tetano
Editor, Senior Moderator
Neuron
. 2022 Nov 10;S0896-6273(22)01028-5.
doi: 10.1016/j.neuron.2022.11.007. Online ahead of print.
Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients
Mona Khan[SUP] 1 [/SUP], Marnick Clijsters[SUP] 2 [/SUP], Sumin Choi[SUP] 1 [/SUP], Wout Backaert[SUP] 3 [/SUP], Michiel Claerhout[SUP] 4 [/SUP], Floor Couvreur[SUP] 4 [/SUP], Laure Van Breda[SUP] 4 [/SUP], Florence Bourgeois[SUP] 5 [/SUP], Kato Speleman[SUP] 5 [/SUP], Sam Klein[SUP] 6 [/SUP], Johan Van Laethem[SUP] 7 [/SUP], Gill Verstappen[SUP] 8 [/SUP], Ayse Sumeyra Dereli[SUP] 1 [/SUP], Seung-Jun Yoo[SUP] 9 [/SUP], Hai Zhou[SUP] 1 [/SUP], Thuc Nguyen Dan Do[SUP] 10 [/SUP], Dirk Jochmans[SUP] 10 [/SUP], Lies Laenen[SUP] 11 [/SUP], Yves Debaveye[SUP] 12 [/SUP], Paul De Munter[SUP] 13 [/SUP], Jan Gunst[SUP] 12 [/SUP], Mark Jorissen[SUP] 14 [/SUP], Katrien Lagrou[SUP] 15 [/SUP], Philippe Meersseman[SUP] 13 [/SUP], Johan Neyts[SUP] 10 [/SUP], Dietmar Rudolf Thal[SUP] 16 [/SUP], Vedat Topsakal[SUP] 8 [/SUP], Christophe Vandenbriele[SUP] 17 [/SUP], Joost Wauters[SUP] 13 [/SUP], Peter Mombaerts[SUP] 18 [/SUP], Laura Van Gerven[SUP] 19 [/SUP]
Affiliations
Abstract
Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.
Keywords: COVID-19; Coronavirus; Delta; Omicron; RNAscope; SARS-CoV-2; Virchow-Robin space; blood-brain barrier; brain parenchyma; frontal lobe; glia limitans perivascularis; leptomeninges; neuroinvasion; neurotropism; olfactory; olfactory bulb; olfactory sensory neuron; perineurial olfactory nerve fibroblast.
. 2022 Nov 10;S0896-6273(22)01028-5.
doi: 10.1016/j.neuron.2022.11.007. Online ahead of print.
Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients
Mona Khan[SUP] 1 [/SUP], Marnick Clijsters[SUP] 2 [/SUP], Sumin Choi[SUP] 1 [/SUP], Wout Backaert[SUP] 3 [/SUP], Michiel Claerhout[SUP] 4 [/SUP], Floor Couvreur[SUP] 4 [/SUP], Laure Van Breda[SUP] 4 [/SUP], Florence Bourgeois[SUP] 5 [/SUP], Kato Speleman[SUP] 5 [/SUP], Sam Klein[SUP] 6 [/SUP], Johan Van Laethem[SUP] 7 [/SUP], Gill Verstappen[SUP] 8 [/SUP], Ayse Sumeyra Dereli[SUP] 1 [/SUP], Seung-Jun Yoo[SUP] 9 [/SUP], Hai Zhou[SUP] 1 [/SUP], Thuc Nguyen Dan Do[SUP] 10 [/SUP], Dirk Jochmans[SUP] 10 [/SUP], Lies Laenen[SUP] 11 [/SUP], Yves Debaveye[SUP] 12 [/SUP], Paul De Munter[SUP] 13 [/SUP], Jan Gunst[SUP] 12 [/SUP], Mark Jorissen[SUP] 14 [/SUP], Katrien Lagrou[SUP] 15 [/SUP], Philippe Meersseman[SUP] 13 [/SUP], Johan Neyts[SUP] 10 [/SUP], Dietmar Rudolf Thal[SUP] 16 [/SUP], Vedat Topsakal[SUP] 8 [/SUP], Christophe Vandenbriele[SUP] 17 [/SUP], Joost Wauters[SUP] 13 [/SUP], Peter Mombaerts[SUP] 18 [/SUP], Laura Van Gerven[SUP] 19 [/SUP]
Affiliations
- PMID: 36446381
- DOI: 10.1016/j.neuron.2022.11.007
Abstract
Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.
Keywords: COVID-19; Coronavirus; Delta; Omicron; RNAscope; SARS-CoV-2; Virchow-Robin space; blood-brain barrier; brain parenchyma; frontal lobe; glia limitans perivascularis; leptomeninges; neuroinvasion; neurotropism; olfactory; olfactory bulb; olfactory sensory neuron; perineurial olfactory nerve fibroblast.