A new study by the National Institutes of Health (NIH) highlights the difficulty of finding a lab test for long Covid – a novel condition that encompasses dozens of symptoms and is currently considered a “diagnosis of exclusion”.
Long Covid’s most common symptoms include brain fog, fatigue and heart palpitations, which can change over time and be disabling when severe. Approximately one in 20 adults reported persistent symptoms of Covid, as of June 2024.
The study followed patients for four years and included a battery of standard lab tests, but found “markedly few” differences between people who had long Covid and those who did not.
“Covid is just the latest example of an infectious disease that can cause a post-infectious fatigue syndrome,” Dr Paul G Auwaerter, a professor of medicine and director of the division of infectious diseases at Johns Hopkins University School of Medicine and a Lyme disease researcher.
This study focused on one of long Covid’s key mysteries – finding a “biomarker” that could help doctors develop a diagnostic test, rather than rule out other possible illnesses as they do today.
“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,” said Dr David Goff, director for the division of cardiovascular sciences at the NIH’s National Heart, Lung and Blood Institute.
“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.”
The research, published in the Annals of Internal Medicine, looked at more than 10,000 adults across 83 clinical sites in the US between 2021 and 2023. About 1,800 participants met researchers’ definition for long Covid.
Participants received a panel of 25 standard blood and urine tests in the study beginning either six months after infection or when they enrolled. They were followed for four years. Like other long Covid studies, the majority of participants were middle-aged women. The group was considered racially diverse.
Scientists found few differences between people diagnosed with long Covid and those who did not meet the criteria. Researchers found a modest association with HbA1c, a measure of average blood sugar over two to three months, but the association disappeared when they controlled for pre-existing diabetes.
Similarly, they considered a test that showed slightly lower kidney function for some participants, but the metric appeared in only a minority of patients and may have resulted from initial Covid-19 infection.
Part of the challenge to finding or developing a long Covid lab test, said Auwaerter, was scientists still do not understand the mechanisms underlying chronic fatigue syndromes in general. Especially those, like Covid, that “preferentially [affect] women in middle age”. That makes finding a diagnostic test, “even greater as a challenge”. Auwaerter called the task “herculean” in an editorial accompanying the new study.
One key difference in the research space is funding. The suite of Recover studies now under way, including ambitious and large-scale efforts studying electronic health records, autopsies and large observational studies, are all paid for with a $1.1bn budget from Congress. More funding will probably be necessary if society wants further advances.
“The hunt will go on,” said Auwaerter, and probably move to tests that are currently used only for research, to see if they “could shed some light or offer clinicians a diagnosis”.
