Frontiers in Immunology (May 2023)

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers

  • Rodolfo Furlan Damiano,
  • Cristiana Castanho de Almeida Rocca,
  • Antonio de Pádua Serafim,
  • Jennifer M. Loftis,
  • Jennifer M. Loftis,
  • Leda Leme Talib,
  • Pedro Mário Pan,
  • Edecio Cunha-Neto,
  • Edecio Cunha-Neto,
  • Jorge Kalil,
  • Jorge Kalil,
  • Gabriela Salim de Castro,
  • Marilia Seelaender,
  • Bruno F. Guedes,
  • Suely K. Nagahashi Marie,
  • Heraldo Possolo de Souza,
  • Ricardo Nitrini,
  • Euripedes Constantino Miguel,
  • Geraldo Busatto,
  • Orestes V. Forlenza,
  • HCFMUSP COVID-19 Study Group,
  • Edivaldo M. Utiyama,
  • Aluisio C. Segurado,
  • Beatriz Perondi,
  • Anna Miethke-Morais,
  • Amanda C. Montal,
  • Leila Harima,
  • Solange R. G. Fusco,
  • Marjorie F. Silva,
  • Marcelo C. Rocha,
  • Izabel Marcilio,
  • Izabel Cristina Rios,
  • Fabiane Yumi Ogihara Kawano,
  • Maria Amélia de Jesus,
  • Ésper G. Kallas,
  • Carolina Carmo,
  • Clarice Tanaka,
  • Julio F. M. Marchini,
  • Carlos R. Carvalho,
  • Juliana C. Ferreira,
  • Anna Sara Levin,
  • Maura Salaroli Oliveira,
  • Thaís Guimarães,
  • Carolina dos Santos Lázari,
  • Alberto José da Silva Duarte,
  • Ester Sabino,
  • Marcello M. C. Magri,
  • Tarcisio E. P. Barros-Filho,
  • Maria Cristina Peres Braido Francisco

DOI
https://doi.org/10.3389/fimmu.2023.1174020
Journal volume & issue
Vol. 14

Abstract

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ObjectiveTo analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19.MethodsWe assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers.ResultsConcerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings.ConclusionThough we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.

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