Current concepts in long COVID-19 brain fog and postural orthostatic tachycardia syndrome

Neurologic complications of long COVID-19 syndrome are one of the leading causes of global disability. In particular, post-COVID-19 cognitive dysfunction and dysautonomia in the form of postural orthostatic tachycardia syndrome (POTS) markedly affect patient quality of life and ability to return to work. The underlying pathophysiology of post-COVID-19 neurologic complications is unknown but is likely multifactorial with immune dysregulation and microvascular dysfunction playing central roles. Specific pathogenic factors with supportive evidence to date include cytokine-mediated inflammation, autoantibodies, immune exhaustion, disruption of the renin-angiotensin system, reduced serotonin levels, and microglial activation. The prevalence of post-COVID-19 cognitive dysfunction ranges from 10% to 88% and is affected by viral variant and hospitalization status among other factors, whereas that of long COVID-19 POTS is unknown due to referral bias and varying definitions. Treatment is largely supportive and often incorporates combined modalities. Marginal benefits with cognitive behavioral therapy, hyperbaric oxygen therapy, and supplements have been found for post-COVID-19 brain fog, whereas established POTS therapies aimed at improving venous return and reducing heart rate may reduce symptoms of long COVID-19 POTS. Although significant recovery has been noted for many cases of post-COVID-19 brain fog and POTS, prospective studies have revealed evidence of persistent symptoms and neurologic deficits a year after infection in some patients. Further studies that provide insight into the underlying pathophysiology of long COVID-19 are needed for development of target directed therapy.