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

The Coronavirus Disease 2019 (COVID-19) has affected all aspects of life around the world. Neuroimaging evidence suggests the novel coronavirus can attack the central nervous system (CNS), causing cerebro-vascular abnormalities in the brain. This can lead to focal changes in cerebral blood flow and metabolic oxygen consumption rate in the brain. However, the extent and spatial locations of brain alterations in COVID-19 survivors are largely unknown. In this study, we have assessed brain functional connectivity (FC) using resting-state functional MRI (RS-fMRI) in 38 (25 males) COVID patients two weeks after hospital discharge, when PCR negative and 31 (24 males) healthy subjects. FC was estimated using independent component analysis (ICA) and dual regression. When compared to the healthy group, the COVID group demonstrated significantly enhanced FC in the basal ganglia and precuneus networks (family wise error (fwe) corrected, pfwe < 0.05), while, on the other hand, reduced FC in the language network (pfwe < 0.05). The COVID group also experienced higher fatigue levels during work, compared to the healthy group (p < 0.001). Moreover, within the precuneus network, we noticed a significant negative correlation between FC and fatigue scores across groups (Spearmans {rho} = - 0.47, p = 0.001, r2 = 0.22). Interestingly, this relationship was found to be significantly stronger among COVID survivors within the left parietal lobe, which is known to be structurally and functionally associated with fatigue in other neurological disorders. Significance StatementEarly neuroimaging studies have mostly focused on structural MRI imaging to report brain abnormalities in acutely ill COVID-19 patients. It is not clear whether functional abnormalities co-exist with structural alterations in patients who have survived the infection and have been discharged from the hospital. A few recent studies have emerged which attempted to address the structural/functional alterations. However, further investigations across different sites are necessary for more conclusive inference. More importantly, fatigue is a highly prevalent symptom among COVID survivors, therefore, the relations of brain imaging abnormalities to fatigue should be investigated. In this study, we try to address these gaps, by collecting imaging data from COVID survivors, now PCR negative, and healthy subjects from a single site - the Indian Institute of Technology (IIT), Delhi, India. Furthermore, this is a continuation of an ongoing study. We have recently shown structural abnormalities and stronger gray matter volume (GMV) correlates of self-reported fatigue in this group of COVID survivors compared to healthy subjects (Hafiz et al., 2022).