AUTHOR=Matos Aline de Moura Brasil , Dahy Flavia Esper , de Moura João Victor Luisi , Marcusso Rosa Maria Nascimento , Gomes Andre Borges Ferreira , Carvalho Fernanda Martins Maia , Fernandes Gustavo Bruniera Peres , Felix Alvina Clara , Smid Jerusa , Vidal Jose Ernesto , Frota Norberto Anizio Ferreira , Casseb Jorge , Easton Ava , Solomon Tom , Witkin Steven S. , Malta Romano Camila , de Oliveira Augusto César Penalva ,  NeuroCovBR Study Group 

TITLE=Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.678924

DOI=10.3389/fneur.2021.678924

ISSN=1664-2295

ABSTRACT=Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVD-19 who developed subacute cognitive disturbances. 
Methods: From June 1st  to August 15th 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and the Clock Drawing Test (CDT). 
Results: All but one of our patients were female and mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15-33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of 6 words/min (IQR 5.25-10.75) and altered visuospatial construction with a median of 4 points (IQR 4-9) (CDT). CSF pleocytosis was not detected and only one patient was positive for SARS-CoV-2 by RT-PCR in her CSF. Oligoclonal bands and IgG index were not indicative of intrathecal antibody production.
Conclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.