SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations

Joy Mitra, Manohar Kodavati, Vincent E. Provasek, K. S. Rao, Sankar Mitra, Dale J. Hamilton, Philip J. Horner, Farhaan S. Vahidy, Gavin W. Britz, Thomas A. Kent, Muralidhar L. Hegde

Research output: Contribution to journalReview articlepeer-review

Abstract

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to impact our lives by causing widespread illness and death and poses a threat due to the possibility of emerging strains. SARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) before entering vital organs of the body, including the brain. Studies have shown systemic inflammation, cellular senescence, and viral toxicity-mediated multi-organ failure occur during infectious periods. However, prognostic investigations suggest that both acute and long-term neurological complications, including predisposition to irreversible neurodegenerative diseases, can be a serious concern for COVID-19 survivors, especially the elderly population. As emerging studies reveal sites of SARS-CoV-2 infection in different parts of the brain, potential causes of chronic lesions including cerebral and deep-brain microbleeds and the likelihood of developing stroke-like pathologies increases, with critical long-term consequences, particularly for individuals with neuropathological and/or age-associated comorbid conditions. Our recent studies linking the blood degradation products to genome instability, leading to cellular senescence and ferroptosis, raise the possibility of similar neurovascular events as a result of SARS-CoV-2 infection. In this review, we discuss the neuropathological consequences of SARS-CoV-2 infection in COVID survivors, focusing on possible hemorrhagic damage in brain cells, its association to aging, and the future directions in developing mechanism-guided therapeutic strategies.

Original languageEnglish (US)
Article number101687
JournalAgeing Research Reviews
Volume80
DOIs
StatePublished - Sep 2022

Keywords

  • Brain fog
  • COVID-19
  • Coronavirus
  • Ferroptosis
  • Genome instability
  • Hemorrhage
  • SARS-CoV-2
  • Senescence
  • COVID-19/complications
  • Humans
  • Nervous System Diseases/pathology
  • Aged
  • Brain/metabolism

ASJC Scopus subject areas

  • Neurology
  • Aging
  • Molecular Biology
  • Biochemistry
  • Biotechnology

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