Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings

Abstract

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18 FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

Understanding the Post COVID-19 Condition (Long COVID) in Adults and the Expected Burden for Ontario

“…14 A prospective observational cohort study of individuals with polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection and mild COVID-19 presentation examined neurological impairment four months after infection using neuropsychological, ocular, and neurological tests, immune marker assays, structural magnetic resonance imaging (MRI), and 18 FDG-PET neuroimaging. 15 In approximately 25% of individuals, a specific vasoconstrictive deficit (atypical difficulty in using visual and spatial information to guide complex behaviours) was detected, which was associated with changes in molecular and structural brain imaging as well as correlation with upregulation of peripheral immune markers.…”

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders

“…In a study ( de Paula et al., 2022 ) performed with 195 individuals with mild COVID-19, 26% had a visuoconstructive deficiency, a typical early manifestation of Alzheimer’s disease. There was also increased expression of 11 plasma biomarkers, including chemokines and growth factors.…”

“…Most of the volunteers are health professionals who work in the hospital region and learned about the study through advertisements made by the institutions. The mean age of the cohort was 38 years ( de Paula et al., 2022 ).…”

“…A better understanding of anosmia and ageusia may improve our knowledge of long-lasting cognitive disorders, including long-COVID-19. Future studies will investigate the relative expression of key olfactory and sustentacular cell marker genes in samples collected from post-COVID-19 patients (six months to one year after contracting COVID-19) with or without anosmia and/or ageusia, using neuropsychological tests ( de Paula et al., 2022 ).…”

Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management

“…In view of the various clinical manifestations of PC19S on the neurological system, some studies have investigated the effect of biomarkers on the central nervous system, such as myelin oligodendrocyte glycoprotein (MOG) and CCL-11 [ 74 ]. In patients with a neurological presentation of PC19S, reactive microglia with astrocyte reactivity, alteration of hippocampal neurogenesis, myelinated axons and oligodendrocytes have been reported in literature [ 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. In view of this, several mechanisms have been proposed: Cytokine-associated immune dysregulation disrupts myelin hemostasis and plasticity, impairing hippocampal neurogenesis with neurotoxic astrocyte reactivity.…”