Blood Test Can Reliably Predict Patient Risk of Long COVID

Hospitalizations and deaths across the US may be down, but COVID-19 is here for the long haul—“long” being the operative word. A major nemesis in the post-pandemic world will be “long COVID,” also referred to as post-acute sequelae of COVID-19 (PASC), a condition in which infected patients experience symptoms months after infection ends. Accordingly, researchers and scientists have been hard at work to develop a laboratory test capable of accurately identifying a SARS-CoV-2 patient’s risk of long COVID. And now a team of researchers from the UK has offered new evidence suggesting that a test targeting blood-based biomarkers is capable of doing precisely that.  

The Diagnostic Challenge

While it usually takes about one to two weeks to recover from COVID-19, one in 13 adults in the US (7.5 percent) experience symptoms that linger for three or more months after they first contract the virus, according to the US Centers for Disease Control and Prevention (CDC). Up to now, there has been no reliable way to identify patients at greatest risk of long COVID.

Current laboratory tests assess long COVID risks by detecting antibodies that the body produces to combat the SARS-CoV-2 virus. However, antibody tests for PASC lack accuracy, missing an estimated 30 percent of cases involving patients who experienced only mild symptoms. In fact, there is no clear association between long COVID and severity of initial symptoms. People may suffer from long COVID even if they were completely asymptomatic. As a result, many victims never even took a PCR test confirming that they were infected with SARS-CoV-2 to begin with.

Bottom Line: While the worst of the pandemic may be behind us, long COVID cases are on the rise in the US and around the world, making the need for more effective PASC diagnostics more urgent.

The New Test

Among those working to respond to this need is a team of researchers from University College London. They set out to assess whether tests targeting proteins found in the blood would be a more effective way to determine a patient’s risks of developing long COVID.

Method: The researchers analyzed blood samples from 156 healthcare workers, 54 of whom had PCR-confirmed COVID-19 infection and 102 of whom were uninfected. The team performed weekly evaluation on participants using a questionnaire and PCR and serology tests for up to 16 weeks. Participants also completed follow-up questionnaires discussing their symptoms after six months and 12 months.

What the team wanted were blood-based biomarkers of long COVID. They monitored 91 different kinds of cytokine molecules generated by T cells to fight infection. Targeted mass spectrometry was used to analyze the blood of infected healthcare workers and identify protein signatures associated with the continued display of symptoms after six and 12 months. 

The Study Findings

The study, which was published in the Sept. 28 edition of the journal eBioMedicine, found that “more than 30 percent of individuals have persistent symptoms following acute SARS-CoV-2 infection.” Of equal significance, they also found a correspondence between the blood biomarkers and long COVID. Participants testing positive for SARS-CoV-2 had higher levels of 12 blood proteins (tied to cell adhesion and metabolic reprogramming) than the ones who tested negative. The higher the protein levels, the greater the correlation with symptom severity.

The researchers also concluded that abnormal levels of 20 blood proteins, most of which were linked to anti-coagulant (anti-clotting) and anti-inflammatory processes, in individuals that contracted SARS-CoV-2 within the previous six weeks were a reliable indication of whether they were likely to report COVID-19 symptoms a year after infection. This was the case even if the person’s initial symptoms were mild.

“Even mild or asymptomatic COVID-19 disrupts the profile of proteins in our blood plasma” in a way that may dramatically impact biological processes up to at least six weeks after infection," noted lead author Gabriella Captur, MD, PhD, in a press release.

Takeaway

While the researchers acknowledge that their findings must be verified in a larger, independent group of patients, the study provides new evidence supporting the possibility of developing a blood-based test for long COVID. The test could be administered alongside the PCR test used for initial diagnosis. Moreover, the long COVID test would not require massive new technology or ramp up. “The method of analysis we used is readily available in hospitals and is high-throughput, meaning it can analyze thousands of samples in an afternoon,” Captur stated in the press release.