Long COVID continues to evade diagnosis through lab tests
Dr. Kristine Erlandson (L), a professor of medicine and epidemiology at the University of Colorado Anschutz Medical Campus in Aurora talks with nurse Laura Petties. Photo courtesy of University of Colorado Anschutz Medical Campus
Blood and urine tests are ineffective for diagnosing long COVID — a constellation of long-term symptoms such as chronic pain, brain fog, shortness of breath and intense fatigue, a new study shows.
Without a clear tool to detect and treat the lingering illness, it remains “a major public health burden,” researchers noted, affecting millions of people worldwide and significantly altering quality of life.
The new study, funded by the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Initiative, was published Monday in Annals of Internal Medicine.
Because few large studies looked at standardized laboratory tests as a way to help diagnose long COVID, researchers decided to examine results of 25 measurements in more of than 10,000 adults enrolled in the RECOVER trial. Launched in 2021, this trial received $1.15 billion in congressional funding.
At the outset, participants underwent blood tests and were deemed eligible whether or not they had a previous infection of SARS-CoV-2.
Researchers followed them with surveys every three months and laboratory samples at six, 12, 24, 36 and 48 months after infection or the date of a negative test result.
In comparing responses to questionnaires and routine test outcomes, researchers assessed whether SARS-CoV-2 resulted in repeated laboratory abnormalities regardless if participants had symptoms.
The findings basically revealed little, said the study’s lead author, Dr. Kristine Erlandson, a professor of medicine and epidemiology at the University of Colorado Anschutz Medical Campus in Aurora. That’s because the laboratory results were inconclusive.
However, she and co-researchers recommended in their study report that clinicians still perform routine clinical tests to rule out other treatable causes of the symptoms in post-acute sequelae of COVID-19, the scientific name for long COVID.
Researchers also uncovered evidence to bolster the notion that SARS-CoV-2 could contribute to the risk of diabetes independent of long COVID — a link found early in the pandemic.
Individuals with prior SARS-CoV-2 also had higher urine albumin to creatinine ratio. This indicator of early kidney disease has shown an association with cardiovascular conditions in other populations.
Continuing inflammation may be a possible explanation for smell and taste disruptions and post-acute sequelae of COVID-19, researchers said.
“The diversity of symptoms may be one of the reasons that we have difficulty in truly understanding why some people develop long COVID and ultimately how we can treat it,” Erlandson said.
“Long COVID is a condition currently defined by symptoms and physical exam findings, not by abnormal routine laboratory measures,” she added.
“Similarly, providers should certainly not dismiss a diagnosis of long COVID based on normal clinical laboratory values.”
In an accompanying editorial, researchers from Johns Hopkins University School of Medicine in Baltimore noted that most significant unsolved enigmas of the COVID-19 pandemic pertain to the knowledge, diagnosis and treatment of long COVID.
“When [it is] severe, long COVID can be disabling, resulting in job loss or inconsistent ability to perform other roles, such as caregiving. Even in 2024, long COVID remains common,” Drs. Paul Auwaerter and Annukka Antar wrote in the editorial.
“Approximately 1 in 20 U.S. adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations The incidence of long COVID is 3.5% among immunized people in the Omicron era, and it can occur after reinfection.”
The editorial’s writers added that “importantly, acknowledging symptoms with empathy and creating a symptom management plan provides a basis for trust and hope amidst uncertainty.”
It’s impressive that researchers undertook “a high-quality analysis” of 25 routinely available labs in an attempt to help diagnose long COVID, said Dr. John Baratta, founder and co-director of the UNC COVID Recovery Clinic at the University of North Carolina-Chapel Hill School of Medicine. He was not involved in the study.
“The study did not show clinically meaningful changes in the blood work between people who have long COVID and those who do not,” said Baratta, a specialist in physical and rehabilitation medicine.
“This is unfortunate, but not surprising, as many of us clinicians treating people with long COVID have been unable to find abnormalities on extensive medical workups.”
The study “continues to show how difficult it can be to diagnose someone with long COVID,” said Dr. Amy Edwards, an infectious disease specialist who heads the Pediatric COVID Recovery Clinic at University Hospitals Rainbow Babies & Children’s Hospital in Cleveland.
Arriving at a diagnosis of long COVID involves taking a detailed medical history and doing a thorough physical exam, Edwards said.
“Currently, physicians have to rule out everything else — what we call a diagnosis of exclusion — rather than being able to positively diagnose someone based on a definite blood result,” she said.
Despite the researchers’ findings, Edwards added that researchers should pursue these types of studies “until a clear idea of what causes long COVID is known, so that a test can be developed to make diagnosis easier.”
She pointed out that this study didn’t include children, so clinicians remain unaware if the same results would apply to pediatric patients.
Dr. Ziyad Al-Aly, a clinical epidemiologist at Washington University School of Medicine in St. Louis, said he appreciates that the researchers made an earnest attempt to study lab abnormalities in hopes of identifying diagnostics for long COVID.
“You won’t catch any fish if you don’t have your line in the water,” Al-Aly said, adding, “If we don’t do this as a community of scientists, we’re never going to make progress. It’s good that they tried.”
For now, the lack of abnormal findings in blood tests may complicate long COVID patients’ approval process for disability benefits, Baratta said.
“Long COVID is an extremely complex process that reaches beyond the boundaries of current medical knowledge,” he said.
“However, there is hope for the future. There are tremendous research efforts underway globally to uncover the mysteries of this disease.”