Neurological manifestations of long-COVID syndrome: a narrative review

Maria-Ioanna Stefanou; Lina Palaiodimou; Eleni Bakola; Nikolaos Smyrnis; Marianna Papadopoulou; George P Paraskevas; Emmanouil Rizos; Eleni Boutati; Nikolaos Grigoriadis; Christos Krogias; Sotirios Giannopoulos; Sotirios Tsiodras; Mina Gaga; Georgios Tsivgoulis

doi:10.1177/20406223221076890

Neurological manifestations of long-COVID syndrome: a narrative review

Ther Adv Chronic Dis. 2022 Feb 17:13:20406223221076890. doi: 10.1177/20406223221076890. eCollection 2022.

Authors

Affiliations

¹ Second Department of Neurology, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
² Second Department of Psychiatry, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
³ Second Department of Neurology, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece; Department of Physiotherapy, University of West Attica, Athens, Greece.
⁴ Second Propaedeutic Department of Internal Medicine and Research Institute, University General Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
⁵ Second Department of Neurology, 'AHEPA' University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁶ Department of Neurology, St. Josef-Hospital Bochum, Ruhr University Bochum, Bochum, Germany.
⁷ 4th Department of Internal Medicine, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁸ 7th Respiratory Medicine Department and Asthma Center, Athens Chest Hospital 'Sotiria', Athens, Greece.
⁹ Second Department of Neurology, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece. Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.

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.

Keywords: COVID-19; SARS-CoV-2; long-COVID; long-haul; neurological manifestations; post-acute sequelae of SARS-CoV-2.

Publication types

Review