Prevalence and long-term outcomes of brain fog and cognitive impairment in individuals with long COVID: A systematic review

BACKGROUND: Long COVID is increasingly recognized as a complex multisystem condition, with brain fog and cognitive impairment emerging as some of its manifestations. Despite growing literature, the pooled prevalence, subgroup differences, and underlying mechanisms remain incompletely understood. METHODS: We systematically reviewed 47 studies (2000-2025) encompassing over 25,000 patients to evaluate the prevalence of brain fog and cognitive impairment among long COVID populations. Data were extracted on study design, patient demographics, follow-up duration, and subgroup variables including gender, hospitalization, vaccination, and geographic region. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS v9.0) and JBI checklists. Quantitative synthesis was performed with subgroup and temporal analyses, presented in forest plots and summary figures. RESULTS: The pooled prevalence of brain fog was 30% (95% CI: 28-32), while cognitive impairment was 25% (95% CI: 23-27). Female patients consistently showed higher rates compared to males (34% vs 23% for brain fog; 29% vs 21% for cognitive impairment). Community-managed patients demonstrated higher prevalence compared to hospitalized cohorts, and unvaccinated individuals had a greater burden than vaccinated ones. Temporal analyses indicated that prevalence increased with longer follow-up, suggesting symptom persistence or late manifestation. Pathophysiological explanations include neuroinflammation, microvascular injury, immune dysregulation, and psychosocial stressors. CONCLUSION: Brain fog and cognitive impairment are common, persistent, and clinically significant features of long COVID. Gender differences, vaccination status, and follow-up duration influence prevalence. Future studies should focus on mechanisms, preventive strategies, and targeted interventions to mitigate long-term cognitive sequelae.