Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort.

Background and purpose Neurological complications of SARS-CoV-2 infection are noticed among critically-ill patients soon after disease onset. Information on delayed neurological sequelae of SARS-CoV-2 infection is nil. Following a longitudinal study design, we assessed the occurrence of cognitive decline among individuals with a history of mild symptomatic SARS-CoV-2 infection. Methods Stroke- and seizure-free Atahualpa residents aged ≥40 years who had pre-pandemic cognitive assessments as well as normal brain MRI and EEG recordings, underwent repeated evaluations six months after a SARS-CoV-2 outbreak infection in Atahualpa. Patients requiring oxygen therapy, hospitalization, and those who had initial neurological manifestations were excluded. Cognitive decline was defined as a reduction in Montreal Cognitive Assessment (MoCA) score between the post-pandemic and pre-pandemic assessments that was ≥4 points than the reduction observed between two pre-pandemic MoCAs. The relationship between SARS-CoV-2 infection and cognitive decline was assessed by fitting logistic mixed models for longitudinal data as well as exposure-effect models. Results Of 93 included individuals (mean age: 62.6±11 years), 52 (56%) had a history of mild symptomatic SARS-CoV-2 infection. Post-pandemic MoCA decay was worse in seropositive individuals. Cognitive decline was recognized in 11/52 (21%) seropositive and 1/41 (2%) seronegative individuals. In multivariate analyses, the odds for developing cognitive decline was 18.1 times higher among SARS-CoV-2 seropositive individuals (95% C.I.: 1.75 - 188; p=0.015). Exposure-effects models confirmed this association (β: 0.24; 95% C.I.: 0.07 - 0.41; p=0.006). Conclusions This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown.