A recent study by neurology researchers at the Hospital Clínic de Barcelona has shed light on the cognitive impairments experienced by individuals suffering from post-acute COVID-19 syndrome. Their findings reveal significant cognitive deficits, particularly in attention, executive function, and verbal memory, persisting for at least six months. These cognitive impairments are accompanied by depressive symptoms, apathy, anxiety, fatigue, and a generally low health status. The research was published in Scientific Reports.
COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and swiftly led to a global pandemic. It primarily affects the respiratory system, but its impact extends to various bodily systems, causing a wide range of symptoms from mild respiratory issues to severe pneumonia and even death.
The initial phase of COVID-19 is characterized by acute symptoms such as fever, cough, and shortness of breath, which can escalate to more severe complications like acute respiratory distress syndrome, particularly in vulnerable populations such as the elderly and those with underlying health conditions.
Post-acute COVID-19 syndrome, also known as long COVID, refers to the persistence or emergence of symptoms well after the initial infection has resolved. Typically, long COVID is identified when symptoms continue for more than three months and last for at least two months with no other clear cause.
This condition can affect anyone who has had COVID-19, regardless of the severity of their initial illness. Previous studies have highlighted the prevalence of neurological complications during the acute phase of COVID-19, but the long-term cognitive repercussions of long COVID remain underexplored.
“We were interested in cognitive symptoms following COVID-19 infection because, working in a cognitive unit of a neurology department, we encountered numerous patients reporting such issues. This prompted us to investigate it to provide accurate information to both patients and doctors, including the duration of these symptoms and whether they were associated with changes in neuroimaging or fluid biomarkers,” explained study authors Núria Guillén, Agnès Pérez-Millan, and Raquel Sánchez-Valle in a joint statement.
The study involved 53 participants who were referred to the Alzheimer’s Disease and other Cognitive Disorders Unit at the Hospital Clínic de Barcelona between March and November 2021. The inclusion criteria were a COVID-19 diagnosis, cognitive symptoms reported by the participant or an observer, presence of cognitive symptoms for at least eight weeks after the onset of COVID-19 symptoms, fluency in Spanish, at least six years of formal education, and age between 35 and 65 years. Participants with previous diagnoses of neurological, psychiatric, or medical conditions that could affect cognitive performance were excluded.
Participants underwent comprehensive neuropsychological evaluations at baseline, one month, three months, and six months. These evaluations included tests for verbal and visual memory, language, visuospatial abilities, attention, and executive functions. Additionally, they completed questionnaires assessing depression, anxiety, apathy, subjective cognitive decline, fatigue, and overall health status. Neuroimaging studies using MRI and fluid biomarker analyses were also conducted at baseline and six months.
The study found that 75.5% of participants exhibited cognitive impairments, primarily affecting executive functions and verbal memory. Notably, only 24.5% of participants had normal cognitive evaluations. Participants also reported significant mental health issues, with 19% exhibiting moderate to severe depression, 57% experiencing moderate to severe anxiety, 64% showing clinically significant apathy, and 35.4% suffering from severe fatigue. The quality of life was notably low across all measured domains.
Interestingly, at the six-month follow-up, cognitive test scores generally remained stable, with only the verbal memory test showing significant improvement. The proportion of participants with normal cognitive evaluations increased from 24% at baseline to 50% at follow-up. Despite these improvements, mental health symptoms such as anxiety, apathy, and fatigue did not show significant changes over time.
Neuroimaging studies revealed correlations between cognitive impairments and brain structure changes. Specifically, visual memory scores were positively correlated with total gray matter volume, subcortical gray matter volume, and left cerebral white matter volume. Additionally, reductions in gray matter volume were observed in the left hippocampus, right hippocampus, and right thalamus. However, no significant longitudinal changes in global or regional brain structures were detected.
Biochemical analyses showed no significant differences in serum levels of neurofilament-light and glial fibrillary acidic protein between PACS patients and controls. However, certain cytokines differed significantly, with some elevated and others reduced in long COVID patients. Despite these variations, all values were within normal limits, and no significant changes were observed over time.
“Our study found that post-acute COVID-19 syndrome primarily affects memory, attention, and executive function. Elevated levels of anxiety, depression, apathy, fatigue, and a lower perceived quality of life often accompany these cognitive symptoms. However, they are not associated with changes in neuroimaging or fluid biomarkers of inflammation or neuronal damage. Notably, we observed a slight improvement in cognitive function, particularly in memory, over six months,” the researchers told PsyPost.
The study’s limitations include a small sample size, particularly for cerebrospinal fluid samples, and the absence of cognitive assessments before COVID-19 infection. Additionally, the study did not include healthy controls or participants with COVID-19 infection without cognitive complaints for neuropsychological or neuroimaging analyses. The short follow-up duration and the unicentric nature of the study also limit the generalizability of the findings.
Future research should aim to include larger, more diverse samples and longer follow-up periods to better understand the cognitive and mental health impacts of long COVID. Additionally, exploring the potential mechanisms underlying these symptoms, such as ongoing inflammation or immune dysregulation, could provide valuable insights. Integrating functional neuroimaging studies could also help uncover the neural mechanisms contributing to long COVID symptoms.
The study, “Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome,” was authored by Núria Guillén, Agnès Pérez-Millan, Neus Falgàs, Gema M. Lledó-Ibáñez, Lorena Rami, Jordi Sarto, Maria A. Botí, Cristina Arnaldos-Pérez, Raquel Ruiz-García, Laura Naranjo, Bàrbara Segura, Mircea Balasa, Roser Sala-Llonch, Albert Lladó, Sarah M. Gray, Jason K. Johannesen, Madeline M. Pantoni, Grant A. Rutledge, Ruta Sawant, Yi Wang, Luke S. Watson, Josep Dalmau, and Raquel Sanchez-Valle.
