乌鸦传媒

People with persistent cognitive changes after mild COVID-19 had elevated levels of immune activation and immunovascular markers in their cerebrospinal fluid (CSF) 10 months after acute SARS-CoV-2 infection, according to a late-breaking abstract presented at the American Academy of Neurology (AAN) annual meeting.

In this exclusive 乌鸦传媒 video, study author , of the University of California San Francisco, takes us through the presentation from the meeting and her hypotheses based on the data.

Following is a transcript of her remarks:

Many millions of people experience persistent cognitive issues after SARS-CoV-2 infection, which can impact even young healthy adults who had a mild case of COVID. However, there are not yet effective laboratory tests or treatments for COVID-associated cognitive changes, in part because we do not understand the underlying biology.

An objective of our study is to determine if there is an inflammatory signature in the cerebrospinal fluid of people with persistent cognitive issues after COVID.

We enrolled participants who had recovered from confirmed mild SARS-CoV-2 infection on a structured 2-hour neurocognitive interview. They had to either endure new and persistent cognitive symptoms or have no cognitive symptoms after COVID. All participants were offered optional lumbar puncture and over 50% consented.

So, in this group of 13 participants with cognitive issues and five controls with no cognitive symptoms after COVID, the median age was 40 years old and the cerebrospinal fluids collected a median of 10 months after the first COVID symptoms.

Those with persistent cognitive issues had higher levels of two cerebrospinal fluid immunovascular markers, C-reactive protein and CSF serum amyloid A. We similarly found trends in higher values for several CSF immune activation markers: IP-10, interleukin-8, and an immunovascular marker, the soluble receptor for the vascular endothelial growth factors.

We previously reported that over 40% of affected individuals had a delayed onset of these cognitive symptoms, meaning the person had COVID and only 1 or more months later, the cognitive symptoms began. We wanted to know if this timing of onset was associated with biological distinctions.

We found that having cognitive changes within the first month after COVID was associated with higher levels of a CSF immunovascular marker, VEGF-C, compared to those with delayed-onset cognitive symptoms, as well as the cognitive control group. Those with early-onset cognitive symptoms also had higher CSF levels for several immune activation immunovascular markers -- IP-10, IL-8, placental growth factor, and ICAM-1 -- compared to the cognitive controls.

Well, this is a very small study. Our hypothesis based on our data is really that we know that endothelium in the vasculature has been shown to be responsive to inflammation and SARS-CoV-2 infection. And that this can shift the cells away from their usual homeostatic functions towards persistent immune cell infiltration and angiogenesis and repair.

And, so, what our data suggest is that perhaps in these people with more acute-onset cognitive changes, that they really don't have the return of homeostasis of the vasculature, that they don't go back to their normal functions. And that for some reason, there's this persistent activation. And that the people with more delayed-onset cognitive changes, that we're really seeing that they look very similar to people who had COVID, who aren't experiencing cognitive issues, suggesting that perhaps it's something with autoantibodies or some other process that could be involved.

So, perhaps these individuals had higher viral loads to begin with, perhaps there was kind of more challenge to the body and the vasculature to begin with, that dictated some of these changes. Or, perhaps there's some host factors or host immunologic factors that kind of led to these changes.

So, again, I think it's a little bit hard to speculate knowing that we have such preliminary data, but I think that we're really looking forward to seeing how these data bear out in larger sample sizes to really test out these hypotheses more.

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