Longitudinal analysis and treatment of neuropsychiatric symptoms in post-acute sequelae of COVID-19, 2023, Liu et al

[Hutan]

2023 study
https://link.springer.com/article/10.1007/s00415-023-11885-x
Paywall

Jennifer H. Yang, Lucas Patel, Jasmine Arora, Amanda Gooding, Ronald Ellis & Jennifer S. Graves
San Diego team, University of California

Abstract
Background
Persistent neuropsychiatric symptoms following acute COVID-19 infection are frequently reported. These include anxiety, depression, difficulty concentrating, fatigue, and insomnia. The longitudinal evolution of this neuropsychiatric burden is poorly understood and clinical guidelines concerning treatment are lacking.

Objective
We sought to describe the longitudinal evolution of neuropsychiatric symptoms in the post-acute sequelae of COVID-19 (PASC) syndrome and examine symptom treatment at a single center.

Methods
Consecutive participants experiencing persistent neurologic symptoms after acute COVID-19 infection were recruited from October 2020 to July 2022. Data collected included COVID-19 infection history, neurological exam and review of systems, Montreal Cognitive Assessment (MoCA), and self-reported surveys concerning neuropsychiatric symptoms and treatment. Data were collected at baseline and at 1-year follow-up.

Results
A total of 106 participants (mean age 48.6, females 67%) were included in the study. At 1-year follow-up, 72.5% of participants reported at least one neuropsychiatric symptom. Over half (52.5%) of participants reported persistent fatigue. At baseline, 38.8% of all participants had met the established MoCA cut-off score of < 26 for mild cognitive impairment; this decreased to 20.0% at 1 year. COVID-19 infection severity was associated with neuro-PASC symptoms (including fatigue and anxiety) at 1 year. Overall, 29% of participants started at least one new medication for COVID-19-associated neuropsychiatric symptoms. Of the participants who started new medications, fatigue was the most common indication (44.8%) followed by insomnia (27.6%).

Conclusions
Neuropsychiatric symptoms related to neuro-PASC improve over time but can persist for over a year post-recovery. Most treatment modalities targeted neuro-PASC fatigue.

 

[Hutan]

I posted it because it was cited by another study as suggesting that amantidine (an anti-viral) is the most prescribed medicine for post-Covid-19 fatigue, but the abstract doesn't tell us anything about that.
Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children, 2025, Li et al

In this Liu et al paper there might be some discussion of other medications tried, although the study is a bit old now. Perhaps this team has done later studies.

 

[Nightsong]

Out of 106 total study participants, 100 were evaluated for PASC treatment exposures with six excluded due to lack of electronic medical chart access. We found that out of these 100 participants, 29 individuals (29%) started treatment (medications, supplements, therapy, etc.) for neuropsychiatric symptoms attributable to neuro-PASC (Table 5). Of the 29 individuals who started new treatment, 12 were trialed on more than one medication for a single indication.

Out of the participants who started new medications, fatigue was the most com- mon indication (44.8%) followed by insomnia (27.6%). The most common medication used for fatigue was amantadine (53.8% of prescriptions for fatigue). Overall, there was a large spectrum of medications and supplements used to treat the conditions listed. Generally, there was not a consistent pattern or drug-of-choice for neuro-PASC symptoms.

In our analysis of treatments targeting fatigue, amantadine was the most prescribed medication for fatigue in our patients. Amantadine is a commonly used medication for MS-related fatigue and relatively accessible without controlled substance restrictions. The mechanism underlying fatigue in long COVID is still being evaluated, but it has been hypothesized to be related to an aberrant immune response to the virus and may have similarities to autoimmune CNS diseases [15]

Two different studies seeking to treat Post-Viral or Post-COVID-19 Fatigue Syndrome are taking different approaches, one using Ruconest, a recombinant C1 esterase inhibitor indicated for the treatment of acute angioedema attacks, and the other using low-dose naltrexone (LDN) [18, 19]. Ruconest is a strong inhibitor of the complement system, kallikrein–kinin system, and the contact activation system, and is hypothesized to potentially correct immune dysfunction resulting from COVID-19 infection [20].

LDN has been demonstrated to exhibit immunomodulatory activity involving inhibition of B- and T-lymphocytes, antagonism of opioid growth factor receptor, and modulation of antigen-presenting cells such as microglia and macrophages; use of LDN has been shown to have some benefits in symptom control in conditions including multiple sclerosis and chronic fatigue syndrome [21, 22].

 

[rvallee]

difficulty concentrating, fatigue, and insomnia

None of those issues are psychiatric, and even the depression part mostly comes straight from those. What is this horseshit? They can't even define their thing and they impose it on us like it's words written on stone tablets handed by burning bushes. We deserve so much better than this junk.

 

[Hutan]

Thanks @Nightsong.

So, out of 100 participants evaluated for 'PASC treatment exposures', only 29 started treatment for 'neuropsychiatric symptoms' (which includes fatigue).

It's not clear if, in that second quote in Nightsong's post, 'the participants who started new medications' is the same as the 29, or if it is a bigger group who started treatment for any PASC symptom, not just neuropsychiatric. I suspect they are just talking about the 29, given the title of the paper.

If so, 44.8% of the 29 started their new treatment because of the symptom of fatigue. That's 13 people. Of the 13 people, 53.8% of the prescriptions were for amantidine. That's 7 people. 7 out of 100 people evaluated.

Therefore, I think the suggestion in the Chinese review that cites this paper as saying that amantidine is the most prescribed medicine for PASC fatigue is an example of how something reported in a very small number of people can be exaggerated when it is cited.

And that could be a problem. In the case of Amantadine, this CFS study found that people taking it had a lot of side effects and it didn't help.Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome, 1997, Plioplys et al

 

[Nightsong]

Yeah, n=13 for fatigue, 7 of those with amantadine. Here's the table of treatments for each indication: