A recent study by neurology researchers at the Hospital Clínico de Barcelona has shed light on the cognitive impairment suffered by people with acute post-COVID-19 syndrome. Their results reveal significant cognitive deficits, particularly in attention, executive functions and verbal memory, which persist for at least six months. These cognitive impairments are accompanied by depressive symptoms, apathy, anxiety, fatigue and a poor general state of health. The study was published in Scientific reports.
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and quickly became a global pandemic. It primarily affects the respiratory system, but its impact extends to various body systems, causing a wide range of symptoms from mild breathing problems 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 progress to more serious complications such as acute respiratory distress syndrome, particularly in vulnerable populations such as the elderly and those with underlying health conditions.
Post-acute COVID-19 syndrome, also called long COVID, refers to the persistence or onset of symptoms well after the initial infection has resolved. Typically, long COVID is identified when symptoms persist for more than three months and last for at least two months without another obvious cause.
This pathology can affect anyone who has had COVID-19, regardless of the severity of the 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 poorly studied.
“We were interested in cognitive symptoms after COVID-19 infection because, working in a cognitive unit of a neurology department, we encountered many patients who reported such problems. This prompted us to investigate this topic to provide accurate information to patients and physicians, including the duration of these symptoms and their possible association with changes in neuroimaging or fluid biomarkers,” study authors Núria Guillén, Agnès Pérez-Millan, and Raquel Sánchez-Valle explained in a joint statement.
The study included 53 participants who were referred to the Alzheimer’s Disease and Other Cognitive Disorders Unit at the Hospital Clínica de Barcelona between March and November 2021. Inclusion criteria were a diagnosis of COVID-19, cognitive symptoms reported by the participant or an observer, the 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 an age between 35 and 65 years. Participants with a previous diagnosis of neurological, psychiatric, or medical disorders that could affect cognitive performance were excluded.
Participants underwent comprehensive neuropsychological assessments at baseline, one month, three months, and six months. These assessments included tests of verbal and visual memory, language, visuospatial abilities, attention, and executive functions. In addition, they completed questionnaires assessing depression, anxiety, apathy, subjective cognitive decline, fatigue, and general health. Neuroimaging studies using MRI and fluid biomarker analyses were also conducted at baseline and six months.
The study found that 75.5% of participants had cognitive impairment, primarily affecting executive function and verbal memory. Notably, only 24.5% of participants had normal cognitive assessments. Participants also reported significant mental health problems, with 19% having moderate to severe depression, 57% having moderate to severe anxiety, 64% having clinically significant apathy, and 35.4% having severe fatigue. Quality of life was particularly low across all domains measured.
Interestingly, at the six-month follow-up, cognitive test scores remained broadly stable, with only the verbal memory test showing significant improvement. The proportion of participants with normal cognitive assessments 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 have revealed correlations between cognitive impairment 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. In addition, 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 light neurofilaments and glial fibrillary acidic proteins between PACS patients and controls. However, some cytokines differed significantly, with some being elevated and others reduced in patients with long-duration COVID. Despite these variations, all values were within normal limits and no significant changes were observed over time.
“Our study found that acute post-COVID-19 syndrome primarily affects memory, attention, and executive functions. High levels of anxiety, depression, apathy, fatigue, and 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 modest improvement in cognitive function, particularly memory, over six months,” the researchers told PsyPost.
Limitations of the study include the small sample size, particularly for cerebrospinal fluid samples, and the lack of cognitive assessment prior to COVID-19 infection. Additionally, the study did not include healthy controls or COVID-19-infected participants without cognitive complaints for neuropsychological or neuroimaging analyses. The short follow-up duration and single-center nature of the study also limit the generalizability of the results.
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 potential mechanisms underlying these symptoms, such as ongoing inflammation or immune dysregulation, could provide valuable insights. Integrating functional neuroimaging studies could also help uncover 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.