Neuropathology of COVID-19 (neuro-COVID): clinicopathological update

  • Jerry J. Lou Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA
  • Mehrnaz Movassaghi Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Dominique Gordy Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Madeline G. Olson Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Ting Zhang Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Maya S. Khurana Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA
  • Zesheng Chen Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Mari Perez-Rosendahl Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA
  • Samasuk Thammachantha Department of Pathology, Prasat Neurological Institute, Thailand
  • Elyse J. Singer Department of Neurology, David Geffen School of Medicine at UCLA, USA
  • Shino D. Magaki Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
  • Harry V. Vinters Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, USA
  • William H. Yong Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA
Keywords: CNS, COVID-19, SARS-CoV-2, Brain, Pituitary

Abstract

Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21st century. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single-stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved. In Western clinical studies, relatively mild neurological dysfunction such as anosmia and dysgeusia is frequent (~70-84%) while severe neurologic disorders such as stroke (~1-6%) and meningoencephalitis are less common. It is unclear how much SARS-CoV-2 infection contributes to the incidence of stroke given co-morbidities in the affected patient population. Rarely, clinically-defined cases of acute disseminated encephalomyelitis, Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in COVID-19 patients. Common neuropathological findings in the 184 patients reviewed include microglial activation (42.9%) with microglial nodules in a subset (33.3%), lymphoid inflammation (37.5%), acute hypoxic-ischemic changes (29.9%), astrogliosis (27.7%), acute/subacute brain infarcts (21.2%), spontaneous hemorrhage (15.8%), and microthrombi (15.2%). In our institutional cases, we also note occasional anterior pituitary infarcts. COVID-19 coagulopathy, sepsis, and acute respiratory distress likely contribute to a number of these findings. When present, central nervous system lymphoid inflammation is often minimal to mild, is detected best by immunohistochemistry and, in one study, indistinguishable from control sepsis cases. Some cases evince microglial nodules or neuronophagy, strongly supporting viral meningoencephalitis, with a proclivity for involvement of the medulla oblongata. The virus is detectable by reverse transcriptase polymerase chain reaction, immunohistochemistry, or electron microscopy in human cerebrum, cerebellum, cranial nerves, olfactory bulb, as well as in the olfactory epithelium; neurons and endothelium can also be infected. Review of the extant cases has limitations including selection bias and limited clinical information in some cases. Much remains to be learned about the effects of direct viral infection of brain cells and whether SARS-CoV-2 persists long-term contributing to chronic symptomatology.

Author Biographies

Jerry J. Lou, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA

M.D. (2020)

Mehrnaz Movassaghi, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

M.D., Visiting Scientist

Dominique Gordy, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

Undergraduate student

Madeline G. Olson, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

Post-baccalaureate

Ting Zhang, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

M.D., Resident in Pathology

Maya S. Khurana, Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA

Undergraduate student

Zesheng Chen, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

Neuropathology Fellow

Mari Perez-Rosendahl, Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA

Assistant Professor (Neuropathology)

Samasuk Thammachantha, Department of Pathology, Prasat Neurological Institute, Thailand

Neuropathologist, Thailand

Elyse J. Singer, Department of Neurology, David Geffen School of Medicine at UCLA, USA

Professor (Neuroinfectious Diseases)

Shino D. Magaki, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA

Assistant Professor (Neuropathology)

Harry V. Vinters, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, USA

Professor Emeritus, UCLA

William H. Yong, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA; Department of Pathology and Laboratory Medicine, University of California - Irvine School of Medicine, USA

M.D., Professor (Department of Pathology and Laboratory Medicine, UC Irvine)

Published
2021-01-18
How to Cite
Lou, J. J., Movassaghi, M., Gordy, D., Olson, M. G., Zhang, T., Khurana, M. S., Chen, Z., Perez-Rosendahl, M., Thammachantha, S., Singer, E. J., Magaki, S. D., Vinters, H. V., & Yong, W. H. (2021). Neuropathology of COVID-19 (neuro-COVID): clinicopathological update. Free Neuropathology, 2, 2. https://doi.org/10.17879/freeneuropathology-2021-2993
Section
Review