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Long COVID cognitive research needs better studies, an international task force urged.

The approach to assessing cognitive dysfunction after SARS-CoV-2 infection requires an overhaul to better understand long COVID prevalence, trajectory, mechanisms, phenotypes, and psychosocial factors, said experts from the NeuroCOVID International Neuropsychology Taskforce.

"As one of the most common symptoms of post-COVID-19 condition and one for which affected individuals may seek accommodations and disability benefits in accordance with the Americans With Disabilities Act, it is imperative that we use more rigorous studies of cognitive outcomes," wrote task force member Sara Weisenbach, PhD, of McLean Hospital and Harvard Medical School in Boston, and co-authors, in a viewpoint paper published in .

Long COVID cognitive dysfunction, including "brain fog," can affect even relatively young people and can last for months. A modeling study based on 1.2 million COVID patients showed that 2.2% had cognitive problems lasting 3 months or longer after symptomatic infection. Moreover, data from patients with severe COVID suggested SARS-CoV-2 infection may raise the risk of subsequent neurodegeneration.

"Since the beginning of the SARS-CoV-2 pandemic, the medical community has experienced an influx of patients reporting new cognitive difficulties months after infection clearance," Weisenbach told MedPage Today.

"There is evidence in the research literature of objective cognitive impairment in some individuals following infection; however, many studies have methodological weaknesses that limit the conclusions that can be drawn and applied in clinical settings," she said.

The task force outlined three recommendations based on the group proposed in 2021.

The first calls for a rigorous assessment of post-COVID cognitive dysfunction. Studies relying on self-reported data early in the pandemic have skewed perceptions about the frequency of cognitive dysfunction, Weisenbach and co-authors pointed out, and objective and subjective findings often don't align with each other. Comprehensive test batteries should be used, and studies should include control groups, diverse samples, and when possible, pre-pandemic and post-pandemic data, they argued.

The group's second recommendation was for new research to identify clinical phenotypes. COVID severity, age, family history, and pre-existing cognitive or psychiatric disorders are factors to consider, the task force observed. Other phenotypes may be based on COVID-19 variants, vaccination status, or history of other viral illnesses or pre-existing autoimmune conditions.

Finally, psychosocial factors need to be assessed given the controversies surrounding post-COVID-19 cognitive dysfunction, including skepticism of its existence and disagreement on its cause, Weisenbach and co-authors said.

"This controversy is familiar to neuropsychologists, who frequently evaluate patients with similarly controversial conditions, such as myalgic encephalomyelitis, or chronic fatigue syndrome," the task force said. "Perhaps because psychiatric disorders can co-occur with these multifaceted conditions, many have dismissed these conditions as being psychosomatic with nonbiologic underpinnings."

"This broad dismissal is contrary to scientific evidence and can be harmful for patients and communities affected," the group added. It's possible that in some people, cognitive symptoms may reflect an interplay between illness and psychological and social factors, and in others it's associated with a postviral syndrome and persistent inflammation, they suggested.

Clinical studies will likely have different results than those from large cohorts, Weisenbach and colleagues noted.

"Together, these data will allow improved clarity regarding the pathophysiology of post-COVID-19 cognitive dysfunction and factors that contribute to symptom persistence," they wrote. "Ultimately, this will create opportunities for the development of effective treatment interventions using a personalized medicine approach."

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