Persistent Autonomic and Immunologic Abnormalities in Neurologic Post-Acute Sequelae of SARS-CoV2 Infection, 2024, Goldstein, Walitt, Nath+

Persistent Autonomic and Immunologic Abnormalities in Neurologic Post-Acute Sequelae of SARS-CoV2 Infection
David S. Goldstein, MD, PhD, Yair Mina, MD, Brian Walitt, MD, MPH, Patti Sullivan, CMT, Yoshimi Enose-Akahata, PhD, Steven Jacobson, PhD, My-Le Nguyen, MD, Stanislav Sidenko, BA, RCS, Amanda Wiebold, RN, Bryan Smith, MD, Janna Gelsomino, RN, Risa Isonaka, PhD, Sarah Moore, CRNP, and Avindra Nath, MD

OBJECTIVES
After acute coronavirus disease-2019 (COVID-19), people often experience fatigue, “brain fog,” or other central neurologic symptoms (neuro–post-acute SARS-CoV2, or “NeuroPASC”). In this observational study we evaluated whether abnormalities noted on initial evaluation persist after at least another year.

METHODS
Neuro-PASC research participants who had undergone comprehensive inpatient testing at the NIH Clinical Center returned after at least 1 year for follow-up assessments including symptoms rating scales, MRI, lumbar puncture for tests of the CSF, physiologic recordings during the Valsalva maneuver and head-up tilting (with serial plasma catechols and cardiac Doppler ultrasound during the tilting), blood volume measurement, skin biopsies to examine sympathetic innervation, and blood sampling for neuroendocrine and immunologic measures.

RESULTS
7 patients with Neuro-PASC (6 women, age range 42–63 years) underwent follow-up testing. 71% of initially abnormal test results remained abnormal at follow-up, including the pattern of CSF and serum oligoclonal bands, CSF indices of central catecholamine deficiency, baroreflexcardiovagal dysfunction, the occurrence of tilt-evoked sudden hypotension, white matter hyperintensities on MRI, and adaptive responses in CSF.

DISCUSSION
In Neuro-PASC most of the autonomic and immunologic abnormalities found initially are still present after more than a year.

Link | PDF (Neurology) [Open Access]

 

Hutan beat me to it, but yes, no need for the big breath I and no doubt she took when opening! No evidence of low blood volume sounds useful info (small numbers).

 

Seems like a rag-bag of tests on a small number of people with presumably no information on what those tests showed before Covid or whether their occurrence was due to Covid or coincidence. Since we do not have any clear evidence of relation of Covid to any specific neurological abnormality, other than loss of smell and residues from strokes, it all seems a bit hard to interpret.

It seems more as if these 'neurologic post-acute sequelae' are more along the lines of ME/CFS type symptoms (OI etc). If there were 100 subjects with the same sort of abnormality that would be interesting. Otherwise this sort of 'deep-dive' study of a handful seems pretty pointless.

 

One of the possibly more interesting findings in the intramural study, were the catecholamine findings. They don't report differences in norepinephrine here, but quote the intramural study findings with

It seems valuable that they report

More stability and follow-ups within LC studies will certainly be helpful to separate the more acute from the post-acute phenomena from the normal noise. But at such a small sample size it seems rather useless. I don't think we really need more of these studies.

Could be interesting to have a look at some of the actual data, but I'm certain they will have already compared it to the intramural study data.

It does seem like they report no elevated incidence of markers of neurological injury, like GFAP or NFL, which many other studies have reported which, depending on depending on patient selection, might be a valuable null result (but sample size might have been to small to detect anything in the first place?).

 

Patient sample is the remainder of 12 patients in the initial study:

Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection

https://www.neurology.org/doi/10.1212/NXI.0000000000200097

Clinical Characteristics
"Between October 2020 and March 2021, 12 participants were recruited from a cohort of 173 individuals (see Figure 1A for flowchart of inclusion in the study). Demographics and clinical characteristics of these patients are detailed in Table 1. Participants were all White and mostly female (83%), with a mean age of 45 ± 11 years. The majority of participants had a history of depression/anxiety before COVID-19 (n = 7, 58%). A third of the patients (n = 4) had a prior history of resolved long-term disability after an infectious disease (infectious mononucleosis, Lyme disease, amoebiasis due to Entamoeba histolytica, and severe sepsis due to group A Streptococcus)."

Didn't read the articles nor checked the first study on how they selected the participants from the larger cohort and whether investigators did cognitive testing to have some objective symptom correlates or looked for an ME/CFS subgroup, but thought that sample looks a bit 'special'?

As others said, sample size too small anyway, but in addition I thought it's disappointing that at least in the follow-up study from skimming it seems they weren't interested in PEM, cognitive tests and objective measures on activity / movement patterns (no use of activity trackers or accelerometers)

 

What on earth is the point of these miniscule cohorts? I know its not the kind of study where you'd want hundreds of patients but 7? It makes the ME intramural study look jam packed.

 

I think it’s better than nothing. If something is really out of whack, it will show up even in a small sample.

 

True. But it's the NIH not some tiny funding starved researcher in an obscure university. Why couldn't they have studied more patients?