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. 2022 Jul 5:awac151. doi: 10.1093/brain/awac151

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Published by Oxford University Press on behalf of the Guarantors of Brain 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Microvascular injury and thrombus formation. Immunostaining for (A and B) fibrinogen, (C and D) CD61 for activated platelets, (E and F) vWF and (G and H) PECAM-1 shows absence or minimal staining in the non-COVID-19 brain but in the COVID-19 patients, there was (B) perivascular leakage of fibrinogen, (D) platelet aggregates, (F) thrombi and (H) increased PECAM-1 on endothelial cells. Significantly greater (I) leakage of fibrinogen (**P = 0.0011, ****P < 0.0001) and (J) blood vessels with platelet aggregates were present in the COVID-19 brains (****P < 0.0001). (K) PECAM-1 was significantly increased in the brains of COVID-19 patients compared to non-COVID-19 controls (****P < 0.0001). (L–N) Dots represent the average of individual values in the brain regions that make up the forebrain or hindbrain of a patient. The forebrain includes the cerebrum, basal ganglia and thalamus. The hindbrain contains the pons, medulla and cerebellum. (L) Strong fibrinogen deposition was equally distributed in different regions of the brain, while weak deposition was more prevalent in the hindbrain compared to the forebrain (*P = 0.04). (M) There were more thrombi in the hindbrain compared to the forebrain of the COVID-19 patients (*P = 0.04). (N) PECAM-1 immunostaining was equally distributed in different brain regions of the COVID-19 patients. Data represents mean ± SEM. Scale bars = 100 µm.