Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice.
Enric VidalCarlos López-FigueroaJordi RodonMónica PérezMarco BrustolinGuillermo CanteroVíctor GuallarNuria Izquierdo-UserosJorge CarrilloJulià BlancoBonaventura ClotetJúlia Vergara-AlertJoaquim SegalésPublished in: Veterinary pathology (2021)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- cerebral ischemia
- resting state
- white matter
- functional connectivity
- mouse model
- wild type
- type diabetes
- subarachnoid hemorrhage
- spinal cord
- traumatic brain injury
- metabolic syndrome
- pulmonary embolism
- liver failure
- brain injury
- oxidative stress
- hepatitis b virus
- blood brain barrier
- spinal cord injury
- adipose tissue
- copy number
- drug induced
- quantum dots
- lipopolysaccharide induced
- skeletal muscle
- high intensity
- high throughput
- hiv infected patients
- single cell
- loop mediated isothermal amplification