Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

Zane Jaunmuktane^{1

2}, Ula Mahadeva³, Anna Green³, Vivek Sekhawat³, Nicholas A Barrett^{4

5}, Lucy Childs⁶, Manu Shankar-Hari^{4

7}, Maria Thom^{8

9}, Hans Rolf Jäger^{10

11}, Sebastian Brandner^{12

13}

Affiliations

¹ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK. z.jaunmuktane@ucl.ac.uk.
² Department of Clinical and Movement Neurosciences and Queen Square Brain Bank for Neurological Disorders, Queen Square Institute of Neurology, University College London, London, UK. z.jaunmuktane@ucl.ac.uk.
³ Department of Cellular Pathology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁴ Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁵ Faculty of Life Sciences and Medicine, King's College London, London, UK.
⁶ Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷ School of Immunology and Microbial Sciences, King's College London, London, UK.
⁸ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
⁹ Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
¹¹ Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, Queen Square Institute of Neurology, University College London, London, UK.
¹² Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK. s.brandner@ucl.ac.uk.
¹³ Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK. s.brandner@ucl.ac.uk.

PMID: 32638079
PMCID: PMC7340758
DOI: 10.1007/s00401-020-02190-2

Case Reports

Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

Zane Jaunmuktane et al. Acta Neuropathol. 2020 Sep.

. 2020 Sep;140(3):397-400.

doi: 10.1007/s00401-020-02190-2. Epub 2020 Jul 8.

Authors

Affiliations

¹ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK. z.jaunmuktane@ucl.ac.uk.
² Department of Clinical and Movement Neurosciences and Queen Square Brain Bank for Neurological Disorders, Queen Square Institute of Neurology, University College London, London, UK. z.jaunmuktane@ucl.ac.uk.
³ Department of Cellular Pathology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁴ Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁵ Faculty of Life Sciences and Medicine, King's College London, London, UK.
⁶ Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷ School of Immunology and Microbial Sciences, King's College London, London, UK.
⁸ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
⁹ Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
¹¹ Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, Queen Square Institute of Neurology, University College London, London, UK.
¹² Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK. s.brandner@ucl.ac.uk.
¹³ Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK. s.brandner@ucl.ac.uk.

PMID: 32638079
PMCID: PMC7340758
DOI: 10.1007/s00401-020-02190-2

No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Fig. 1**
Case 1: a, b Head-CT shows recent (blue arrows) and established (white arrows) multifocal infarcts. c Rusty discolouration (red arrows) on brain surface. d Right uncal grooving (red arrow). e Bilateral acute and subacute watershed infarcts in the anterior-MCA and MCA–PCA territories and a subacute infarct in the right lentiform nucleus (red arrow). **f, g** Dense inner rim of degenerating neutrophils (blue arrow) and h, an outer rim (blue arrow) of macrophages (CD68). **i, j** Macroscopy and microscopy of confluent infarcts across the right MCA territory (acute and subacute, red arrow). k Infarcts are ischaemic, with granulation tissue and macrophages (blue arrow), or l, with perivascular haemorrhages and fibrin thrombi (blue arrow). m Bilateral acute and subacute infarcts in the PCA territories (both occipital lobes (red arrow), and i left hippocampus and thalamus. **n, o** Frequently, subacute infarcts show prominent leukocytoclastic reaction (blue arrow). p Multiple subacute cortical infarcts in both cerebellar hemispheres (red arrows)

**Fig. 2**
Case 2: a MRI brain (FLAIR image) shows leukoaraiosis and high signal intensity in the right (red arrow) but not left (white arrow) intraparietal sulcus. b Microhaemorrhage on the left (red arrow), but no gross leptomeningeal pathology. **c, d** Histology shows mild leptomeningeal lymphohistiocytic inflammation in the right (d), but not left (c) intraparietal sulcus. e Arrows point to microhaemorrhages (T2*weighted MRI), f macroscopically (red arrows) and **g, h** microscopically corresponding to acute and subacute white matter microbleeds. i Small acute infarcts (DWI MRI, black arrows), j macroscopically corresponding to white matter lesions (ø1-4 mm, red arrows). k Histologically, some are classic acute and subacute microinfarcts (red arrow), l whilst others contain haemosiderin-laden macrophages, m shown with Perls staining. n CD68 accentuates many more lesions than evident macroscopically or on MRI. o Unremarkable blood vessels are seen within some of the white matter microlesions (CD34 immunostaining). p Swollen axons (indicating damage) on neurofilament (SMI31) immunostaining q but no demyelination (myelin basic protein (SMI94) immunostaining). r Macroscopic and microscopic examination (inset in r shows macrophage-rich necrosis) reveal bilateral subacute pallidal infarcts. s Occasional subacute microinfarcts in the cortex (ø1–5 mm), some with haemorrhagic transformation (inset in s). t High MRI T1 signal foci (white arrow) in the cerebellum correspond histologically to u subacute infarct, v fresh leptomeningeal haemorrhages and (not shown) non-haemorrhagic white matter microlesions. w Several chronic infarcts and microinfarcts (likely embolic) in cerebellar cortex and right thalamus (not shown)

See this image and copyright information in PMC

References

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Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

Affiliations

Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

Authors

Affiliations

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources