RT journal article
T1 Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome
A1 Díez-Cirarda, María
A1 Yus-Fuertes, Miguel
A1 Sanchez-Sanchez, Rafael
A1 González Rosa, Javier Jesús
A1 Gonzalez-Escamilla, Gabriel
A1 Gil-Martínez, Lidia
A1 Delgado Casas, Cándida Inés
A1 Gil-Moreno, María José
A1 Valles-Salgado, María
A1 Cano Cano, Fátima
A1 Ojeda-Hernandez, Denise
A1 Gomez-Ruiz, Natividad
A1 Oliver-Mas, Silvia
A1 Benito-Martín, María Soledad
A1 Jorquera, Manuela
A1 de la Fuente, Sarah
A1 Polidura, Carmen
A1 Selma-Calvo, Belén
A1 Arrazola, Juan
A1 Matias-Guiu, Jordi
A1 Gomez-Pinedo, Ulises
A2 Psicología
K1 Post-COVID syndrome
K1 Cognition
K1 Hippocampus
K1 Neuroimaging
K1 Blood biomarkers
K1 Histopathology
AB Background: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. Methods: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. Findings: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. Interpretation: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. Funding: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund “A way to make Europe” (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund “A way to make Europe”) (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).
PB Elsevier
SN 2352-3964
YR 2023
FD 2023
LK http://hdl.handle.net/10498/31772
UL http://hdl.handle.net/10498/31772
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026