Brainstem damage in COVID-19

ABSTRACT

Background and aims: It has recently been proposed that SARS-CoV-2 might spread through the nervous system in a prion-like way, reaching respiratory centers in the brainstem. Here, we evaluated neuropathologically, neurophysiologically and clinically the brainstem involvement in COVID-19. Methods: Neuropathological data were acquired from patients died for COVID-19 and COVID-19 negative;neuronal damage and the number of corpora amylacea (CA)/mm2 were assessed. The expression of the nuclear proteinof SARS-Cov-2 was also evaluated. To clarify whether neuropathological findings had a functional correlate, we studied the blink reflex (BR) in 11 COVID-19 patients, admitted to our Intensive Care Unit (ICU), and compared data both with healthy subjects and non COVID- 19 ICU patients. An extensive neurological examination, comprising the corneal and glabellar reflexes, was also performed. Results: Autopsies showed a high percentage of neuronal damage and a higher number of CA in the medulla oblongata of COVID-19 patients;immunohistochemistry revealed the presence of SARS-Cov-2 virus in the brainstem. Neurophysiologically, the RII component of the BR was selectively impaired in COVID-19 and, clinically, the glabellar reflex reduced or absent. Conclusion: Our findings provide the first combined neuropathological, neurophysiological and clinical evidence of SARS-Cov-2-related brainstem involvement, especially at the medullary level, suggesting a neurogenic component of respiratory failure.