Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19)

Abstract

BackgroundEvidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson’s disease (PD) and dementia up to 6 and 12 months after infection, respectively. Longer follow-ups with comparison groups are needed to clarify the potentially increased risk of neurodegenerative diseases in COVID-19 survivors, namely those infected before mass vaccination.MethodsA prospective study started in July 2022 with four cohorts of 150 individuals each, defined according to SARS-CoV-2 infection and hospitalisation status between March 2020 and February 2021: cohort 1—hospitalised due to SARS-CoV-2 infection; cohort 2—hospitalised, COVID-19-free; cohort 3—infected, not hospitalised; cohort 4—not infected, not hospitalised. Cohort 2 will be matched to cohort 1 according to age, sex, level of hospitalisation care and length of stay; cohort 4 will be age-matched and sex-matched to cohort 3. Baseline, 1-year and 2-year follow-up evaluations will include: cognitive performance assessed with the Montreal Cognitive Assessment (MoCA) and neuropsychological tests; the assessment of prodromal markers of PD with Rapid Eye Movement Sleep Behaviour Disorder single-question Screen and self-reported olfactory and gustative alterations; screening of PD with the 9-item PD screening questionnaire; gait evaluation with Timed Up&Go test. Suspected cases of cognitive impairment and PD will undergo a clinical evaluation by a neurologist. Frequency measures of neurological complications, prodromal markers and diagnoses of dementia and PD, will be presented. The occurrence of cognitive decline—the difference between baseline and 1-year MoCA scores 1.5 SD below the mean of the distribution of the variation—will be compared between cohorts 1 and 2, and cohorts 3 and 4 with OR estimated using multivariate logistic regression.Ethics and disseminationThis study received ethics approval from the Ethics Committees of the health units Unidade Local de Saúde de Matosinhos and Centro Hospitalar de Entre Douro e Vouga, and informed consent is signed for participating. Results will be disseminated among the scientific community and the public.

A Comprehensive Review on Navigating the Neurological Landscape of COVID-19: Insights Into Etiopathogenesis and Clinical Management

“…This correlation is supported by evidence from various studies, encompassing in vivo, in vitro, and animal research, suggesting the potential neuroinvasive nature of the novel COVID-19 virus [46]. Additionally, specific prodromal indicators, such as impaired olfaction and rapid eye movement (REM) sleep behavior disorder, have been identified as potential predictors of Parkinson's disease and dementia [46]. These findings underscore the need for continued vigilance and comprehensive monitoring of neurological sequelae in individuals recovering from COVID-19 infection.…”

“…Furthermore, neurological symptoms after COVID-19 have been linked with alterations in brain microstructure observed on imaging examinations. This correlation is supported by evidence from various studies, encompassing in vivo, in vitro, and animal research, suggesting the potential neuroinvasive nature of the novel COVID-19 virus [46]. Additionally, specific prodromal indicators, such as impaired olfaction and rapid eye movement (REM) sleep behavior disorder, have been identified as potential predictors of Parkinson's disease and dementia [46].…”

“…A meta-analysis revealed that individuals with severe COVID-19 manifestations faced elevated odds of experiencing persistent symptoms such as headache, fatigue, myalgia, anosmia, and dysgeusia long after the acute phase of the infection [45]. Moreover, another study indicated that long-lasting neurological complications could impact up to 45% of both hospitalized and non-hospitalized COVID-19 survivors, with fatigue and cognitive complaints emerging as the most prevalent issues [46]. Furthermore, there have been associations between COVID-19 and neurodegenerative complications like parkinsonism and dementia, with heightened risks observed within the six months following infection [3].…”

“…Furthermore, there have been associations between COVID-19 and neurodegenerative complications like parkinsonism and dementia, with heightened risks observed within the six months following infection [3]. A study highlighted a notable decline in cognitive function among individuals infected with SARS-CoV-2, as evidenced by a four-point reduction in the Montreal Cognitive Assessment (MoCA) from pre-pandemic to post-pandemic evaluations [46]. Furthermore, neurological symptoms after COVID-19 have been linked with alterations in brain microstructure observed on imaging examinations.…”

A Comprehensive Review of Neurodegenerative Manifestations of SARS-CoV-2

“…The amalgamation of these mechanisms significantly heightens the risk of long-term neurological consequences in survivors [ 27 ]. Such consequences may result from the exacerbation of pre-existing neurological disorders or the onset of new ones.…”