Neurological risks and benefits of cytokine-based treatments in coronavirus disease 2019: from preclinical to clinical evidence.

Immunodeficiency and hyperinflammation are responsible for the most frequent and life-threatening forms of coronavirus disease 2019 (COVID-19). Therefore, cytokine-based treatments targeting immuno-inflammatory mechanisms are currently undergoing clinical scrutiny in COVID-19-affected patients. In addition, COVID-19 patients also exhibit a wide range of neurological manifestations (neuro-COVID), which may also benefit from cytokine-based treatments. In fact, such drugs have shown some clinical efficacy also in neuroinflammatory diseases. On the other hand, anti-cytokine drugs are endowed with significant neurological risks, mainly attributable to their immunodepressant effects. Therefore, the aim of the present manuscript is to briefly describe the role of specific cytokines in neuroinflammation, to summarize the efficacy in preclinical models of neuroinflammatory diseases of drugs targeting these cytokines and to review the clinical data regarding the neurological effects of these drugs currently being investigated against COVID-19, in order to raise awareness about their potentially beneficial and/or detrimental neurological consequences. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.

Neurobiology of coronaviruses: Potential relevance for COVID-19.

In the first two decades of the 21st century, there have been three outbreaks of severe respiratory infections caused by highly pathogenic coronaviruses (CoVs) around the world: the severe acute respiratory syndrome (SARS) by the SARS-CoV in 2002-2003, the Middle East respiratory syndrome (MERS) by the MERS-CoV in June 2012, and Coronavirus Disease 2019 (COVID-19) by the SARS-CoV-2 presently affecting most countries In all of these, fatalities are a consequence of a multiorgan dysregulation caused by pulmonary, renal, cardiac, and circulatory damage; however, COVID patients may show significant neurological signs and symptoms such as headache, nausea, vomiting, and sensory disturbances, the most prominent being anosmia and ageusia. The neuroinvasive potential of CoVs might be responsible for at least part of these symptoms and may contribute to the respiratory failure observed in affected patients. Therefore, in the present manuscript, we have reviewed the available preclinical evidence on the mechanisms and consequences of CoVs-induced CNS damage, and highlighted the potential role of CoVs in determining or aggravating acute and long-term neurological diseases in infected individuals. We consider that a widespread awareness of the significant neurotropism of CoVs might contribute to an earlier recognition of the signs and symptoms of viral-induced CNS damage. Moreover, a better understanding of the cellular and molecular mechanisms by which CoVs affect CNS function and cause CNS damage could help in planning new strategies for prognostic evaluation and targeted therapeutic intervention.