2026 ECNP Congress

EP02-2017

Long-term cognitive sequelae of severe acute respiratory syndrome coronavirus 2 infection: impact of clinical severity

Ana Barajas — G. Riquelme-Alacid, I. Sala, P. Negredo, M. Jodar, M. Sanmartí, B. Ramos · Autonomous University of Barcelona, Department of Clinical and Health Psychology, Cerdanyola del Vallès Barcelona, Spain

2026 ECNP Congress

Introduction

COVID-19 is a multisystem disease that can lead to persistent sequelae after acute phase, including cognitive impairments in post-COVID syndrome. These sequelae are common after recovery, with an estimated prevalence of 20%-26% at 3-12 months after infection [1,2]. However, literature has focused on samples with high clinical severity, which limits understanding of cognitive impact across different levels of infection severity. Furthermore, long-term follow-up studies of cognitive sequelae remain scarce, especially beyond 24 months, with evidence still heterogeneous [3]. This study aimed to evaluated long-term cognitive sequelae (24–36 months) after SARS-CoV-2 infection and the impact of clinical severity on cognitive performance.

Methods

A retrospective longitudinal cohort study was conducted with 92 patients (54 males, mean age = 54.5 years; SD = 8.5) with SARS-CoV-2 infection confirmed by positive PCR test from nasopharyngeal swab. Sociodemographic data, COVID-19 clinical severity, and cognitive performance were collected, with cognitive outcomes assessed 24–36 months after infection. Generalized linear models were conducted with cognitive performance measures as dependent variables, including severity levels (mild n = 22, moderate n = 36, severe n = 34) and premorbid IQ as covariates. Post hoc analyses were performed to explore comparisons between severity groups. Additionally, multiple linear regression analyses were conducted to evaluate predictive value of clinical severity on cognitive performance, controlling for sociodemographic variables.

Results

85.9% of patients presented deficits in at least one cognitive function, and 57.6% reported cognitive complaints. The cognitive complaints group showed poorer performance in learning (∑A1–A5 RAVLT, p=0.039), retention (A6 RAVLT, p=0.033; A7 RAVLT, p=0.039), sustained attention (CPT-IP, p<0.001), cognitive flexibility (TMT B-A, p=0.011), processing speed (Stroop-P, p=0.001; WAIS Digit Symbol Coding, p=0.001), and verbal fluency (COWAT, p=0.014). A significant effect of clinical severity of SARS-CoV-2 infection was observed on learning (∑A1–A5 RAVLT, F(2,87), p=0.003, η²=0.18) and sustained attention (CPT-IP, F(2,84), p=0.038, η²=0.08), with moderate severity group showing worst performance. Regression analyses indicated that clinical severity, particularly at moderate levels, was significantly associated with poorer performance across multiple cognitive domains (verbal memory: ∑A1–A5 RAVLT (p=0.001), A6 RAVLT, (p=0.046); A7 RAVLT (p=0.008); sustained attention: CPT-IP (p=0.035); processing speed: Stroop-P (p=0.035), Stroop-C (p=0.019), WAIS Digit Symbol Coding (p=0.016); and cognitive flexibility: TMT B-A (p=0.033), TMT B (p=0.024)), acting as predictor of long-term cognitive sequelae.

Conclusions

Cognitive dysfunction was observed as a common sequela after SARS-CoV-2 infection, with impairments in verbal memory, sustained attention, processing speed, cognitive flexibility, and verbal fluency, particularly among patients reporting cognitive complaints. In addition, clinical severity was associated with cognitive performance in a non-linear manner, with the poorest performance observed in the moderate severity group. This pattern could be partly explained by differences in clinical follow-up and intensive interventions in more severe cases, which may have mitigated cognitive impact. Consistently, the moderate group emerged as the main predictor of poorer performance in memory, attention, processing speed, and cognitive flexibility. These findings highlight the importance of integrating subjective and objective assessment in clinical practice, as well as considering infection severity when designing tailored neuropsychological follow-up and rehabilitation strategies.

References

  1. Al-Aly, Z., Davis, H., McCorkell, L., Wulf-Hanson, S., Iwasaki, A., Topol, E.J., 2024. Long COVID science, research and policy. Nat. Med. 30, 2148–2164. https://doi.org/10.1038/s41591-024-03173-6
  2. Aljadah, M., Khan, N., Beyer, A.M., Chen, Y., Blanker, A., Widlansky, M.E., 2024. Clinical implications of COVID-19-related endothelial dysfunction. JACC Adv. 3(8), 101070. https://10.1016/j.jacadv.2024.101070
  3. Barajas, A., Riquelme-Alacid, G., Vera-Montecinos, A., Ramos, B., 2026. Cognition, Cytokines, Blood–Brain Barrier, and Beyond in COVID-19: A Narrative Review. Int. J. Mol. Sci. 27 (1), 546. https://doi.org/10.3390/ijms27010546