Why Can’t We Test for Long COVID? Unraveling the Diagnostic Puzzle

Of 25 routine clinical lab tests, not one can aid in diagnosing post-acute sequelae of SARS-CoV-2 (Long COVID).

Over 10,000 participants were analyzed in a study to explore Long COVID’s clinical markers and health implications. Results indicated no effective laboratory markers for PASC, but suggested connections between prior SARS-CoV-2 infections, heightened diabetes risk, and early signs of kidney disease.

A national cohort study of adult participants with and without prior SARS-CoV-2 infection found that there are no objective tests to accurately diagnose post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. Data also suggested that many of the long-term PASC symptoms are due to ongoing inflammation, rather than viral invasion of the affected area. The findings are published in Annals of Internal Medicine.  

Findings from the RECOVER Trial

Researchers from the National Institutes of Health studied more than 10,000 adult patients enrolled in the RECOVER (Researching COVID to Enhance Recovery) trial to investigate clinical laboratory markers of SARS-CoV-2 and PASC. Because a baseline was necessary to compare variables, adults were eligible to participate in the study regardless of prior infection of SARS-CoV-2. The researchers compared questionnaire responses and routine clinical laboratory results from participants to determine if SARS-CoV-2 led to persistent laboratory abnormalities, whether or not symptoms were present.

The researchers found that none of the 25 routine clinical laboratory values assessed in the study could serve as a clinically useful biomarker of PASC. Additionally, they found evidence to support the idea that SARS-CoV-2 may contribute to diabetes risk independent of PASC symptoms, a connection that had been made early in the pandemic. Those with prior SARS-CoV-2 also had higher urine albumin to creatinine ratio, a marker of early kidney disease that has been associated with cardiovascular disease in other populations. The data also showed that ongoing inflammation is a potential mechanism underlying anosmia (smell/taste disturbances) and PASC.

Editorial Insights on Long COVID Challenges

The authors of an accompanying editorial from Johns Hopkins University say that some of the greatest unsolved challenges of the COVID pandemic relate to understanding, diagnosing, and treating long COVID. Extremely large observational studies like RECOVER are a once-in-a-lifetime opportunity to study an infection-associated chronic illness that occurred simultaneously in millions triggered by the same pathogen. The findings are a reminder that physicians should consider long COVID in differential diagnoses for symptoms or conditions without apparent etiology.

Reference: “Standard Clinical Laboratory Measurements Do Not Differentiate Prior SARS-CoV-2 Infection and Postacute Sequelae Among Adults in the RECOVER Cohort” 12 August 2024, Annals of Internal Medicine.
DOI: 10.7326/M24-0892