Testing for lesser known antibodies produces a better COVID-19 test

Most antibody tests look for responses to SARS-CoV-2's spike protein, but more accurate results include antibodies against the virus's other proteins

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Two medical workers take a COVID-19 swab test

H Shaw via Unsplash

Before we can go back to a somewhat “normal” state, many scientists say we need widespread testing and contact tracing—but how effective is our current testing system? 

To determine if someone currently has COVID-19 we test for the presence of the virus. To determine if someone was previously infected, we test for the antibodies their body produced in response to the infection. These antibodies usually specifically target the COVID-19 spike protein—an appendage that helps the virus enter human cells. 

Many caution against the accuracy of COVID-19 tests as studies show a growing number of false negative results from infected individuals with milder symptoms. A paper published recently in Nature outlines that analyzing antibody responses to the lesser studied, nonstructural COVID-19 proteins—proteins of unknown function—answer this diagnostic problem.

These researchers measured levels of antibodies targeting various COVID-19 proteins in the blood of infected and uninfected individuals. Results showed that analyzing the combined antibody response to the presence of two specific nonstructural proteins, called ORF8 and ORF3b, produced results that were 73 percent more accurate than testing for all spike protein antibodies. 

ORF8 and ORF3b antibody levels were most constant across infected participants from 1 to over 30 days after the onset of symptoms. This suggests that, unlike the current spike protein antibody test, diagnostic tests looking at ORF8 and ORF3b antibodies are ideal for diagnosing individuals with current or past COVID-19 infections.  

COVID-19 testing previously ignored nonstructural SARS-CoV-2 protein antibodies. But now these have clear potential to replace current diagnostic targets. More accurate testing will allow for both the public and public health experts to better understand the spread of the virus so that they can work together to contain this destructive pandemic.