Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives

Author:

Slama Schwok Anny1ORCID,Henri Julien2ORCID

Affiliation:

1. Sorbonne Université, INSERM U938, Biology and Cancer Therapeutics, Centre de Recherche Saint Antoine, Saint Antoine Hospital, 75231 Paris, France

2. Sorbonne Université, CNRS UMR 7238, Laboratoire de Biologie Computationnelle et Quantitative, Institut de Biologie Paris-Seine, 75005 Paris, France

Abstract

Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include a variety of symptoms, such as fatigue, loss of smell (anosmia), and neurological–cognitive sequelae, such as memory loss, anxiety, brain fog, acute encephalitis, and stroke, collectively called long neuro-COVID-19 (long neuro-COVID). They also include cardiopulmonary sequelae, such as myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, and vascular endothelial dysregulation, and the onset of new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand the mechanisms of the pathophysiologic sequelae, in particular the neurological symptoms. This mini-review presents the main mechanistic hypotheses considered to explain the multiple long neuro-COVID symptoms, namely immune dysregulation and prolonged inflammation, persistent viral reservoirs, vascular and endothelial dysfunction, and the disruption of the neurotransmitter signaling along various paths. We suggest that the nucleoprotein N of SARS-CoV-2 constitutes a “hub” between the virus and the host inflammation, immunity, and neurotransmission.

Funder

Sorbonne University and The Foundation of Sorbonne University

Publisher

MDPI AG

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