Higher Limbic and Basal Ganglia volumes in surviving COVID-negative patients and the relations to fatigue

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Among several systemic abnormalities, little is known about the critical attack on the central nervous system (CNS). Several patient reports with multiple pathologies – ischemic strokes, mild infarcts, encephalitis, cerebro-vascular abnormalities, cerebral inflammation, and loss of consciousness, indicate CNS involvement. However, due to limited neuroimaging studies, conclusive group level effects are scarce in the literature and replication studies are necessary to verify if these effects persist in surviving acute-COVID patients. Furthermore, recent reports indicate fatigue is highly prevalent among slowly recovering patients. How early structural changes relate to fatigue need to be investigated. Our goal was to address this by scanning COVID subjects two weeks after hospital discharge. We hypothesized these surviving patients will demonstrate altered gray matter volume (GMV) when compared to healthy controls and further demonstrate correlation of GMV with fatigue. Voxel-based morphometry was applied to T1-weighted MRI images between 46 patients with COVID and 32 healthy controls. Significantly higher GMV in the Limbic System and Basal Ganglia regions were observed in surviving COVID-19 patients when compared to healthy controls. Moreover, within the patient group, there was a significant positive correlation between GMV and self-reported fatigue scores during work, within the ventral Basal Ganglia and Ventromedial Prefrontal Cortex regions. Therefore, our results align with both single case acute patient reports and current group level neuroimaging findings. Finally, we newly report a positive correlation of GMV with fatigue in COVID survivors.

Assessing functional connectivity differences and work-related fatigue in surviving COVID-negative patients

“…Despite fatigue being one of the most frequently reported symptoms, very little is known of functional brain correlates of fatigue within survivors. Prior to the current study, we have shown a positive correlation of gray matter volume within regions from the ventral basal ganglia (BG) and ventromedial prefrontal cortex (vmPFC) with self-reported fatigue at work in survivors two weeks after hospital discharge (Hafiz et al, 2021) (in press). Here, we continue our investigation to explore the functional correlates of fatigue among the same set of survivors.…”

“…This is a continuation of our recent publication using the same sample groups where structural brain alterations were reported (Hafiz et al, 2021). 47 COVID patients and 35 healthy controls were recruited from a single site located at Indian Institute of Technology (IIT), Delhi, India.…”

“…This led to a rise in follow-up studies on a span of 3 to 6 months after initial infection (Lu et al, 2020; Tu et al, 2021) and longitudinal designs (Douaud et al, 2021) where structural abnormalities were investigated before and after the pandemic. We have recently shown gray matter volume differences in survivors after a shorter interval (2 weeks after hospital discharge), as well as, a relation between gray matter volume and self-reported fatigue at work (Hafiz et al, 2021) (in press). It is still unclear, though, if such structural abnormalities are also accompanied by functional brain alterations in COVID-19 survivors.…”

Decreased cerebral blood flow in non-hospitalized adults who self-isolated due to COVID-19

“…We hypothesized that the adults who previously self-isolated due to COVID-19 would exhibit altered CBF relative to controls, when assessed weeks/months beyond infection. Given the prevalence of fatigue as a symptom of the post-COVID-19 condition, 7,8,[32][33][34][35] we then performed an exploratory analysis of the association between self-reported fatigue and CBF among COVID-19 participants.…”

“…There have been efforts to characterize COVID-19 based on symptoms, with the hope of predicting severity and likelihood of the post-COVID-19 condition. 32,33 Others have observed fatigue-related differences in brain structure and function in those recovering from COVID-19, 35 such as functional connectivity alterations in parietal regions. 34 Interestingly, the post-COVID-19 condition shares many common features with chronic fatigue syndrome (i.e., myalgic encephalomyelitis), a disorder that can be triggered by viral infection, 63 and that is characterized by decreased CBF, such as within the lingual gyrus.…”