NEUROLOGICAL RISKS AND BENEFITS OF CYTOKINE-BASED TREATMENTS IN
COVID-19: A JOURNEY FROM PRECLINICAL TO CLINICAL EVIDENCE
Abstract
IImmunodeficiency and hyperinflammation characterize COVID-19 associated
states; thus, repurposing of multiple cytokine and/or anti-cytokine
drugs currently being used in other therapeutic areas has been suggested
as a potential therapeutic strategy in COVID-19 patients. Clinical
trials involving these drugs target the most frequent and
life-threatening peripheral consequences of the disease, mainly focusing
on lung, heart, and coagulation functions; however, a growing number of
reports describe a wide range of COVID-associated neurological
manifestations (altogether defined as neuro-COVID) including anosmia,
seizures, confusion, stroke, encephalopathy, and paralysis. Notably, the
underlying pathophysiological mechanisms for neuro-COVID may also
include dysregulation of cytokines/chemokines, deficiencies in the
innate immune response, and autoimmunity. This suggests that therapeutic
attempts with drugs targeting cytokine-mediated inflammation in
peripheral organs could also positively affect neuro-COVID
manifestations. As a matter of fact, some of these drugs have also been
scrutinized for their potential efficacy in treating neuroinflammatory
diseases such as optic neuromyelitis, epilepsy, stroke, and traumatic
brain injury, among others. On the other hand, anti-cytokine drugs, by
impairing relevant physiological activities exerted by these mediators
in the CNS, may also be endowed with significant neurological risk.
Therefore, the primary aim of the present manuscript is to review the
available preclinical and clinical data regarding the neurological
effects of the drugs targeting cytokine-mediated inflammation, in order
to raise awareness about their potentially beneficial or detrimental
neurological consequences when used to treat COVID-19 patients.