Postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, has been reported in millions of people worldwide and is a major public health burden. It is also a difficult problem for workers’ compensation claim administrators who have long COVID claims to adjust.
According to NIH-backed researchers writing in Annals of Internal Medicine “PASC” is generally accepted as an umbrella term encompassing a wide spectrum of symptoms and health conditions that persist after acute SARS-CoV-2 infection, resulting in a major impact on quality of life. Although potential models of pathogenesis have been postulated, including immune dysregulation, viral persistence, organ injury, endothelial dysfunction, and gut dysbiosis, there are currently no validated clinical biomarkers of PASC.
As part of the National Institutes of Health’s RECOVER (Researching COVID to Enhance Recovery) Initiative, the researchers previously examined prospectively collected data from nearly 10,000 people in the RECOVER-Adult cohort with and without SARS-CoV-2 infection and identified 12 symptoms that best distinguish those with prior infection from those who are uninfected. They developed a PASC index based on these 12 symptoms, with 23% of the cohort with prior SARS-CoV-2 infection meeting this research threshold.
They further identified multiple clusters or subphenotypes of PASC. This framework does not encompass all people experiencing PASC but permits exploration of clinical laboratory features among those meeting the PASC threshold.
Routine clinical laboratory tests that accurately distinguish people with PASC from those without PASC might be useful in the diagnosis, prognosis, prevention, and treatment of PASC or its subtypes. Laboratory tests might also identify those who have persistent organ damage but minimal or no symptoms.
Studies have found potential biomarkers associated with PASC using mostly research-focused assays, but results have been inconsistent, perhaps due to different PASC study definitions; use of only selected biomarkers; choice of comparison groups, if any (people who have recovered from PASC or healthy control participants); duration of symptoms; types of symptoms or phenotypes; and patient population features, such as sex, age, race, vaccination status, comorbidities, and severity of initial infection.
Early small-cohort studies failed to find routine clinical biomarkers. There is a paucity of large studies examining the utility of standardized laboratory tests obtained in routine clinical care. For these reasons, these researchers decided to investigate clinical laboratory markers of SARS-CoV-2 and PASC.
Accordingly, the researchers conducted a study to determine whether SARS-CoV-2 infection led to persistent changes in results of common clinical laboratory tests, regardless of symptoms, in people with prior infection compared with those without prior infection. If so, laboratory studies could be used to augment symptom-based definitions of PASC.
The researchers analyzed 25 routinely used and standardized laboratory tests that were selected on the basis of availability across different institutions, prior literature, and clinical experience. These tests were prospectively done in Clinical Laboratory Improvement Amendments (CLIA) – certified laboratories with samples from 10,094 RECOVER-Adult participants representing a diverse cohort from across the United States.
Unfortunately overall, “no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC,or the specific type of PASC cluster.”
“In summary, our findings suggest that even highly symptomatic PASC may have no clinically observable objective findings on routine laboratory testing. 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 (for example, transcriptomics, proteomics, metabolomics) to identify novel biomarkers.”