Study highlights that many long-term symptoms may result from ongoing inflammation rather than persistent viral presence.
Kristine M Erlandson, MD, MSc, is a professor of medicine, specializing in infectious disease, at the University of Colorado School of Medicine.
Image credits: University of Colorado School of Medicine
A national cohort study has determined that routine laboratory tests are not effective for diagnosing post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. The study suggests that many long-term symptoms of Long COVID are likely due to ongoing inflammation rather than persistent viral presence.1
Among 10,094 participants, those with prior SARS-CoV-2 infection had slightly lower platelet counts, higher HbA1c levels, and higher urinary albumin–creatinine ratios compared to uninfected participants, but these differences were clinically modest. The difference in HbA1c diminished when excluding those with preexisting diabetes. There were no significant differences in lab values between participants with high and low PASC indices among those with prior infection.1
Researcher on this study, Kristine M Erlandson, MD, MSc explains to Contagion reasoning behind chosing the 25 lab values, “These tests were selected on the basis of their routine availability and standardized use across CLIA (Clinical Laboratory Improvement Amendments)-certified laboratories, prior literature, and clinical expertise of the RECOVER investigators. Many laboratory values were not included as part of RECOVER that might be evaluated by providers, including other inflammatory markers, lymphocyte subsets, cortisol or other hormone markers.”
An editorial from Johns Hopkins University that accompanied the study highlights the ongoing challenges in understanding, diagnosing, and treating Long COVID. It underscores the unique opportunity provided by large-scale studies like RECOVER to explore this chronic condition linked to a widespread pathogen affecting millions. The editorial emphasizes the importance of considering Long COVID in differential diagnoses for unexplained symptoms or conditions.1
The study also found that SARS-CoV-2 infection might elevate the risk of diabetes independently of Long COVID symptoms, a link observed earlier in the pandemic. Participants with a history of infection exhibited higher urine albumin-to-creatinine ratios, suggesting early kidney disease, which is associated with cardiovascular issues in other populations. Additionally, ongoing inflammation might affect symptoms like anosmia (disturbances in smell and taste).1
Although, these changes were not significant enough to act as diagnostic markers for Long COVID. A limitation is that it could not be determined whether the differences in laboratory markers are consequences of or risk factors for SARS-CoV-2 infection.2
Erlandson discusses the study’s finding that no routine lab values are useful for diagnosing PASC, and what clinicians should do to identify and manage patients with suspected Long COVID effectively, “A long COVID diagnosis should be based on a detailed history and physical to understand a patient’s symptoms and physical exam findings, in relation to COVID infection.Routine laboratory work can rule outother easily treatable causes, but the diagnosis is really symptom-based.”
Future research will utilize RECOVER’s biobank of cohort samples to develop more effective laboratory tests and better understand Long COVID's pathophysiology.2
The RECOVER Initiative is conducting eight clinical trials to test 13 potential treatments for Long COVID. Key trials include:3
In summary, the study found that routine laboratory tests are not effective for diagnosing Long COVID. Analysis of 25 common lab values showed no reliable biomarkers for the condition, which appears more closely related to ongoing inflammation than persistent viral presence. Accurate diagnosis should rely on detailed patient history and symptom assessment.
