Cognitive Impairment in Long COVID

COVID-19 has been in our news feed for over 2 years. From new variants to rising cases and public health measures, COVID has been all the rage. However, a new phenomenon that's crept into our feeds this past year is long COVID.

Long COVID has been variably defined by several organizations such as the Centers for Disease Control & Prevention, the National Institute for Health and Care Excellence, as well as the National Institutes of Health. According to the World Health Organization, long COVID, (otherwise known as post-COVID condition) is defined as the new onset and/or persistence of symptoms related to an acute SARS-CoV-2 infection that occurs 3 months postinfection and lasts for at least 2 months. Symptoms of post-COVID condition include fatigue, cognitive impairment, headache, shortness of breath, and trouble sleeping, among others.

An increasing number of individuals with long COVID have requested disability leave owing to the enduring and debilitating symptoms of this medical phenomenon. A recent meta-analysis investigating the proportion of cognitive impairment and fatigue among individuals with long COVID found that approximately one fifth and one third experience persistent cognitive impairment and fatigue, respectively. These symptoms are reported to create a significant burden on function and quality of life, and there is currently no approved nor established treatment.

Multiple mechanisms have been put forth to explain this phenomenon. Hyperinflammation has been commonly discussed as a driving force behind cognitive impairment and long COVID (eg, neuroinflammation). The causal relationship between inflammation and cognitive impairment is well established.

However, it may also be a confluence of systemic sequelae (eg, hyperinflammation, latent viral reactivity, autonomic nervous system dysfunction) that engender this persistent phenomenon. Lingering symptoms from a viral infection are not previously unheard of. For example, following the 1918 Spanish influenza pandemic, there was an encephalitis lethargica (von Economo's encephalitis) epidemic from 1917 to 1928, which was hypothesized to be a result of the influenza virus.

Part of my research as a master's student has been to evaluate the effectiveness of a procognitive antidepressant called vortioxetine in treating cognitive impairment in long COVID. When I read about cognitive impairment in long COVID, I feel far removed. However, when I speak to potential participants or those currently enrolled, it's quite astonishing to see how significantly COVID-19 and long COVID have affected individuals who were previously fully functional in terms of memory, speech, and concentration, to name a few.

It's not uncommon for these individuals to go on disability or retire early because of the severity of their symptoms. Hence, the impetus for investigating psychotropic medications are related to its anti-inflammatory effects (eg, reducing cytokine levels). However, all this is to say is that we should also be looking out for potential influence of preexisting medical and physical comorbidities, as well as socioeconomic determinants of health, which may pose as risk factors for long COVID.

Put simply, when characterizing this pandemic, it should not only be interpreted as a pandemic of an acute infection but also one that includes long-term consequences — from long COVID to its burdensome effects on the healthcare system.

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About Leanna Lui

Leanna M.W. Lui, HBSc, completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc candidate. Her interests include mood disorders, health economics, public health, and applications of artificial intelligence. In her spare time, she is a fencer with the University of Toronto Varsity Fencing team and the Canadian Fencing Federation.

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