A new study led by the National Institutes of Health (NIH) has revealed that routine clinical laboratory tests are unable to provide a reliable biomarker for diagnosing Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). The findings, from the NIH’s RECOVER Initiative, highlight the challenges in identifying consistent diagnostic markers for the condition, which affects millions worldwide.
The study, supported by NYU Langone Health, examined data from over 10,000 participants with and without prior COVID-19 diagnoses. Researchers analyzed 25 common laboratory tests, but found no single test or combination of tests that could reliably indicate previous infection, PASC, or specific PASC cluster types.
Challenges in Defining and Diagnosing Long COVID
One of the major roadblocks identified by the researchers is the inconsistent definition of PASC across different studies. This lack of a standardized definition makes it difficult to compare results and identify reliable biomarkers.
"This study is an important step toward defining long COVID beyond any one individual symptom," said study author Leora Horwitz, MD, director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC at NYU Langone. "This definition—which may evolve over time—will serve as a critical foundation for scientific discovery and treatment design."
The study also pointed out other potential factors contributing to the ambiguous results, including the selection of biomarkers, choice of comparison groups, duration of symptoms, types of symptoms, and patient population features such as sex, age, race, vaccination status, comorbidities, and severity of initial infection.
Implications for Future Research
The researchers suggest that future studies should focus on investigations beyond routine clinical laboratory tests, such as transcriptomics, proteomics, and metabolomics, to identify novel biomarkers.
"Understanding the basic biological underpinnings of persistent symptoms after SARS-CoV-2 infection will likely require a rigorous focus on investigations beyond routine clinical laboratory studies...to identify novel biomarkers," the study authors wrote in Annals of Internal Medicine.
David Goff, MD, PhD, director of the division of cardiovascular sciences at the NIH’s National Heart, Lung, and Blood Institute, emphasized the importance of rapid diagnosis for Long COVID. "Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible," he said. "Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key."
With approximately one in 20 US adults reporting persisting symptoms after COVID-19 as of June 2024, and 1.4% reporting significant limitations, the need for reliable diagnostic tools for Long COVID remains a critical public health priority.
