SARS-CoV-2 may cause early delirium in older adults with dementia. To better understand its pathogenesis, we describe cases of Covid-19 in older adults and in one young adult for comparison. We aim to report the clinico-pathological features, particularly the characteristics of microglial activation and the presence of SARS-CoV-2 and lymphocytes in the brain.
Ten brains from subjects with laboratory-confirmed Covid-19 were collected for forensic and diagnostic purposes. Based on the clinical findings and possible topographic distribution of ACE2-receptors in the brain, the sub-ependymal, anterior fronto-temporal, hippocampus, thalamus, and brainstem areas were analysed. Haematoxylin-Eosin and Luxol Fast Blue were used for standard histology. For immunohistochemistry, antibodies against CD68, CD3, CD20, CD34 and SARS-CoV-2 were used. Microglial nodules were graded semi-quantitatively: 0-3 (none-mild-moderate-severe).
The first five cases are described. Clinical findings: 3 patients with dementia (mean:85y/o; 2 females-1 male) had early delirium (2 hyperactive, 1 hypoactive) with sudden changes in behaviour or alertness; 1 patient (67y/o male) had peripheral tetraparesis; the fifth was asymptomatic (29y/o male; prodromal Covid-19, accidental death). Neuropathological findings: all had diffuse cortical oedema, neuronal loss, perivascular inflammatory infiltrates and non-specific microglial activation. Four brains showed moderate-severe microglial nodules (score:2-3) predominantly in the hippocampus and brainstem. Scarce SARS-CoV-2 immunoreactivity and few lymphocytes were detected only in 2 cases.
Microglial nodules in limbic structures and brainstem are probably related to disturbances in behaviour and alertness, respectively. Delirium appears to be caused by a strong and early microglial response, rather than direct viral invasion of the brain.