[Preprint] COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei, 2022, Emmi et al

COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Aron Emmi, Stefania Rizzo, Luisa Barzon, Michele Sandre, Elisa Carturan, Alessandro Sinigaglia, Silvia Riccetti, Mila della Barbera, Rafael Boscolo-Berto, Patrizia Cocco, Veronica Macchi, Angelo Antonini, Monica De Gaspari, Cristina Basso, Raffaele De Caro, Andrea Porzionato

Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it’s still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms.

Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.

BioRxiv | PDF (preprint)

 

Postmortem study during the Italian first wave. Matched controls (mostly pre-pandemic, and/or deemed Covid-19 neg). Cases and controls died of pneumonia / respiratory failure.

Highlighted limitation (presume they mean pre-hospitalisation neurological status):

 

Some quotes that stood out to me —

Additionally —

 

And, of course, this paragraph represents "a bit of a worry" for the long, long tail of long Covid (cf post-polio syndrome) —

 

I have long wondered if ME could be triggered not so much by certain pathogens but by pathogens getting into critical areas, one of which is the brain. It could be strongly symptomatic (encephalitis, meningitis etc.) or largely asymptomatic, but the immune system might enact emergency measures it does not normally do. The latest hypothesis that fits this, still unproven, is the Itaconate shunt hypothesis.

So a virus in heart, brain or eyes, the latter two being immune privileged areas, could trigger a deep antipathogen response.

I also like that the Itaconate shunt is looking at innate immunity, not acquired immunity. We do not look at that nearly enough in my opinion. I have long wondered what innate immune responses occur to the higher quantities of lipopolysaccharides sometimes found in ME patient blood.

Viral presence in the brain would be exactly this kind of thing. Not nearly enough for proof of course, but a start.

 

Interestingly, although immunosuppression is required for cardiac transplants, heart valves are immune privileged, although that doesn't prevent rheumatic heart disease of course.