Clearing the ‘Brain Fog’ in Long COVID


Experts address cognitive dysfunction found in patients with long COVID at the 2022 APA Annual Meeting.




How can we “clear the fog” surrounding brain fog? Experts addressed the cognitive dysfunction, or “brain fog,” observed in patients with long COVID—as well as those with fibromyalgia, with chronic fatigue syndrome, and undergoing chemotherapy treatment—at the 2022 American Psychiatric Association (APA) Annual Meeting.

Maria Tiamson-Kassab, MD, of the Moores Cancer Center at UC San Diego introduced the presidential session, which was delivered on behalf of the Academy of Consultation-Liaison Psychiatry. Durga Roy, MD, FACLP, of Johns Hopkins Bayview Neuropsychiatry Clinic and Johns Hopkins University School of Medicine discussed symptoms and pathophysiology of brain fog in long COVID, plus some ways clinicians can manage patients with brain fog after long COVID. Additional speakers included Jon Levenson, MD, of Columbia University Irving Medical Center and Susan Abbey, MD, FRCPC, of the University of Toronto.

Tiamson-Kassab explained that “brain fog” is a nonmedical term used to describe what patients feel in any condition that causes confusion, memory loss, inability to concentrate or focus, and difficulty with word-finding or multitasking. It is found in many conditions, including long COVID, fibromyalgia, chronic fatigue syndrome, pregnancy, multiple sclerosis, and systemic lupus erythematosus, as well as in cancer treatments and certain medications. Neurocognitive domains affected in brain fog include planning; decision-making; processing speed; complex, divided, and selective sustained attention; free and cued recall; and working, procedural, and autobiographical memory.

Cognitive dysfunction is a particular concern in long COVID, as many patients have reported symptoms such as brain fog weeks or months after SARS-CoV-2 infection, Roy explained. Current definitions of long COVID differ. The National institute for Health and Care Excellence defines it as a constellation of symptoms that develop during or following SARS-CoV-2 infection persisting for 12 weeks or more; the World Health Organization defines it as persistent symptoms occurring 3 months from onset in individuals with past confirmed or probable SARS-CoV-2 infection and persisting for at least 2 months; and the Centers for Disease Control and Prevention defines it as a range of symptoms that can last weeks or months after initial SARS-CoV-2 infection, which can appear weeks after infection. In all cases, the symptoms cannot be sufficiently explained by any alternative diagnosis, and they can present even if the initial SARS-CoV-2 infection was mild or asymptomatic.

Although a range of symptoms may present, “fatigue and cognitive impairment appear to be the most debilitating symptoms of long COVID,” Roy said. The exact cause of brain fog and other symptoms in long COVID is not yet clear, however: “We have to be cognizant of the fact that, potentially, anxiety and depression could be factors that are driving the fatigue and cognitive impairment,” Roy said. “And pathophysiology can stem from numerous hypotheses, neuroinflammation, or neurotropism, but the idea is that the frontal limbic pathway seems to consistently be something that we’re hearing about when it comes to cognitive problems in long COVID.”

In terms of treatment, Roy recommended both pharmacologic and nonpharmacologic interventions targeting mental fatigue and cognition. Pharmacologic interventions may include medications such as methylphenidate, donepezil, modafinil, luteolin, nicotinamide riboside, vitamin C or probiotic supplementation, monoclonal antibodies, or adaptogens. Suggested nonpharmacologic interventions include cognitive behavioral therapy, graded exercise therapy, pacing, and rehabilitation.

With studies on brain fog in long COVID still new and in development, however, Roy emphasized a need for more research to improve treatment and patient quality of life. “This is definitely a syndrome that we don’t know very much about,” Roy said. “It’s something that we really need to study more in order to get a better grasp on what’s going on.”

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