Over half of long COVID patients suffer persistent cognitive slowing, new study reveals

By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.Jan 29 2024

In a recent study published in eClinicalMedicine, researchers determine whether the prevalence of substantial cognitive decline could be used as a diagnostic marker of long coronavirus disease 2019 (COVID-19).

Study: Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study. Image Credit: PeopleImages.com - Yuri A / Shutterstock.com

What is long COVID?

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) at the end of 2019, over 770 million individuals throughout the world have been infected, almost seven million of whom have succumbed to the disease.

Between 30-60% of COVID-19 survivors have reported experiencing persistent symptoms for weeks to months after recovering from SARS-CoV-2 infection, a condition that is now commonly referred to as ‘long COVID.’ The World Health Organization (WHO) and United States Centers for Disease Control and Prevention (CDC) have defined long COVID as prior COVID-19 symptoms that persist or re-emerge within three months of infection recovery or the development of new symptoms that last for at least two months.

‘Brain fog,’ a cognitive condition characterized by confusion, forgetfulness, lack of focus, and a general loss of mental clarity, is one of the most common symptoms associated with long COVID. Impairments in sustained attention capabilities, memory, and cognitive flexibility have also been reported with long COVID, with these symptoms often correlating with structural and functional brain changes.

No diagnostic tests are currently available for long COVID, thus leaving diagnosis to be based on self-reported patient evaluations. Furthermore, there remains a crucial need to clearly define and elucidate the risk factors associated with long COVID to support the development of future interventions to prevent and treat the disease.

About the study

In the present study, researchers used a cohort of European participants to determine whether cognitive slowing was strongly associated with long COVID. Importantly, ‘cognitive slowing’ was defined as increased time to process information and respond to it.

Selected participants were divided into three cohorts, including those with self-reported long COVID (cases), the no-COVID group (healthy controls), and those with a history of prior COVID-19 but not long COVID.

The study participants completed two cognitive function tests, including the Simple Reaction Test (SRT), which involves using a spacebar to respond to monitor-presented visual cues and measure reaction time. In contrast, the Number Vigilance Test (NVT) measures sustained, long-term attentiveness by requiring participants to stay focused while being exposed to a long string of numbers with zero as the odd one out. Six questionnaires measuring mood and mental health, fatigue, sleep, trauma, and intelligence quotient (IQ) were also provided to the study participants.

Study findings

A total of 194 individuals were included in the study, 119 of whom were diagnosed with long COVID, 63 of whom had COVID-19 but not long COVID, and 75 healthy controls. As compared to healthy controls with an average reaction time (RT) of 0.34 seconds for the SRT test, long COVID patients responded significantly slower at a mean of 0.49 seconds. After accounting for the effect of age, the mean RT for long COVID patients was significantly longer than age-matched healthy controls.

Compared to 4% of healthy controls, 53.5% of long COVID patients experienced severe cognitive slowing. Likewise, a significantly greater proportion of moderate-to-severely impaired cases were identified in the long COVID group as compared to both COVID-19 survivors without long COVID and healthy controls.  

Long COVID patients with lower SRT test scores reported significantly lower results in their mental health assessments, exhibited less restful sleep, and reported higher depressive tendencies. Similar to SRT results, NVT estimates differed considerably between COVID-19 survivors and long COVID patients, with long COVID patients taking significantly longer to react to targets. Notably, RT on the NVT was strongly associated with the slow RT observed in SRT, even when age and depression status was considered.

During the NVT, long COVID patients were less vigilant to visual stimuli as compared to healthy controls, with the accuracy of their vigilance declining over time. Long COVID patients with normal response speeds reported feeling significantly more tired than other participants with similar RT, thus indicating that these individuals worked harder to sustain their attention on demanding tasks.

No difference was observed in cognitive slowing between long COVID patients who were hospitalized due to COVID-19 as compared to non-hospitalized long COVID patients. Thus, the severity of acute infection with SARS-CoV-2 does not appear to determine the cognitive effects of long COVID. Likewise, the presence of pre-existing psychological or neurological conditions, such as depression, did not impact cognitive symptoms in long COVID patients.

Conclusions

The current study reports significant cognitive slowing in 53% of long COVID patients that does not appear to improve over time. Rather, persistent cognitive slowing in long COVID patients was found to increase the severity of this neurological symptom in these patients.

There remains a lack of information on the mechanisms responsible for the cognitive deficits observed in long COVID patients. Therefore, additional research incorporating comprehensive neuropsychological assessments is needed on a larger and more diverse cohort of patients.