CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome, 2022, Mar Guasp et al

Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear.

In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months.

We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other.

Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement.

In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.

https://www.frontiersin.org/article...T&utm_campaign=ECO_FIMMU_XXXXXXXX_auto-dlvrit

 

Isn't that kind of redundant, since cell death is inflammatory? It's not the expected cytokines, sure, but cell death gets the immune system going as well, especially infected cells since their content gets released and along with them many viral particles and proteins. At the very least this would get glial cells very active.

If inflammation is limited to "much cytokines around", what is the name for the process by which there is a lot of inflammation in response to cell death? Also, what's found in a spinal tap isn't necessarily indicative of what is present local to the site of immunological activity. If cells are dying, for sure there's activity going, and there has to be cytokines, they just don't necessarily make it far enough to be found in the CSF lower down the spine.

It's a real bummer we can't just poke around there but sometimes you have to accept that there are technical limits to what can be done on a live person. Medicine so badly needs an equivalent of an uncertainty principle, almost everything they do is with limited information and that this is not a fundamental part of medicine is frustrating to all hell.

 

The wording is naff, I agree, but it is reasonably clear what is meant. Cell death in this context is not in itself inflammatory. It may be due to viral cytotoxicity, although the evidence for that in brain seems limited for Covid. It may very well be ischaemic or embolic - basically stroke. At the levels of pO2 seen in some patients bits of brain can easily die from oxygen lack if vessels are compromised.

A lot of cell death is apoptotic - which more or less by definition does not lead to inflammation, just silent clearance.

So you can see what they are trying to say, but I agree that measuring cytokines in CSF is a fairly dodgy way to exclude inflammation.

 

That's what I was thinking of. With apoptosis you can get neat vesicles that (probably) don't leak out too much stuff and can be gobbled up whole, but if it's because of viral replication bursting out it would explode everything around it. Can this be differentiated?