Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations

Abstract

The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger a hyperinflammatory state characterized by elevated cytokine levels known as hypercytokinemia or cytokine storm, observed most often in severe patients. Though COVID-19 is known to be a primarily respiratory disease, neurological complications affecting both the central and peripheral nervous systems have also been reported. This review discusses potential routes of SARS-CoV-2 neuroinvasion and pathogenesis, summarizes reported neurological sequelae of COVID-19, and examines how aberrant cytokine levels may precipitate these complications. Clarification of the pathogenic mechanisms of SARS-CoV-2 is needed to encourage prompt diagnosis and optimized care. In particular, identifying the presence of cytokine storm in patients with neurological COVID-19 manifestations will facilitate avenues for treatment. Future investigations into aberrant cytokine levels in COVID-19 patients with neurological symptoms as well as the efficacy of cytokine storm-targeting treatments will be critical in elucidating the pathogenic mechanisms and effective treatments of COVID-19.

Keywords: COVID-19; Cerebrovascular disease; Coronavirus; Cytokine storm; Encephalopathy; Guillain-Barré Syndrome; Hypercytokinemia; Interferons; Neurological complications; Skeletal muscle injury.

Fig. 1

Possible pathways of SARS-CoV-2 pathogenesis causing neurological manifestations. SARS-CoV-2 may travel through an upper nasal transcribial route involving the olfactory bulb, binding to ACE2 receptors in the nasopharynx and brain and causing cytokine storm via activation of macrophages, microglia, and astrocytes. Alternatively, systemic infection and inflammation by SARS-CoV-2 can also lead to CNS and PNS manifestations if the blood–brain barrier is compromised.