A recent study by neurology researchers at the Barcelona Clinic Hospital sheds light on the cognitive impairments experienced by people suffering from the post-acute syndrome of COVID-19. Their findings revealed significant cognitive impairments, especially in attention, executive functions and verbal memory, that last for at least six months. These cognitive impairments are accompanied by symptoms of depression, apathy, anxiety, fatigue and a general deterioration in well-being. The study: Scientific Reports.
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and rapidly became a global pandemic. Although it primarily affects the respiratory system, its effects extend to different body systems, causing a wide range of symptoms, from mild respiratory problems to severe pneumonia and even death.
The early stage of COVID-19 is characterized by acute symptoms such as fever, cough and shortness of breath that can worsen into more severe complications such as acute respiratory distress syndrome, especially in vulnerable populations such as the elderly and those with underlying medical conditions.
Post-acute COVID-19 syndrome, also known as long COVID, refers to symptoms that persist or appear after the initial infection has subsided. Long COVID is usually defined as symptoms that last for more than three months and continue for at least two months without any other apparent cause.
This condition can develop in anyone infected with COVID-19, regardless of the severity of their initial symptoms. Previous studies have highlighted the high incidence of neurological complications during the acute phase of COVID-19, but the long-term cognitive impact of long COVID has not been thoroughly investigated.
“We were interested in cognitive symptoms after COVID-19 infection. Neurological Cognitive Unit“We encountered a large number of patients reporting such problems, which prompted us to investigate in order to provide accurate information to both patients and physicians, including how long these symptoms last and whether they are associated with changes in neuroimaging or fluid biomarkers,” study authors Nuria Guillén, Agnès Pérez Millán and Raquel Sánchez Valle explained in a joint statement.
The study involved 53 participants referred to the Alzheimer’s and Other Cognitive Disorders Unit at the Barcelona Clinic Hospital between March and November 2021. Inclusion criteria were a diagnosis of COVID-19, cognitive symptoms reported by participants or observers, the presence of cognitive symptoms at least 8 weeks after the onset of COVID-19 symptoms, fluency in Spanish, at least 6 years of formal education, and age between 35 and 65 years. Participants with a previous diagnosis of neurological, psychiatric, or medical illness that could affect cognitive performance were excluded.
Participants underwent comprehensive neuropsychological evaluations at baseline, 1 month, 3 months, and 6 months. These evaluations included tests of verbal and visual memory, language, visuospatial abilities, attention, and executive function. In addition, participants completed questionnaires assessing depression, anxiety, apathy, subjective cognitive decline, fatigue, and overall health. Neuroimaging studies using MRI and body fluid biomarker analyses were also performed at baseline and 6 months.
The study found that 75.5% of participants had cognitive impairment, primarily affecting executive function and verbal memory. Of note, only 24.5% of participants had normal cognitive assessments. Participants also reported significant mental health problems, with 19% reporting moderate to severe depression, 57% moderate to severe anxiety, 64% clinically significant apathy, and 35.4% reporting severe fatigue. Quality of life was significantly lower in all domains measured.
Interestingly, at the 6-month follow-up, cognitive test scores remained largely stable, with only verbal memory tests showing significant improvement. The percentage 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 change over time.
Neuroimaging studies revealed a correlation between cognitive impairment and changes in brain structure. Specifically, visual memory scores were positively correlated with total gray matter volume, subcortical gray matter volume, and left cerebral white matter volume. In addition, gray matter volume reductions were observed in the left hippocampus, right hippocampus, and right thalamus. However, no significant longitudinal changes in global or regional brain structure were detected.
Biochemical analysis showed no significant differences in serum levels of neurofilament light chain protein and glial fibrillary acidic protein between PACS patients and controls. However, certain cytokines were significantly different, with some elevated and others decreased in Long COVID patients. Despite these variations, all values were within the normal range and no significant changes were observed over time.
“In our study, we found that the post-acute syndrome of COVID-19 primarily affects memory, attention, and executive function. Elevated levels of anxiety, depression, apathy, fatigue, and reduced quality of life often accompany these cognitive symptoms. However, these are not associated with neuroimaging changes or humoral biomarkers of inflammation and neuronal damage. Notably, we observed a small improvement in cognitive function over the six months, especially memory,” the researchers told PsyPost.
The limitations of this study include the small sample size, especially for cerebrospinal fluid samples, and the lack of cognitive function assessment before COVID-19 infection. In addition, the study did not include healthy controls or COVID-19-infected individuals without cognitive complaints for neuropsychological or neuroimaging analysis. The short follow-up period and monocentric nature of the study also limit the generalizability of the findings.
Future studies should aim to include larger and more diverse samples and longer follow-up periods to better understand the cognitive and mental health impacts of Long COVID. Furthermore, investigating potential mechanisms underlying these symptoms, such as ongoing inflammation and immune dysregulation, may provide valuable insights. Integrating functional neuroimaging studies may also shed light on neural mechanisms contributing to Long COVID symptoms.
the study, “Cognitive profile, neuroimaging and humoral biomarkers in COVID-19 post-acute syndromeThe authors of the paper are Nuria Guillen, Agnès Pérez-Milán, Noyes Fargas, Gemma M. Jedd-Ibáñez, Lorena Rami, Jordi Sarto, Maria A. Boti, Cristina Arnaldos-Pérez, Raquel Ruiz-Garcia, Laura Naranjo, Bárbara Segura, Mircea Barraza, Rosa Sala-Ronch, Albert Riyadh, Sarah M. Gray, Jason K. Johannesen, Madeleine M. Pantoni, Grant A. Rutledge, Ruta Sawant, Yi Wang, Luke S. Watson, Josep Dalmau and Raquel Sánchez-Valle.
