Have there been any studies around the treatment of "COVID fog?" Any information regarding nutritional support or medications that help patients recover from post-COVID-19 brain fog?

Comment by InpharmD Researcher

Unfortunately, there are no clinically effective interventions for long COVID-19 syndrome associated brain fog. There are limited studies of the condition. Current recommendations from editorials, commentaries, and case reports focus on mast cell inhibition and suggest hypothetical benefit with flavonoids (particularly luteolin), certain antihistamines (particularly rupatadine), and nonpharmacological approaches such as enhanced external counterpulsation (EECP). Patients may also benefit from avoiding alcohol and discontinuing any contributing medications.

PubMed: treatment COVID-19 brain fog= 16 results (3 relevant)

Background

Unfortunately, there are no clinically effective interventions for long COVID-19 syndrome associated brain fog. It is difficult to balance stimulating or suppressing the immune system, as antibody production and T cells appear to be protective, while pro‐inflammatory cytokines are destructive. Authors of one commentary suggest a reasonable approach especially for brain fog associated with long‐COVID would be inhibition of mast cell‐associated neuroinflammation. The authors identify mast cells could be potentially be inhibited with the structurally related natural flavonoids luteolin and quercetin. Both are readily available and are generally considered safe. Luteolin better penetrates into the brain, inhibits both microglia and mast cells and has been reported to reduce neuroinflammation and cognitive dysfunction, including Alzheimer's disease in humans and animal models. Both luteolin and quercetin are difficult to absorb after oral administration, but their pharmacokinetics are greatly improved in liposomal preparations using olive pomace oil. However, clinicians should appreciate that luteolin is present in numerous dietary supplements and has wide variations in source, content, and purity. [1]

An editorial on COVID-19 and multisystem inflammatory syndrome lists brain fog as one of the symptoms of the syndrome. Regarding treatment possibilities, the authors suggest the flavonoid luteolin preferably with a liposomal formulation due to poor absorption (e.g. PureLut or FibroProtek). They also recommend a specific antihistamine, rupatadine, as it also has anti-platelet activating factor activity and inhibits mast cells which have been associated with COVID-19 cytokine storms. The dose, duration, and timing after COVID-19 infection of these potential pharmacotherapies were not discussed. [2]

According to a news release from the University of Alabama at Birmingham (UAB), there are no current treatments for brain fog attributed to COVID-19, but a new clinical trial at UAB is testing a proven rehabilitation method known as Constraint-Induced Therapy (CI Therapy), which is used internationally to help patients regain limb function and language abilities following a stroke. It can also be used to treat patients with traumatic brain injury, multiple sclerosis and cerebral palsy or brain damage in pediatric patients. A pilot study funded by UAB aims to recruit at least 20 adult patients aged 18 or older who have recovered from COVID-19, but are experiencing memory loss, brain fog or other cognitive issues. Patients will receive 35 hours of CI Cognitive Therapy in a clinic, which includes computer-based speed-of-processing training and a component called shaping, which involves training simulated cognitive activities in the clinic that are made progressively harder over time. [3]

A recent Harvard Health blog emphasized the importance of seeking primary care providers regarding lingering symptoms post-COVID-19 infections, including brain fog and other neurologic symptoms (e.g., weakness, numbness, tingling, loss of smell or taste). The authors recommended a couple of non-pharmacological interventions that might be helpful in clearing the brain fog while promoting cognitive functions such as performing aerobic exercise, avoiding alcohol and contributing medications, and pursuing other beneficial activities. [4]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Have there been any studies around treatment of "COVID fog?" Any information regarding nutritional support or medications that help patients recover from post COVID-19 brain fog?

Level of evidence

D - Case reports or unreliable data Read more→

Please see Table 1 for your response.

Enhanced External Counterpulsation as a Novel Treatment for Post-acute COVID-19 Sequelae
Design	Case report; N= 1
Case presentation	In October 2020, a 38-year-old Hispanic woman with no preexisting health conditions noted the onset of what she was certain to be her usual allergy symptoms, including itchy eyes, sneezing, sinus drainage, and headache. She was tested for both influenza A/B and COVID-19 via antigen test, with a negative flu result but a positive COVID-19 result. For verification, she also took a COVID-19 polymerase chain reaction test that also resulted in a positive for infection. She was prescribed conventional therapy at the time, including a cocktail of three vitamins (vitamin D-3 2,000 IU daily, zinc 50 mg daily, and vitamin C 500 mg daily), hydroxychloroquine 200 mg twice daily for six days, and Tylenol 500 mg two tablets every four to six hours as needed. She had an at-home recovery and reported her predominant symptoms during the acute phase as fatigue, headaches, body pain, and shortness of breath. After most of her symptoms were resolved, she continued to have periodic episodes of fatigue and headaches, along with random shortness of breath while at rest and during activities for months beyond the acute phase of the illness. She also noted the presence of “brain fog,” as if lacking the same clarity that she had prior to her illness. These symptoms persisted for three months before the patient underwent enhanced external counterpulsation (EECP) therapy for one-hour sessions, three times per week. The patient underwent a non-standard EECP regimen of three days per week for five weeks due to convenience. This therapy was chosen based on EECP’s unique mechanism of action and the known cardiac and extra-cardiac effects. After one week, her “brain fog” had improved, with shortness of breath improving after 1.5 weeks. The patient reported returning to pre-COVID-19 health and fitness after approximately five weeks of EECP treatment.
Study Author Conclusions	To our knowledge, this is the first case of using EECP for post-COVID dyspnea, fatigue, and “brain fog.” There are no current guidelines for the treatment of PASC, and management of the condition is largely based on patient presentation and symptoms and requires the efforts of a multidisciplinary team. This initial case report of a patient recovering from her post-acute COVID-19 symptoms suggests EECP may serve as a novel treatment modality for the management of PASC. More data are needed to further validate these findings.

References:

Dayrit JK, Verduzco-Gutierrez M, Teal A, Shah SA. Enhanced External Counterpulsation as a Novel Treatment for Post-acute COVID-19 Sequelae. Cureus. 2021;13(4):e14358. Published 2021 Apr 7. doi:10.7759/cureus.14358