Longitudinal Neurocognitive and Pulmonological Profile of Long Covid: the COVIMMUNE-Clin Study Protocol.

Abstract

BACKGROUND\nThere is a dearth of information about brain fog , concentration, word-finding or memory problems associated with the new World Health Organization provisional classification U09.9 Post-COVID-19 Condition. Beyond this, the extent to which these symptoms may be associated with neurological, pulmonary or psychiatric difficulties is unclear.\n\n\nOBJECTIVE\nThis ongoing cohort study carefully assesses neurocognitive function in the context of neurological, psychiatric and pulmonary sequelae of COVID-19 infection among asymptomatic/mild and severe cases of COVID-19 after remission and include actively recruited healthy controls.\n\n\nMETHODS\nA total number of 150 participants will be included in this pilot study. The cohort will comprise patients after SARS-CoV-2 positive infection with either an asymptomatic course or a mild course with no symptoms except for olfactory and taste dysfunction (n=50), patients after SARS-CoV-2 positive infection with a severely affected course (n=50), and a healthy control group (n=50) with similar age and sex distribution, based on frequency matching. A comprehensive neuropsychological assessment will comprise nuanced aspects of complex attention, include language, executive function, verbal and visual learning and memory. Psychiatric, personality, social and lifestyle factors, sleep and fatigue will be evaluated. Brain magnetic resonance imaging, neurological and physical assessment and pulmonological and lung function examinations (including body plethysmography, diffusion capacity, clinical assessments and questionnaires) will also be conducted. Three visits are planned with comprehensive testing at the baseline and 12-month visit and brief neurological and neuropsychological examinations at the 6-month assessment. Blood-based biomarkers of neurodegeneration will be quantified for baseline and 12-month samples.\n\n\nRESULTS\nAt the time of submission, the study had begun recruitment, telephone and in-person screenings. The first patient was enrolled into the study at the beginning of April 2021. Interim data analysis of baseline information is expected to be complete in December 2021 and study comple-tion at the end of December 2022. Preliminary group comparisons indicate worse word list learning, verbal recall short-delayed and verbal recall long-delayed, and verbal recognition in both patient cohorts compared to the healthy control group, adjusted for age and sex. Initial volumetric compar-isons show smaller grey matter, frontal and temporal brain volumes in both patient groups com-pared to healthy controls. The results reported here are quite robust, but are not final nor put into the needed context intended at study completion.\n\n\nCONCLUSIONS\nTo the best of our knowledge this is the first study to include objective and comprehensive longitudinal analysis of neurocognitive sequelae of COVID-19 in an extreme group comparison stratified by disease severity with actively recruited healthy controls during the Pandemic. Results from this study will contribute to the nascent literature on prolonged effects on neurocognitive performance via our co-assessment of neuroradiological, neurological, pulmonary, psychiatric, and lifestyle factors.\n\n\nCLINICALTRIAL\nThis study is registered at the German Clinical Trials Registry (primary registry trial identifier: DRKS00023806; registration date: March 16, 2021, cross-referenced at World Health Organization s International Clinical Trials Registry Platform [ICTRP]).