2026 ECNP Congress

PS01-1163

Long-term cognitive sequelae in COVID-19 patients: Differences according to acute-phase C-reactive protein levels

Ana Barajas — P. Negredo, M. Jodar, G. Riquelme Alacid, F. Vidal Domenech, M. Sanmarti, V. Ferrer Diaz De Brito Fernandez, A. Marron, E. Grasa, B. Ramos · Universitat Autònoma de Barcelona, Clinical and Health Psychology Department, Bellaterra- Barcelona, Spain

2026 ECNP Congress

Introduction

Cognitive deficits are among the most frequent manifestations in patients with post-COVID-19 sequelae, with studies reporting that up to 70% of individuals experience persistent cognitive complaints after infection [1]. These cognitive impairments may persist for months or even years, affecting daily functioning and quality of life. Neuroinflammatory processes during the acute phase of SARS-CoV-2 infection may be a key mechanism underlying these long-term sequelae, potentially via disruption of the blood-brain barrier [2]. C-reactive Protein (CRP), a widely used inflammatory marker, has been consistently associated with disease severity, including in patients with COVID-19 [3], and may reflect the magnitude of the systemic inflammatory response. Its relationship with long-term cognitive outcomes remains insufficiently understood. Objective:To analyse differences in long-term cognitive performance between patients with higher versus lower C-reactive protein (CRP) levels during the acute phase of SARS-CoV-2 infection. Method:Seventy-nine patients participated in this multicentre, observational, prospective study. Participants were recruited from three hospitals in Catalonia and assessed 2-3 years after infection. Blood samples collected during the acute phase were used to determine inflammatory markers (through CRP levels). A comprehensive neuropsychological battery was administered 2-3 years after the infection to assess attention, memory, executive functions, and language using standardized tests. Participants were classified into two groups (lower CRP: n=28; higher CRP: n=51) based on a previously reported prognostic threshold of 41.4 mg/L [4]. Group comparisons were performed, and linear regression models were conducted to examine associations between CRP and cognitive performance, adjusting for age and sex. Results:Patients with higher CRP levels showed significantly worse performance in verbal memory, specifically in long-term recognition (Rey Auditory Verbal Learning Test (RAVLT) recognition task; β = -6.77, p = 0.002, p_FDR = 0.049), and attention (CPT-IP; β = -7.14, p = 0.005, p_FDR = 0.049), compared with those with lower CRP levels. A trend towards poorer performance was also observed in semantic verbal fluency (β = -7.62, p = 0.007, p_FDR = 0.055). Complementary regression analyses showed significant associations between CRP levels and memory, attentional, and executive measures, including the RAVLT recognition task, Trail Making Test – Part A, Trail Making Test – Part B, and semantic fluency, reinforcing the role of inflammation in these domains. However, these differences did not remain significant after correction for multiple comparisons in linear regression models adjusted for age and sex.Conclusion:Neuroinflammatory processes associated with SARS-CoV-2 infection may contribute to persistent cognitive sequelae. Our findings suggest a potential association between higher acute-phase inflammatory burden and long-term cognitive outcomes, particularly in attention and memory, two of the most consistently affected domains in post-COVID populations [5]. These results support the relevance of inflammatory markers as potential indicators of long-term cognitive vulnerability following COVID-19 and highlight the need for further longitudinal research to clarify their predictive value and its clinical applicability.

Keywords:SARS-CoV-2, C-reactive protein, Neuroinflammation, COVID-19 sequelae, Neuropsychology.

References

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