Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for covid-19 in Brazil

Felipe Kenji Sudo; Talita P Pinto; Fernanda G Q Barros-Aragao; Ivanei Bramati; Theo F Marins; Marina Monteiro; Fernanda Meireles; Rejane Soares; Pilar Erthal; Victor Calil; Naima Assuncao; Natalia Oliveira; Joana Bondarovsky; Camila Lima; Beatriz Chagas; Alana Batista; Julia Lins; Felippe Mendonca; Andrea Silveira de Souza; Fernanda C Rodrigues; Gabriel R de Freitas; Pedro Kurtz; Paulo Mattos; Erika C Rodrigues; Fernanda G De Felice; Fernanda Tovar-Moll

doi:10.1016/j.bbi.2023.10.020

Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for covid-19 in Brazil

Brain Behav Immun. 2023 Oct 28:S0889-1591(23)00318-5. doi: 10.1016/j.bbi.2023.10.020. Online ahead of print.

Authors

Felipe Kenji Sudo¹, Talita P Pinto², Fernanda G Q Barros-Aragao², Ivanei Bramati², Theo F Marins², Marina Monteiro², Fernanda Meireles², Rejane Soares², Pilar Erthal², Victor Calil², Naima Assuncao², Natalia Oliveira², Joana Bondarovsky², Camila Lima², Beatriz Chagas², Alana Batista², Julia Lins², Felippe Mendonca², Andrea Silveira de Souza², Fernanda C Rodrigues³, Gabriel R de Freitas⁴, Pedro Kurtz⁵, Paulo Mattos⁶, Erika C Rodrigues⁷, Fernanda G De Felice⁸, Fernanda Tovar-Moll²

Affiliations

¹ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil. Electronic address: felipe.sudo@idor.org.
² D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil.
³ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Department of Speech and Hearing Pathology, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Bloco K, 2 andar, sala 49, Cidade Universitária, 21941-902 Rio de Janeiro, RJ, Brazil.
⁴ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Department of Neurology, Fluminense Federal University (UFF), Rua Miguel de Frias, 9, Icaraí, 24220-900 Niteroi, RJ, Brazil.
⁵ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Hospital Copa Star, Rua Figueiredo de Magalhães, 700, Copacabana, 22031-012 Rio de Janeiro, RJ, Brazil; Paulo Niemeyer State Brain Institute (IECPN), R. do Rezende, 156, Centro, 20231-092, Rio de Janeiro, RJ, Brazil.
⁶ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Institute of Psychiatry, Federal University of Rio de Janeiro, Avenida Venceslau Bras, 71, fundos, Botafogo, 22290-140, Rio de Janeiro, RJ, Brazil.
⁷ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Post-Graduation Program in Rehabilitation Sciences, Centro Universitário Augusto Motta - UNISUAM, Avenida Paris, 84, Bonsucesso, 21041-020 Rio de Janeiro, RJ, Brazil.
⁸ D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Botafogo, 22281-100 Rio de Janeiro, RJ, Brazil; Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen's University, Botterell Hall, Room 563, 18 Stuart Street, Kingston ON K7L 3N6, Canada; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro: Avenida Carlos Chagas Filho, 373, Bloco B33, Cidade Universitária, 21941-902, Rio de Janeiro, RJ, Brazil.

PMID: 39492430
DOI: 10.1016/j.bbi.2023.10.020

Abstract

Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil. After months from hospital admission (mean = 168.45 ± 90.31 days; range = 75.00-365.00 days), COVID-19 survivors (n = 72) presented significant difficulties in tests tapping global cognition, episodic memory, working memory and inhibitory control relative to controls and to validated normative scores. A considerable proportion of participants suffered from fatigue (36.1 %), anxiety (27.8 %), and depressive symptoms (43.1 %). Elevated blood levels of TNF-α, during hospitalization, and TNF-α and IL-1β, at follow-up, correlated with changes in brain microstructural diffusion indices (β = 0.144, p = 0.005). These neuroimaging markers were associated with decreased episodic memory (β = -0.221, p = 0.027), working memory (β = -0.209, p = 0.034) and inhibitory control (β = -0.183, p = 0.010) at follow-up. Severity of depressive symptoms correlated with deficits in global cognition in post-COVID-19 cases (β = -0.366, p = 0.038). Our study provides preliminary evidence that long-term cognitive dysfunction following COVID-19 may be mediated by brain microstructural damage, triggered by persistent neuroinflammation. In addition, depressive symptoms may contribute to prolongated global cognitive impairments in those cases.

Keywords: COVID-19; Cognitive Dysfunction; Neuroimaging; Neuroinflammatory Diseases; Post-Acute COVID-19 Syndrome.