New Institutes of Health Study Suggests ‘Long COVID’ May Not Exist

A health worker takes a swab sample from a woman to be tested for the COVID-19 coronavirus at a swab collection site in Beijing, China, on May 3, 2022. NOEL CELIS/AFP via Getty Images

People who report symptoms of a medical condition known as “long COVID,” particularly women, may actually be suffering from depression and anxiety, a new study by the National Institutes of Health (NIH) suggests.

Researchers based their findings on 309 participants enrolled within a 100-mile radius of Bethesda, Maryland. Of the total sample, 180 people had a previous COVID-19 infection with mild to moderate symptoms that did not require hospitalization; the study also enrolled 122 control participants who never had the illness.

It found that participants from the COVID-19 group reported more physical symptoms associated with long-haul COVID-19 (PASC) than those in the control group. These symptoms included fatigue, difficulty concentrating, headache, memory impairment, insomnia, chest discomfort, and anxiety.

The NIH conducted the study between June 30, 2020, and July 2021. The study’s findings appear in the May 24 “Annals of Internal Medicine.”

Researchers administered individual surveys to screen for mental health issues, such as anxiety and depression. A total score of 3 or higher was the recommended cutoff on each measure to warrant further evaluation.

‘Long-Haulers’ Show Higher Anxiety

The study found that the proportion of participants with generalized anxiety scores above the cutoff was “significantly higher”—14 percent versus 3 percent—in the COVID-19 group than in the control group.

In the COVID-19 group, the risk factors for developing PASC were “female gender and pre-COVID-19 history of anxiety.”

“Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants [with COVID-19]” to provide a physical basis for PASC.

“A high burden of persistent symptoms was observed in persons after COVID-19. An extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.”

Adult participants with lab-confirmed COVID-19 prior illness were eligible if they were at least six weeks past the onset of symptoms, had no fever within seven days before enrollment, and did not have worsening respiratory issues.

Both groups were required to perform a negative PCR test at the screening visit and report 17 specific symptoms.

The study found “no significant differences” in neurocognitive testing scores between the two groups. However, despite the essentially normal findings on objective testing, “the presence of PASC had a significant effect on self-reported physical and mental health.”

“Participants with PASC reported lower quality of life than either participants with COVID-19 without PASC or control participants, as measured by the mental and physical health components of the [surveys].”

Of the potential pre-COVID-19 risk factors, “only female gender and self-reported history of anxiety were significantly associated with increased risk for [PASC].”

The study suggests that post-COVID-19 anxiety may reflect in “uncertainty and worry felt by those experiencing persistent unexplained symptoms.”

“The constellation of subjective symptoms in the absence of objective abnormalities on diagnostic evaluation resembles what has been described with other illnesses, including chronic fatigue syndrome,” and mental health disorders such as depression and anxiety.

Study Reveals Limitations

While the research found that self-reported anxiety was “significantly associated with PASC,” the study has several limitations.

“First, most participants with COVID-19 in our study had mild to moderate initial illness that did not require hospitalization,” according to the report. “Thus, our findings may not represent the full spectrum and severity of PASC experienced by persons with severe disease requiring hospitalization.

“Second, although we enrolled participants regardless of the presence of PASC, our study probably overestimated the prevalence of persistent post-COVID-19 symptoms because persons with PASC were likely more motivated to enroll.

“Third, control participants were not intentionally age or gender-matched to participants with COVID-19. Fourth, PASC that resolved before the study enrollment were not captured in our cohort.

“Finally, this report contains detailed data on 189 COVID-19 survivors, a sample size that may not fully capture all of PASC.”

The Division of Intramural Research at the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and NIH provided funding for the study.

The report concluded that the source of PASC remains unclear and requires further study.