Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence
Open Access
- 31 March 2023
- Vol. 15 (4), 908
- https://doi.org/10.3390/v15040908
Abstract
Background: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic–ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.Keywords
Funding Information
- Austrian Fonds of the Major of Vienna (COVID038)
- Austrian Science Fund FWF, SYNABS (I4685-B)
- the German Academic Exchange Service
- German Academic Scholarship Foundation
- the Goldschmidt-Jacobson Foundation
- National Multiple Sclerosis Society (FG-1708-28871)
- Swiss National Science Foundation (PCEPF3_194609)
- the University of Basel
- the Medical Faculty Mannheim of Heidelberg University
- Hertie Foundation (P1180016)
- European Research Council (DecOmPress” ERC StG)
- German Research Foundation (SCHI 1330/2-1/4-1)
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