| Summary: | Abstract The COVID-19 infection is assumed to induce cognitive failure. Identifying the relationship between COVID-19, the effect of vaccination and medication, and accommodating non-COVID-19 factors to cognitive failure is essential. This study was conducted in Indonesia from September 2021 to January 2023. Demographic information, clinical data, comorbidities, vaccination, and medication during COVID-19 were obtained, as well as a 6-month cognitive assessment with Cognitive Failures Questionnaire/CFQ, Fatigue Severity Score, and Generalized Anxiety Disorder (GAD-7). A Structural Equation Model explains the relationship between potential predictors and cognitive failure. The average score of CFQ after 6 months was 45.6 ± 23.1 out of 100. The severity of the disease, which was associated with vaccination status, age, previous infection, and unit of treatment (p < 0.05), was not related to cognitive failure (p = 0.519), although there is a significant direct impact of worst vaccination status to cognitive failure(p < 0.001). However, age, fatigue, and current anxiety were associated with higher cognitive failure (p < 0.001), although comorbidities and recent headaches were not significant in other models (p > 0.05). This study concludes that cognitive failure after COVID-19 is a multifactorial event and does not solely depend on COVID-19 severity. It is crucial to re-address the factors related to the long-term efficacy of vaccination and medication and focus on non-health factors affecting cognitive failure. Trial Registration: NCT05060562.
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