Targeted Testing for COVID-19: Diagnostic, Immunologic, or Both?

Why Targeted Genomics has decided to offer COVID-19 antibody testing.

 Our COVID-19 test offering is IgM, IgG antibody-based and validated in a high-complexity laboratory. All COVID-19 testing should be performed in CAP/CLIA certified laboratories.

As next generation sequencers across the globe turned to mapping the biology of the novel coronavirus SARS-CoV-2 in the early months of 2020 it became clear to Targeted Genomics our corner of the lab testing world was about to change dramatically in ways we never imagined.

Our core mission, to bring a targeted approach to assisting those affected by the “silent epidemic” of celiac disease(1) requires us to balance clinical and lifestyle considerations in designing the testing we offer our clients. We now face a devastating and “hardly silent pandemic” at the hands of a novel submicroscopic enemy. The challenge is on a global scale as is the fight back. Here we offer our unique perspective to the question of whether to use diagnostic RNA-based or immunologic antibody-based testing for the SARS-CoV-2 virus.

The emergence of this viral “piece of bad news wrapped in protein”(2) has strained the resources and ability of clinical laboratories around the world to expedite diagnosis of acute illness while identifying immunologically protected individuals who might safely return to the workforce. With time a precious commodity the question was where to focus our efforts. Targeted laboratory testing can give much needed understanding of the virus, the disease it causes, and implications for human beings. However, before performing any clinical laboratory test it is essential to clarify the question being asked and how the answer will positively impact disease outcome.

For COVID-19, laboratory testing falls into two broad categories: diagnostic and immunologic.

  • Diagnostic testing asks the question: Do you have the virus that causes COVID-19 in your cells?
  • Immunologic testing asks the question: Are you developing, or have you already developed immunity to the virus that causes COVID-19?

It is critical to understand the questions being asked by both tests. Are we diagnosing disease, identifying immunologically protected individuals, or both?

Diagnostic testing looks for acute viral infection through swabbing of upper respiratory cells lining the individual’s nose and throat. The target of the test is viral (not human) RNA and a positive test confirms active infection. Currently most diagnostic viral RNA testing is performed in individuals whose symptoms are consistent with COVID-19. A positive test confirms the disease while a negative test is interpreted in context of the disease symptoms. False negatives can occur if virally infected cells are not represented in the collected sample.

Immunologic testing, commonly called antibody testing, screens for current or past COVID-19 viral infection using a blood sample. The target of the test is host protein antibodies made against the virus during early infection (IgM) and post-infection antibodies (IgG.) During acute infection IgM antibodies can help confirm disease in a symptomatic individual even when there was a false negative from the viral RNA diagnostic test. However, in a previously infected individual who has recovered from COVID-19, IgM antibodies are replaced by IgG. Therefore, immunologic testing ideally includes both IgG and IgM.

As the immediate crisis stabilizes, the focus will likely shift from diagnosing acutely infected individuals in favor of searching for the immunologically protected. As an example there are a growing number of healthcare workers previously infected with COVID-19, now IgG positive, recovered, and back on the front lines caring for patients. Growing evidence points to a significant unidentified IgG positive percentage of the world population who could potentially return to work already immune to COVID-19.

With a decreasing number of symptomatic individuals and an increasing population of those who are ready, willing, and able to return to the workforce, immunological testing will give the most expedient answers to the most pressing questions: Have you ever been infected, and are you now immunologically protected to go back to work?

Actionable laboratory results have always been the core mission of Targeted Genomics and we hope widespread immunologic testing will give individuals and policymakers more information for the difficult decisions ahead. When and how to return to work may be as much an individual as a policy decision in the coming months and we hope the insights gained through COVID-19 antibody testing will provide new understanding in the fight against the virus providing new ways to win the battle.

References

  1. Green, Peter H.R. Celiac Disease: A Hidden Epidemic. New York: Harper Collins Publishers, 2006, 2010, 2016.
  2. Corum, Johnathon and Zimmer, Carl. Bad News Wrapped in Protein: Inside the Coronavirus Genome. The New York Times. April 3, 2020. (make live link)

For updated COVID-19 numbers please visit the CDC website by clicking here.