COVID-19, the infection spread from the SARS-CoV-2 virus, is an unusual disease with unique characteristics.
In most people, symptoms do not present for days after initial infection. In some, symptoms are so mild that they appear to be other common, passing respiratory disturbances — such as seasonal allergies, or a cold. Studies suggest that people can continue to carry the virus for days or weeks after symptoms disappear—though their capacity to infect others at this stage is unknown.
There is evidence, too, that on re-testing, people who have tested negative previously for SARS-CoV-2 are testing positive again. Recent news from South Korea suggests that patients who test positive after previous negative tests aren't infectious, however.
According to a report in JAMA, a small group of patients with COVID-19 in China who met criteria for hospital discharge or discontinuation of quarantine—including two negative real time reverse transcription polymerase chain reaction (RT-PCR) test results—had positive RT-PCR test results 5 to 13 days later.
This suggests that at least a minority of recovered patients may continue to shed virus in their respiratory tracts, although as noted previously – whether this represents infectious virus is unknown. A nuclear-derived method for detecting genetic material from pathogens, real time RT-PCR is the most widely used assay for COVID-19. However, several small studies of patients with COVID-19 have shown live virus able to be cultured from respiratory specimens only out to 8 or 9 days, despite much more prolonged viral genetic material detection in RT-PCR based assays of respiratory specimens.
A Path Forward
The potential for the continuing spread of SARS-CoV-2 may prove to be a challenge as the communities served in and around the Philadelphia-area begin a cautious effort to move beyond sheltering at home.
In the weeks and months ahead, the safety of individuals returning to the workplace and public spaces will be of paramount concern.
There are currently two types of tests for SARS-CoV-2:
- The first involves molecular detection (RT-PCR) of viral genetic material (a nasal swab or saliva sample) for acute diagnosis of COVID-19. RT-PCR-based testing can diagnose acute infection with COVID-19. However, as noted earlier; some patients with COVID-19 infection can have prolonged shedding of viral genetic material (out to several weeks past symptom resolution) that can be detected by PCR based testing, and how this relates to prolonged infectivity is unknown.
- The second test is used to determine the presence of an adaptive immune response to SARS-CoV-2 rather than the presence of the virus in individuals who may have been exposed to the virus.
These serologic immunoassays are not for diagnosis, but are very useful as a means of establishing the efficacy of diagnostic tests, tracking the potential spread of the virus within a community, vaccine development and perhaps, the creation of novel treatments for COVID-19.
Antibody Testing for COVID-19 at Penn
Penn Medicine recently began serologic testing using an advanced chemoluminecent microparticle SARS-CoV-2 antibody immunoassay from Abbott Laboratories, which has an Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA).
Established guidance on the use of this assay at Penn Medicine mandates that the test not be used for diagnostic use, according to David A. Pegues, MD, Medical Director of Healthcare Epidemiology and Infection Control at the Hospital of the University of Pennsylvania.
“At the current time, there are no guidelines from the FDA, CDC, or PA Department of Health about the use of antibody testing for individual patient management during the COVID-19 epidemic,” Dr. Pegues explained. He added that a positive antibody test should not be interpreted as evidence of protective immunity at this time.
What is the Abbott SARS-CoV-2 IgG Immunoassay?
The Abbott SARS-CoV-2 IgG Assay is a test that measures human SARS-CoV-2 IgG antibodies generated as part of the adaptive immune response to COVID-19.
The primary serum antibody (75%) in the blood; immunoglobulin G (IgG) binds to specific antigens on the surface of foreign particles in the blood — bacteria, viruses and other invaders — to prime them for phagocytic recognition and ingestion. In so doing, IgG creates recognizable antibodies unique to a specific disease.
The presence of these unique antibodies indicate that a person has been exposed to, and had an immune reaction, to the disease. A key facet of the SARS-CoV-2 IgG Assay is its use of chemiluminescence, an immunoassay technique that has the benefit of ultra-sensitivity to detect small amounts of a biological molecule.
In a chemiluminescent immunoassay (CLIA), the indicator of the analytic reaction is a luminescent molecule that reacts to emit visible or near-visible radiation in the form of light. This reaction can then be measured as a relative light unit (RLU). There is a direct relationship between the amount of IgG antibodies to SARS-CoV-2 in a sample and the RLU detected by the assay system optics.
The SARS-CoV-2 IgG Immunoassay
Serolic antibody testing will be important in understanding the future scale of the pandemic and to detect seroconversion following vaccination when a vaccine becomes available.
For practical use, the SARS-CoV-2 IgG Assay can be used to detect COVID-19 in persons whose viral load is below the detection limit for reverse transcription polymerase chain reaction (rRT-PCR) nasal swab tests.
The test can also be used to identify convalescent plasma donors and to perform epidemiological studies of COVID-19 prevalence in a community. A new, two-part research initiative on convalescent plasma therapy for COVID-19 patients is now underway in the Division of Infectious Diseases and the Division of Transfusion Medicine and Therapeutic Pathology at Penn Medicine.
How accurate is the Abbott Assay?
The test’s capacity to correctly identify non-infected persons appears to be approximately 99%.
According to Abbott validation studies, the SARS-CoV-2 IgG assay correctly identified infection in 25% of individuals from 3-7 days after onset of symptoms, 86% of those between day 8-13, and ~100% after 14 days.
Validation studies at Penn Medicine performed on serum samples from patients are consistent with those from Abbott performance data.
Using patient serum samples collected at least 14 days after a positive SARS-CoV-2 molecular test, there was 98% agreement with molecular results. Penn researchers observed approximately 99% specificity in pre-COVID-19 era banked serum samples.
Additional validation studies are currently in progress to further verify the specificity of the assay using sera from patients with non-SARS-CoV-2 coronavirus infections.
Additional Resources from Penn Medicine