Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals

Churchill, Nathan W.; Roudaia, Eugenie; Chen, J. Jean; Gilboa, Asaf; Sekuler, Allison B.; Ji, Xiang; Gao, Fuqiang; Lin, Zhongmin; Jegatheesan, Aravinthan; Masellis, Mario; Goubran, Maged; Rabin, Jennifer S.; Lam, Benjamin; Cheng, Ivy; Fowler, Robert; Heyn, Chris; Black, Sandra E.; MacIntosh, Bradley J.; Graham, Simon J.; Schweizer, Tom A.

doi:10.3389/fneur.2023.1136408

Cited by 22 publications

(6 citation statements)

References 50 publications

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“…In terms of the psychological burden, results are also consistent with the similar levels of symptom burden seen in this study's COVID‐19 and control groups as examined in Churchill et al. ( 2023 ). However, these findings may be due to the relatively mild sequelae in the current sample of non‐hospitalized individuals with COVID‐19, compared to others who may experience flagrant PACS.…”

Section: Discussionsupporting

confidence: 90%

“…This suggests that, contrary to study hypotheses, PACS alone does not substantially alter functional brain dynamics relative to symptomatic non-COVID infection, despite evidence of COVID-19 targeting brain tissues (Baig et al, 2020;Galea et al, 2022). In terms of the psychological burden, results are also consistent with the similar levels of symptom burden seen in this study's COVID-19 and control groups as examined in Churchill et al (2023). However, these findings may be due to the relatively mild sequelae in the current sample of non-hospitalized individuals with COVID-19, compared to others who may experience flagrant PACS.…”

Section: Discussionsupporting

confidence: 64%

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Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals

Churchill,

Roudaia,

Jean Chen

et al. 2023

Brain and Behavior

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IntroductionPost‐acute coronavirus disease 2019 (COVID‐19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long‐term effects of COVID‐19 and post‐COVID headache on brain function remain poorly understood, particularly among non‐hospitalized individuals. This study focused on the power‐law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post‐COVID syndrome, with greatest reductions among those with persistent headache.MethodsResting‐state blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID‐19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu‐like symptoms but tested negative for COVID‐19. Individuals were assessed an average of 4–5 months after COVID testing, in a cross‐sectional, observational study design.ResultsNo significant differences in H values were found between non‐headache COVID‐19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non‐headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity.ConclusionsThese findings provide new insights into the neurophysiological mechanisms that underlie persistent post‐COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 64%

Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals

Churchill,

Roudaia,

Jean Chen

et al. 2023

Brain and Behavior

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“…Other associated factors (e.g., post-traumatic stress disorder, medical comorbidities, reinfections, and increasing age) may also be related to the development of "delayed" post-COVID cognitive symptoms. Post-COVID cognitive symptoms may arise from a combination of biological factors, e.g., persistent viral damage, neuroinflammation, damage to the blood-brain barrier, neural network dysfunction, or altered excitability and neurotransmission in the primary motor cortex (Ortelli et al, 2002;Burks et al, 2021;Churchill et al, 2023), as well as psychological factors, e.g., anxiety, depression, or posttraumatic stress disorder (PTSD) . Considering the long regeneration time of nervous system neurons, the recovery of post-COVID cognitive symptoms could be longer than expected.…”

Section: Discussionmentioning

confidence: 99%

Trajectory of post-COVID brain fog, memory loss, and concentration loss in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study

Fernández-de-las-Peñas,

Cancela-Cilleruelo,

Rodríguez-Jiménez

et al. 2023

Front. Hum. Neurosci.

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ObjectiveThis study aimed to apply Sankey plots and exponential bar plots for visualizing the trajectory of post-COVID brain fog, memory loss, and concentration loss in a cohort of previously hospitalized COVID-19 survivors.MethodsA sample of 1,266 previously hospitalized patients due to COVID-19 during the first wave of the pandemic were assessed at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of the following self-reported cognitive symptoms: brain fog (defined as self-perception of sluggish or fuzzy thinking), memory loss (defined as self-perception of unusual forgetfulness), and concentration loss (defined as self-perception of not being able to maintain attention). We asked about symptoms that individuals had not experienced previously, and they attributed them to the acute infection. Clinical and hospitalization data were collected from hospital medical records.ResultsThe Sankey plots revealed that the prevalence of post-COVID brain fog was 8.37% (n = 106) at T1, 4.7% (n = 60) at T2, and 5.1% (n = 65) at T3, whereas the prevalence of post-COVID memory loss was 14.9% (n = 189) at T1, 11.4% (n = 145) at T2, and 12.12% (n = 154) at T3. Finally, the prevalence of post-COVID concentration loss decreased from 6.86% (n = 87) at T1, to 4.78% (n = 60) at T2, and to 2.63% (n = 33) at T3. The recovery exponential curves show a decreasing trend, indicating that these post-COVID cognitive symptoms recovered in the following years after discharge. The regression models did not reveal any medical record data associated with post-COVID brain fog, memory loss, or concentration loss in the long term.ConclusionThe use of Sankey plots shows a fluctuating evolution of post-COVID brain fog, memory loss, or concentration loss during the first years after the infection. In addition, exponential bar plots revealed a decrease in the prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.

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“…It was reported that one patient who had sensorineural hearing loss of the left ear as a consequence of COVID-19 showed hypometabolism of the left temporal region on 18 F-FDG PET/CT scans and anomalies in rsf-MRI in the same region (29). Another study using rsf-MRI, led by Churchill et al (30), demonstrated that patients who are currently experiencing a larger number of Neuro-PASC symptoms tended to have altered connectivity between parietal, temporal, occipital and subcortical regions using BOLD rsf-MRI. Additionally, distinct patterns correlated to the intensity of PASC symptoms.…”

Section: Functional Mrimentioning

confidence: 99%

“…Additionally, distinct patterns correlated to the intensity of PASC symptoms. They elude to the fact that this could be a useful tool to differentiate between Neuro-PASC and other non-COVID-related infections (30).…”

Section: Functional Mrimentioning

confidence: 99%

Radiological markers of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection: a mini-review

Cull,

Al Qadi,

Stadler

et al. 2023

Front. Neurol.

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The neurological impact of COVID-19 is a rising concern among medical professionals, as patients continue to experience symptoms long after their recovery. This condition, known as neurological post-acute sequelae of COVID-19 (Neuro-PASC), can last for more than 12 weeks and includes symptoms such as attention disorders, brain fog, fatigue, and memory loss. However, researchers and health professionals face significant challenges in understanding how COVID-19 affects the brain, limiting the development of effective prevention and treatment strategies. In this mini-review, we provide readers with up-to-date information on the imaging techniques currently available for measuring the neurological impact of post-SARS-CoV-2 infection. Our search of PubMed and Google Scholar databases yielded 38 articles on various brain imaging techniques, including structural MRI (magnetic resonance imaging), functional MRI, diffusion MRI, susceptibility-weighted imaging, SPECT (single-photon emission computed tomography) imaging, and PET (positron emission tomography) imaging. We also discuss the optimal usage, limitations, and potential benefits of these techniques. Our findings show that various cerebral imaging techniques have been evaluated to identify a reliable marker for Neuro-PASC. For instance, 18F-FDG-PET/CT and functional MRI have demonstrated hypometabolism in cerebral regions that are directly linked to patient symptoms. Structural MRI studies have revealed different findings, such as infarcts, white matter atrophy, and changes in gray matter volumes. One SPECT imaging study noted frontal lobe hypometabolism, while diffusion MRI showed increased diffusivity in the limbic and olfactory cortical systems. The sequence SWI showed abnormalities primarily in white matter near the gray-white matter junction. A study on 18F-amyloid PET/CT found amyloid lesions in frontal and anterior cingulate cortex areas, and a study on arterial spin labeling (ASL) found hypoperfusion primarily in the frontal lobe. While accessibility and cost limit the widespread use of 18F-FDG-PET/CT scans and functional MRI, they seem to be the most promising techniques. SPECT, SWI sequence, and 18F-amyloid PET/CT require further investigation. Nevertheless, imaging remains a reliable tool for diagnosing Neuro-PASC and monitoring recovery.

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Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals

Cited by 22 publications

References 50 publications

Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals

Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals

Trajectory of post-COVID brain fog, memory loss, and concentration loss in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study

Radiological markers of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection: a mini-review

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