Neurological manifestations of long-COVID syndrome: a narrative review

Abstract

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.

Depression, Insomnia and Post-Traumatic Stress Disorder in COVID-19 Survivors: Role of Gender and Impact on Quality of Life

“…A systematic review and meta-analysis, including data from 47,910 patients, showed that up to 80% of infected patients developed at least one long-lasting symptom, including fatigue (58%), memory loss (16%), anxiety (13%) and depression (12%) [ 13 ]. Another recently published systematic review including 51 studies (n = 18,917 patients) also reported persistent problems with sleep disturbance (27%), anxiety (19%), depression PTSD (16%), and cognitive impairment (20%).…”

Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs

“…51 Emering evidence suggests that the clinical manifestations of long COVID may also be characterized by sex differences. 52–54 Our results show a cluster with predominantly hospitalized and male patients (cluster 1) and other clusters with predominantly non-hospitalized and female patients (clusters 3 and 4), which suggests that males and females may differ with respect to long COVID manifestations. A focused, prospective study could help to clarify the extent potential sex differences in long COVID.…”

The Greek Collaborative Long COVID Study: Non-Hospitalized and Hospitalized Patients Share Similar Symptom Patterns

“…As also observed in our sample, symptoms correlating to neurological and neuropsychiatric dysfunction are common, including headache, cognitive impairment, smell/taste disorders, sleep and mood disorders, myalgias, and dysautonomia, thereby representing core aspects of the Long COVID Syndrome [ 25 ]. Similarly, summarizing evidence to date, a recently published systematic review and meta-analysis, including data from 47,910 patients, showed that up to 80% of infected patients developed one or more long-lasting neuropsychiatric symptoms, including fatigue (58%), headache (44%), attention disorder (27%), ageusia (23%), anosmia (21%), memory loss (16%), anxiety (13%), and depression (12%) [ 26 ].…”