How to detect and track chronic neurologic sequelae of COVID-19? Use of auditory brainstem responses and neuroimaging for long-term patient follow-up

Abstract

This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.

Keywords: Auditory brainstem responses; Brainstem dysfunction; COVID-19; Cytokine storm; Microglia priming; Multiple sclerosis; Neuroimaging; Neuroinflammatory mechanisms; Neurologic sequelae; SARS-CoV-2.

Fig. 1

Long-term follow-up of COVID-19 patients predisposed to chronic neurologic sequelae. COVID-19 patients that are either admitted to ICU for severe respiratory failure or exhibit neurologic symptoms at initial diagnosis may be considered as having more risks for developing chronic neuroinflammation and brain cell degeneration due to infection. This may also be true for confirmed COVID-19 patients suffering from pre-existing conditions associated with chronic neuroinflammation. Patients exhibiting these characteristics should be submitted to a long-term neurologic follow-up protocol to ensure complete recovery. Auditory brainstem responses, neuroinflammation imaging and routine cognitive evaluation may be used for follow-up examination, as they might help assess existing or emerging brain dysfunction and objectivize further treatment. Abbreviations: ICU, Intensive Care Units; MRI, Magnetic resonance imaging; PET, Positron Emission Tomography; TBI, Traumatic Brain Injury.