Neuropsychiatric Presentations and Sequelae of COVID-19: Current Evidence and Research Recommendations

Document Type : Letter to Editor


1 School of Medicine, National University of Ireland Galway, Galway, Ireland

2 School of Medicine and Health Science, University College Dublin, Dublin, Ireland



Global pandemics compel us to contemplate the lessons of history. The influenza pandemic of 1918-1920 gave rise to the curious neurological syndrome of encephalitis lethargica, which left its unfortunate victims with varying combinations of motionlessness, hypersomnolence, and ophthalmoplegia. There is increasing awareness during the current pandemic of coronavirus disease 2019 (COVID-19) of a range of neurologic and psychiatric manifestations which in some cases are the presenting clinical features of the infection. Furthermore, patients with chronic neurologic conditions such as multiple sclerosis are susceptible to more severe COVID-19 by virtue of their use of immunosuppressant medications.1Some of the anti-viral drugs used in the management of COVID-19, such as remdesivir, are also known to have adverse effects which involve the nervous system.2Increased public and physician awareness of these neuropsychiatric phenomena may aid in their earlier diagnosis and management.

A variety of neurologic symptoms have been described in patients infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Headache, vertigo, ataxia, reduced consciousness and seizures are among the most commonly reported symptoms arising from involvement of the central nervous system.3Guillain-Barré syndrome, an acute polyradiculopathy presenting with flaccid ascending limb weakness, has also been described.4Agarwal et al published a case series of five patients with diverse manifestations of CNS involvement, including two 41-year-old females, one with limb weakness and aphasia resulting from an ischaemic stroke, and the other with internuclear ophthalmoplegia secondary to oedema of the corpus callosum.2

Anosmia may result from rhinitis secondary to respiratory viruses including influenza. Early in the COVID-19 pandemic, this symptom emerged as one of its more prominent presenting features, sometimes in the absence of other clinical features. A cross-sectional study from Spain found that smell and/or taste dysfunction were at least two-fold more common in COVID-19 patients than in controls.5This chemosensory impairment mainly afflicted younger patients who did not require hospitalisation. Subclinical deficits in olfaction demonstrated by quantitative smell testing have been proposed as a sensitive biomarker for COVID-19.6Given that olfactory receptor cells do not express the angiotensin-converting enzyme 2 (ACE2) receptor exploited by this novel coronavirus, multiple pathogenetic mechanisms for these sensory deficits have been proposed which will stimulate further investigation.

COVID-related cerebrovascular disease, in the form of ischaemic stroke, intracerebral haemorrhage and cerebral dural venous sinus thrombosis, result primarily from large vessel disease and are believed to be a reflection of the pro-thrombotic state caused by the endothelial damage from SARS-CoV-2 infection.4Many of the most severely ill COVID-19 patients present other risk factors for cerebrovascular disease such as diabetes, obesity and hypertension. Some of the improvement in survival rates among hospitalised COVID-19 patients may be attributed to the increased use of antiplatelet agents and anticoagulants in this patient cohort as clinical experience with this virus increases (Read more…)