Novel Coronavirus Disease 2019 (COVID-19) Testing

  • Evaluate respiratory symptoms consistent with COVID-19 in nasopharyngeal and/or oropharyngeal specimens obtained during the acute phase of infection from individuals who meet COVID-19 clinical and/or epidemiologic criteria 
  • This test is specific to SARS-CoV-2 and does not detect additional coronaviruses
  • This test is available under the FDA’s Emergency Use Authorization (EUA)
  • Use for the qualitative detection of IgG antibodies against the nucleocapsid protein of SARS-CoV-2 in serum and plasma to evaluate exposure
  • Not recommended for COVID-19 diagnosis
  • The presence of IgG antibodies does not indicate protective immunity
  • Test is available under the FDA’s Emergency Use Authorization (EUA)
  • Use for the detection of IgG antibodies against the spike protein (S1) of SARS-CoV-2 in serum and plasma to evaluate exposure
  • Not recommended for COVID-19 diagnosis
  • The presence of IgG antibodies may not indicate protective immunity
  • Test is available under the FDA’s Emergency Use Authorization (EUA)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (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 priorities and 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.   Nucleic acid amplification (NAA) testing is currently the only recommended method for SARS-CoV-2 diagnosis. Testing decisions should be based on local epidemiology, clinical signs and symptoms, and the course of illness.

Serology testing to detect antibodies to SARS-CoV-2 is now available. Early studies suggest that most patients seroconvert around 2 weeks after symptom onset. Serology testing is not recommended for COVID-19 diagnosis.

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) situation reports  and on the CDC’s Cases in the U.S. web page. 

Symptoms

Clinical presentation ranges from asymptomatic infection to mild, acute upper respiratory symptoms to more severe flulike illness and pneumonia. Symptoms may appear 2-14 days after exposure.   Symptoms of possible COVID-19 include fever, cough, shortness of breath, chills, myalgia, new loss of taste or smell, vomiting or diarrhea, and sore throat. 

Emergency warning signs of COVID-19 include the following :  

  • Difficulty breathing or shortness of breath
  • Persistent pain or pressure in the chest
  • New confusion or inability to arouse
  • Bluish lips or face

Transmission

  • The virus spreads through respiratory droplets produced when an infected person coughs or sneezes. 
  • Individuals may acquire SARS-CoV-2 by touching surfaces or objects with these droplets and then touching their eyes, nose, or mouth. 

Test Interpretation

Molecular Diagnostic Test (NAA)

Results

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

Specificity

This test detects the 2019 novel coronavirus strain (SARS-CoV-2). It was shown by the manufacturer by direct testing or in silico analysis to not cross-react with a large number of other bacteria and viruses.

Sensitivity

Limit of detection (LOD) : 1 x 10-2 TCID50/mL

Limitations

  • Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. 
  • Negative results 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. 

COVID-19 IgG (Serology)

COVID-19 IgG, Qualitative by CIA

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

This and other serology tests for COVID-19 have been evaluated by both the manufacturer and the 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. 

Performance of COVID-19 IgG, Qualitative by CIA
Antibody Performance Measure Estimate of Performance 95% CI

IgG

Sensitivity

100% (88/88)

95.8% to 100%

IgG

Specificity

99.6% (1,066/1,070)

99% to 99.9%

IgG

PPV at prevalence = 5%

92.9%

83.4% to 98.1%

IgG

NPV at prevalence = 5%

100%

99.8% to 100%

CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value

Data source:  https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance 

COVID-19 IgG by ELISA

This ELISA assay, developed by Euroimmun, detects IgG antibodies specific to the S1 domain of the spike protein of SARS-CoV-2. This test is reported as negative, indeterminate, or positive, and will include an index value.

This and other serology tests for COVID-19 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. 

 

Performance of COVID-19 IgG by ELISA
Antibody Performance Measure Estimate of Performance 95% CI

IgG

Sensitivity

90% (27/30)

74.4% to 96.5%

IgG

Specificity

100% (80/80)

95.4% to 100%

IgG

PPV at prevalence = 5%

100%

46% to 100%

IgG

NPV at prevalence = 5%

99.5%

98.6% to 99.8%

CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value

Data source: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/eua-authorized-serology-test-performance 

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.
  • 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 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.
  • Not for use in screening donated blood.
    References