For millions of people worldwide, COVID-19 brought a lasting burden of puzzling symptoms that can be difficult to manage. Patients began warning about what became known as long COVID in 2020, prompting scientists to investigate its causes and search for treatments.

Progress has followed, but major questions remain unresolved. Researchers continue to debate which symptoms should fall under the long COVID umbrella and how directly some reported health problems can be attributed to SARS-CoV-2 infection.

Some patients who initially experienced severe COVID-19 are living with organ damage caused by their illness. Others developed debilitating chronic effects after comparatively mild infections, and those symptoms have proved much harder to explain.

A recent study published in PNAS intensified that debate by analyzing health insurance claims involving 245 million patients in the United States. Its findings questioned whether many symptoms attributed to long COVID were actually caused by SARS-CoV-2 infection.

“This study does not indicate that symptoms beyond one year are not genuine but that their attributability to COVID-19 is uncertain,” the authors concluded.

Epidemiologist Gideon Meyerowitz-Katz also discussed the findings on his Substack. He wrote, “it seems to me that there are a small number of long-term issues that COVID-19 causes – particularly fatigue, anosmia (lack of sense of smell), and respiratory issues – and many of the other things that have been attributed to the virus are probably caused by something else.”

Other researchers have proposed that long COVID may not be a unique condition. Instead, they have suggested it could be another manifestation of post viral syndromes that have been documented after numerous other infections.

Whatever the underlying cause, researchers broadly recognize that patients’ symptoms are real. A newer study published in Annals of Internal Medicine now offers hopeful evidence that substantial improvement and complete symptom remission are possible for many people over time.

The research assessed more than 1,000 adults with long COVID. By the three year mark, half of the group had experienced sustained improvement in their symptoms, while more than a quarter had reached complete symptom remission.

All participants were part of the RECOVER-Adult trial, a large study funded by the National Institutes of Health. The trial enrolled volunteers at 83 locations across the United States and Puerto Rico.

Participants had been identified as likely long COVID patients 12 months after their initial infections. They reported a wide variety of symptoms, including fatigue and the loss of smell and taste, which are widely associated with COVID-19.

The reported symptoms also included more contentious problems such as depression, anxiety, vision difficulties, and bladder issues. Researchers divided the patients into five subgroups based on the different combinations of symptoms they reported.

The participants completed regular surveys as researchers followed them over time. Those responses allowed the research team to track whether their symptoms were improving and whether those changes were sustained.

At the two year assessment, 36.2% of patients had experienced sustained symptom improvement. By the three year assessment, that figure had risen to 50.1%, indicating that improvement continued for a sizeable portion of the cohort.

At three years, 56.4% of participants said their symptoms had decreased and their quality of life had improved. At that same point, 26.9% had experienced complete remission of their symptoms.

The researchers said the results could help shape future clinical trials because they show “a sizeable proportion of persons with prevalent likely [long COVID] exhibit some symptom reduction over time.”

The next challenge is determining whether potential treatments can relieve long COVID symptoms independently of the natural recovery trajectory observed in the study. That distinction will be important when researchers evaluate whether an intervention is producing benefits beyond improvement that might have occurred over time.

The findings also align with Meyerowitz-Katz’s interpretation of the earlier PNAS research. He wrote, “this implies that COVID-19 may cause far fewer long-term issues than previously thought and that those issues may resolve much more quickly than we believed.”

Even with these encouraging results, millions of people continue to report debilitating symptoms that they attribute to long COVID. Further research into the causes and potential treatments remains important, while COVID-19 itself continues to circulate as a disease.

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