Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

Alberto Paniz-Mondolfi, Clare Bryce, Zachary Grimes, Ronald E Gordon, Jason Reidy, John Lednicky, Emilia Mia Sordillo, Mary Fowkes, Alberto Paniz-Mondolfi, Clare Bryce, Zachary Grimes, Ronald E Gordon, Jason Reidy, John Lednicky, Emilia Mia Sordillo, Mary Fowkes

Abstract

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.

Keywords: CNS infection; SARS-CoV-2; endothelium; neuroinvasion; neurotropism.

Conflict of interest statement

All the authors declare that there are no conflict of interests.

© 2020 Wiley Periodicals LLC.

Figures

Figure 1
Figure 1
A, Brain capillary endothelial cells showing virus particles within cytoplasmic vacuoles (← arrow) B, Blebbing of viral particles coming in/out of the endothelial cell wall (circles) The relationship of virus particles (arrows←) to the endothelial cells (virus ingress/egress) is depicted. Note the dense inner core and densely stained periphery of viral particles. C, Endothelial neural cell interface showing a cytoplasmic vacuole filled with viral particles in various stages of bud formation (arrow←) adjacent to the basement membrane within the neural cell (frontal lobe). D, Neural intracytoplasmic vesicle showing viral‐like particles. Insert: Detail on viral particle exhibiting electron dense centers with distinct stalk‐like peplomeric projections. Scale bars are shown at the bottom left/right of each figure. BM, basement membrane; EC, endothelial cells; IV, intracytoplasmic vesicles; NT, neural tissue; RBC, red blood cell

References

    1. Gorbalenya AE, Baker SC, Baric RS, et al. The species severe acute respiratory syndrome‐related coronavirus: classifying 2019‐nCoV and naming it SARS‐CoV‐2. Nat Microbiol. 2020;5:536‐544. 10.1038/s41564-020-0695-z
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497‐506.
    1. Baig AM. Neurological manifestations in COVID‐19 caused by SARS‐CoV‐2. CNS Neurosci Ther. 2020;00:1‐3.
    1. Desforges M, Le Coupanec A, Dubeau P, et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12:14.
    1. Bohmwald K, Gálvez N, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci. 2018;12:386. 10.3389/fncel.2018.00386
    1. Rhoades RE, Tabor‐Godwin JM, Tsueng G, Feuer R. Enterovirus infections of the central nervous system. Virology. 2011;411(2):288‐305. 10.1016/j.virol.2010.12.014
    1. Dawes BE, Freiberg AN. Henipavirus infection of the central nervous system. Pathog Dis. 2019;77(2):ftz023. 10.1093/femspd/ftz023
    1. Foley JE, Rand C, Leutenegger C. Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. J Feline Med Surgery. 2003;5:313‐322.
    1. Greig AS, Mitchell D, Corner AH, Bannister GL, Meads EB, Julian RJ. A hemagglutinating virus producing encephalomyelitis in baby pigs. Can J Comp Med Vet Sci. 1962;26:49‐56.
    1. Cowley TJ, Weiss SR. Murine coronavirus neuropathogenesis: determinants of virulence. J Neurovirol. 2010;16:427‐434.
    1. Yin R, Feng W, Wang T, et al. Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019 [published online ahead of print April 15, 2020]. J Med Virol. 2020. 10.1002/jmv.25888
    1. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS‐coronavirus‐2. Int J Infect Dis. 2020;94:55‐58. 10.1016/j.ijid.2020.03.062
    1. Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS‐CoV‐2 infection [published online ahead of print April 15, 2020]. N Engl J Med. 2020. 10.1056/NEJMc2008597
    1. DeBiasi RL, Tyler KL. Polymerase chain reaction in the diagnosis and management of central nervous system infections. Arch Neurol. 1999;10:1215‐1219.
    1. Gu J, Gong E, Zhang B, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202:415‐424.
    1. Oshiro LS, Schieble JH, Lennette EH. Electron microscopic studies of coronavirus. J Gen Virol. 1971;12:161‐168.
    1. Hocke AC, Becher A, Knepper J, et al. Emerging human Middle East respiratory syndrome coronavirus causes widespread infection and alveolar damage in human lungs. Am J Resp Crit Care Med. 2013;188:882‐886.
    1. Hamming I, Timens W, Bulthuis MLC, et al. Neurologic features in severe SARS‐CoV‐2 infection [published online ahead of print April 15, 2020]. N Engl J Med. 2020. 10.1056/NEJMc2008597
    1. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients [published online ahead of print February 27, 2020]. J Med Virol. 2020. 10.1002/jmv.25728

Source: PubMed

3
Subscribe