The idiom “Herculean task” originates from 12 challenging labors that the hero Hercules performed as penance for the murder of his wife and children while under a spell. After expending ultimate effort on each, a new and more formidable one arose. Some of the greatest unsolved challenges of the COVID-19 pandemic relate to understanding, diagnosing, and treating long COVID. In their article, the investigators of the National Institutes of Health’s (NIH) RECOVER (Researching COVID to Enhance Recovery)-Adult cohort, with more than 10 000 participants, asked whether routine clinical laboratory tests aid in the diagnosis of long COVID (1). Alas, this effort could not find a definitive answer—more challenges remain.

Long COVID can present with any of dozens of symptoms, though the most common include fatigue, postexertional malaise, brain fog, gastrointestinal symptoms, dyspnea, and palpitations (2). The intensity of long COVID varies among individuals, changes over time, and may even contribute to death (3). When 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. Approximately 1 in 20 U.S. adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations (4). The incidence of long COVID is 3.5% among immunized people in the Omicron era (5), and it can occur after reinfection (6). The National Academies recently released a standard definition of long COVID for clinicians and researchers (7), and it remains a clinical diagnosis of exclusion.

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