not yet fully understood.     The most likely mechanism behind most of the thrombotic risk and coagulation test abnormalities appears to be endothelial damage within the lungs, which triggers inflammatory and coagulation cascades. 

Disseminated intravascular coagulation (DIC) is another thrombotic mechanism that affects some patients, particularly those who are critically ill. Elevated D-dimer has been described in patients with COVID-19 infection who require intensive care unit (ICU) admission, but the elevation is not always to the very high level expected with DIC.    In one single-center study from Wuhan, China, ~70% of patients who died of COVID-19 met current diagnostic criteria for DIC as set forth by the International Society of Thrombosis and Haemostasis (ISTH).  Prothrombin time (PT) may be mildly prolonged at admission in patients with COVID-19.   Thrombocytopenia has been reported in some but not all patients with COVID-19.  

Hyperfibrinogenemia has been reported in individuals with COVID-19, which may lead to increased fibrin formation and polymerization, increased thrombotic risk, and elevated D-dimer. 

Lupus anticoagulant and antiphospholipid antibodies have been reported in patients with COVID-19, but the significance of this finding is uncertain, given that transient antiphospholipid antibodies (present for <12 weeks) are described with other acute infections and do not necessarily represent a thrombotic risk factor.  

Bleeding complications have not been widely reported in those with COVID-19.  Platelet counts are variable in patients with COVID-19. One meta-analysis indicated that thrombocytopenia was more prominent in patients with more severe COVID-19.  Low platelet counts have not been observed in all case series of patients with COVID-19. 

The therapeutic implications and prognostic relevance of the abnormal hemostasis laboratory findings in COVID-19 are as yet unclear, and additional studies are needed. Prophylactic or even therapeutic anticoagulation has been used in hospitalized patients with COVID-19, and recommendations around this are currently evolving. 

Mental Health Testing

Mental health issues that have been exacerbated by the pandemic include stress, depression, and anxiety. Drugs used to treat mental health conditions such as major depressive disorder are some of the most widely prescribed drugs in the U.S. However, these medications are highly variable in terms of patient response and are associated with undesirable side effects. Pharmacogenetic testing and/or therapeutic drug monitoring may assist in the mental health care and management of patients with COVID-19.

Pharmacogenetic testing assesses genetic variations associated with drug response or drug disposition that may predispose a patient to be at risk for drug-related toxicity, nonstandard dose requirements, or lack of therapeutic benefit. Refer to the ARUP Consult Pharmacogenetics topic for examples of antidepressant testing.

Therapeutic drug monitoring is the clinical practice of measuring specific drugs or their metabolites at designated intervals to maintain a therapeutic concentration in a patient’s bloodstream and optimize individual dosage regimens. Refer to the ARUP Consult Therapeutic Drug Monitoring topic for examples of antidepressant and antipsychotic tests.

ARUP Lab Tests

Molecular Diagnostic Testing

Detects the 2019 novel coronavirus (SARS-CoV-2)

ARUP is accepting new COVID-19 molecular test orders from clients with prior authorization; for more information about the authorization process, please contact Client Services at (800) 522-2787

Serology Testing for Exposure

Detects IgG antibodies against the nucleocapsid protein of SARS-CoV-2 to evaluate exposure

To reduce the likelihood of a false-positive result, the CDC suggests using an orthogonal testing algorithm so that individuals positive by one antibody test are retested with a second antibody test (refer to COVID-19 IgG by ELISA)

Results are reported as “negative” or “positive”

Not recommended for COVID-19 diagnosis

This test is available under the FDA’s Emergency Use Authorization (EUA)

Detects IgG antibodies against the spike protein (S1) of SARS-CoV-2 to evaluate exposure

To reduce the likelihood of a false-positive result, the CDC suggests using an orthogonal testing algorithm so that individuals positive by one antibody test are retested with a second antibody test (refer to COVID-19 IgG, Qualitative by CIA)

Results are reported as “negative,” “positive,” or “indeterminate” and will include an index value

Not recommended for COVID-19 diagnosis

This test is available under the FDA’s Emergency Use Authorization (EUA)

Cytokine Testing

Primarily used for research and to support attempts to understand the pathogenesis of immune, infectious, allergic, or inflammatory disorders

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor
Medical Reviewer
Contributor

McMillin

Gwendolyn A. McMillin, PhD
Professor of Clinical Pathology, University of Utah
Scientific Director, Mass Spectrometry Platform; Medical Director, Clinical Toxicology and Pharmacogenomics, ARUP Laboratories
Contributor

Moser

Karen A. Moser, MD
Assistant Professor of Clinical Pathology, University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories
Contributor
Contributor

Rychert

Jenna Rychert, PhD, ABMM
Adjunct Assistant Professor of Clinical Pathology, University of Utah
Medical Director, Microbial Immunology, ARUP Laboratories
Contributor

Slev

Patricia R. Slev, PhD
Associate Professor of Clinical Pathology, University of Utah
Section Chief, Immunology; Medical Director, Immunology Core Laboratory, ARUP Laboratories
Contributor

Smock

Kristi J. Smock, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

References

Additional Resources