Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

Version 1 : Received: 25 June 2020 / Approved: 26 June 2020 / Online: 26 June 2020 (17:32:55 CEST)

How to cite: Murta, V.; Villarreal, A.; Ramos, A.J. SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?. Preprints 2020, 2020060319 (doi: 10.20944/preprints202006.0319.v1). Murta, V.; Villarreal, A.; Ramos, A.J. SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?. Preprints 2020, 2020060319 (doi: 10.20944/preprints202006.0319.v1).

Abstract

With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

Subject Areas

glia; central nervous system; COVID-19; SARS; MERS; coronavirus

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