COVID-19 survivors show lasting brain function alterations, fMRI study finds

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In a recent study published in The Lancet Regional Health – Western Pacific, a team of researchers from China and the Netherlands used resting-state functional magnetic resonance imaging or rs-fMRI to examine the long-term impact of coronavirus disease 2019 (COVID-19) on brain function, based on reports of persistent neurological, cognitive, and psychiatric symptoms in individuals recovering from the disease.

Study: Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study. Image Credit: Aleksandar Malivuk/Shutterstock.comStudy: Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study. Image Credit: Aleksandar Malivuk/


Although concerted global efforts in medicine have helped contain the spread of the COVID-19 pandemic, there is substantial evidence indicating that a significant portion of individuals recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections experience long coronavirus disease (long COVID) or post COVID syndrome.

The symptoms of long COVID are varied and impact a wide range of organ systems. While the most common symptoms include fatigue, dyspnea, and post-exertional malaise, individuals experiencing post-COVID syndrome also report experiencing cognitive, neurological, and mental health symptoms such as brain fog, anxiety, inability to concentrate, sleep disturbances, and depression.

Studies have confirmed deficits in specific domains of cognition as long-term impacts of SARS-CoV-2 infections.

Research also indicates that individuals who were infected with the original strain of SARS-CoV-2 or the alpha variant and required hospitalization experienced larger cognitive deficits than other COVID-19 patients.

However, the underlying mechanisms or pathophysiology of the neuropsychiatric or cognitive deficits in long COVID patients remain unclear.

About the study

The present study aimed to understand the long-term cognitive, neurological, and psychiatric impact of COVID-19 and the brain alterations in long-term COVID patients two years after SARS-CoV-2 infections using rs-fMRI.

The study included adults between the ages of 18 and 65 and included individuals previously infected with SARS-CoV-2, as well as healthy controls.

Medical records confirming a COVID-19 diagnosis were required to categorize a participant as a COVID-19 survivor, while the healthy controls were defined as individuals with no history or medical records of a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test.

Individuals with a current history of neurological or psychiatric diseases, stroke, or brain injury, pregnant or lactating women, or individuals with metallic or electronic implants, claustrophobia, or any other contraindications for the MRI were excluded.

A wide range of measurements, including demographic characteristics such as age, sex, and education levels, as well as information on comorbidities, smoking behavior, mental disorder history, vaccination status for COVID-19, hospitalization duration, and time between COVID-19 diagnosis and follow-up, were obtained from all participants.

The Cognitive Failures Questionnaire was employed to assess cognitive function, and tasks assessing memory recall were used to evaluate working memory.

Additional questionnaires were used to assess mental and physical health fatigue, depression symptoms, anxiety symptoms, insomnia severity, post-traumatic stress disorder (PTSD) symptoms, as well as self-reported symptoms of headaches, dizziness, and taste and smell disorders. A magnetic resonance scanner provided scans of the brain at various slice thicknesses and angles.


The study found that individuals who experienced mild to moderate and severe to critical acute symptoms during the SARS-CoV-2 infection had significantly higher cognitive complaints of mental fatigue and cognitive failure compared to healthy individuals in the control group.

However, no significant differences were observed in the cognitive complaints between the individuals who had mild to moderate COVID-19 symptoms and those with severe to critical COVID-19 symptoms.

Furthermore, the two COVID-19 survivor groups and the healthy control groups had similar scores in the Montreal Cognitive Assessment questionnaire, as well as the working memory assessment and simple reaction time tasks.

However, the rates of psychiatric symptoms such as depression, insomnia, PTSD, anxiety, and smell and taste disorders were higher in the two COVID-19 survivor groups as compared to the control group.

Additionally, the results from the rs-fMRI showed that among individuals recovering from COVID-19, the amplitude of low-frequency fluctuation values were significantly higher in the right inferior temporal gyrus, left putamen, and right pallidum of the brain and lower in the left superior temporal gyrus and right superior parietal gyrus.

The regional homogeneity values were also lower in the left postcentral gyrus, right precentral gyrus, left calcarine fissure and left superior temporal gyrus of COVID-19 survivors.

Low regional homogeneity values in the left superior temporal gyrus were also correlated with lower scores on the cognitive fatigue questionnaire and higher mental fatigue.


Overall, the findings indicated that long COVID patients continue to experience persistent cognitive symptoms and neurological and psychiatric complaints and exhibit brain alterations even two years after recovering from the SARS-CoV-2 infection.

The study reported brain function changes in various regions of the brain that could be contributing to the persistent and long-term cognitive complaints experienced by long COVID patients.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.


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