SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques

Abstract

SARS-CoV-2 may cause acute respiratory disease, but the infection can also initiate neurological symptoms. Here we show that SARS-CoV-2 infection causes brain inflammation in the macaque model. An increased metabolic activity in the pituitary gland of two macaques was observed by longitudinal positron emission tomography-computed tomography (PET-CT). Post-mortem analysis demonstrated infiltration of T-cells and activated microglia in the brain, and viral RNA was detected in brain tissues from one animal. We observed Lewy bodies in brains of all rhesus macaques. These data emphasize the virus' capability to induce neuropathology in this nonhuman primate model for SARS-CoV-2 infection. As in humans Lewy body formation is an indication for the development of Parkinson's disease, this data represents a warning for potential long-term neurological effects after SARS-CoV-2 infection.

The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models

“…The first three studies did not find evidence of the virus in the brain using PCR at 3, 4, 7, and 21 days after infection [27,70,83] (Table 3). A fourth and fifth study [44,78] found viral RNA in multiple brain regions at 28 or 35 days post infection, but in one of these studies, the PCR findings could not be verified by antibodies against the nuclear capsid antigen [78]. A sixth study [51] found evidence of virus RNA and nuclear capsid antigen in the brain, including the olfactory bulb, at 1, 4 and 7 days after nasal inoculation.…”

Delirium in COVID-19: can we make the unknowns knowns?

“…Similar neurotropic viruses such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS-CoV-1) coronaviruses have been shown to trigger the formation of Lewy bodies which are present in a range of neurologic diseases including Parkinson’s dementia. In a post-mortem analysis of the brains of rhesus macaques infected with SARS-CoV-2 virus, in the midbrain region was infiltrated by T-lymphocytes, activated microglia and intracellular Lewy bodies [ 13 ]. Such observations might herald a higher proportion or severity of critical illness induced long-term cognitive impairment or accelerated dementia (Fig.…”

Long COVID and the brain network of Proust's madeleine: targeting the olfactory pathway

“…Viral trans-synaptic progression has previously been demonstrated with other coronaviruses [13]. Both RNA and protein of the virus have been found in neurons of patients who died from severe SARS-CoV-2 [14] and accompanied T cell infiltration and microglial activation in euthanized macaques after apparent remission of COVID-19 [15]. Such neuroinflammation requires long-term follow-up, considering the known relationships of neuroinflammation with the onset and progression of neurological and psychiatric diseases.…”