Long COVID remains an elusive condition with no reliable diagnosis

In recent times, the medical world has faced an unprecedented challenge: the diagnosis and treatment of a condition now largely referred to as long COVID.

Characterized by a myriad of symptoms that linger well beyond the initial SARS-CoV-2 infection, it presents a puzzle for doctors worldwide.

Emerging research suggests routine laboratory tests may fall short in pinning down this elusive illness, highlighting the complexity of identifying and diagnosing long COVID.

“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.”

Symptoms of long COVID

Long COVID encompasses a wide spectrum of symptoms and health conditions that persist for months or years after infection from SARS-CoV-2, the virus that causes COVID-19.

The signs of long COVID vary widely, affecting multiple organ systems. Common symptoms range from mild to debilitating, including fatigue, shortness of breath, cough, or difficulty breathing.

People with long COVID also experience cognitive difficulties such as trouble concentrating, memory issues, or confusion. 

Severe headaches, chest pain, aching muscles, sleep problems, and gastrointestinal issues are also reported by long COVID patients.

The long COVID enigma

Despite tireless research, no validated clinical biomarkers for long COVID have been identified to date, making the diagnostic process intricate.

Currently, it demands a comprehensive medical history, a thorough physical examination, and extensive lab work to eliminate other potential causes.

The study in focus is part of NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative. The primary goal is to determine whether individuals with a prior SARS-CoV-2 infection had distinct changes in biomarkers, such as platelet counts or protein in the urine, compared to those without a prior infection.

The RECOVER study

More than 10,000 adults were enrolled in the RECOVER Adult Cohort at 83 sites across the United States between October 2021 and October 2023.

The cohort is demographically diverse, with participants from various geographic locations, including some who had never contracted the virus.

Among the 8,746 participants with a prior SARS-CoV-2 infection, many were exposed to different variants of the virus.

Study participants underwent a baseline regimen of surveys, physical examinations, and 25 standard lab tests, followed by periodic surveys and lab work throughout the two-year study.

The lab tests included a complete blood count panel, metabolic panel, hemoglobin A1c (HbA1c), urinalysis, and urine albumin to creatinine ratio (uACR), among others.

Few variations in biomarkers

Despite the vast range of testing, the lab results showed few significant variations in biomarkers between those with prior infection and those without.

Notably, prior infection was associated with modest increases in HbA1c, a measure of average blood sugar levels over two to three months, though these increases disappeared after excluding people with pre-existing diabetes.

Another intriguing find was a minor rise in uACR, a measure of low kidney function, among those previously infected. However, this was observed in only a small subset of participants, suggesting it could be a result of the severity of their initial infection.

Ongoing efforts to decipher long COVID

In a further analysis, researchers compared individuals who developed long COVID with those who did not within the infected group.

Using a long COVID index that highlighted twelve symptoms typically identifying people with long COVID, the experts found no significant differences in lab test results between the two groups.

But as with any complex phenomenon, the research continues. Dr. Kristine Erlandson is a professor in the Division of Infectious Diseases at the University of Colorado Anschutz Medical Campus.

“Future work will use RECOVER’s biobank of cohort samples such as blood and spinal fluid, to develop more novel laboratory-based tests that help us better understand the pathophysiology of long COVID,” said Dr. Erlandson.

Thus, while the mystery of long COVID diagnosis remains largely unsolved, the relentless pursuit of understanding it better continues, offering hope to those grappling with this enigmatic condition.

The study is published in the journal Annals of Internal Medicine.

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