Prevalence and severity of neurologic symptoms in Long-COVID, pre-existing conditions, hospitalization, mental health, 2025, Huff, Nath, Walitt +

[Hutan]

Hanalise Huff, Henry Roberts, Elizabeth Bartrum, Gina Norato, Nicholas Grayson, Katherine Fleig, Miciah Wilkerson, Barbara Stussman, Avindra Nath, Brian Walitt*

Background: Long-COVID refers to ongoing, relapsing, or new symptoms present 30 or more days after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study examined the prevalence and severity of neurologic symptoms at greater than 1 month following acute SARS-CoV-2 infection and the influence of pre-existing neurologic and psychiatric conditions, current depression and anxiety status, and hospitalization on the presence and severity of these symptoms.

Methods: This prospective cohort study recruited primarily self-referred Long-COVID participants with confirmed SARS-CoV-2 infection. Online questionnaires inquiring about pre-existing conditions, neurologic symptoms and their severity pre, during and post COVID-19, and current anxiety and depression screening were completed by 213 participants at a median time of 8 months after infection. Descriptive analyses and prevalence modeling were performed.

Results: The most frequent neurologic symptoms post COVID-19 were fatigue, concentration/memory difficulties, unrefreshed sleep, and dysarthria/word finding difficulties (73.2-86.4%). Neurologic symptoms were highly prevalent with significantly greater odds post COVID-19 compared to pre for all symptoms and higher prevalence at time periods farther from infection, including those implicit in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Several severe neurologic symptoms were significantly more prevalent post COVID-19. Moderate to severe anxiety (34%) and depression (27%) were observed post COVID-19.

Preexisting neurologic or psychiatric conditions did not demonstrate any significant difference in neurologic symptom prevalence post COVID-19. Those who met criteria for moderate or severe anxiety post COVID-19 had a significant difference in prevalence of fatigue, sensitivity to touch and unrefreshed sleep. Similarly, fatigue, concentration/memory difficulty and unrefreshed sleep were more prevalent in moderate to severe depression. There were no significant differences in neurologic symptom prevalence in a hospitalized group when compared to non-hospitalized.

Long-COVID has a high burden of long lasting and severe neurological sequelae. These sequelae are independent of pre-existing self-reported neurologic and psychiatric conditions, as well as previous hospitalization. Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19. Focus on the biological impact of SARS-CoV-2 on the nervous system will be essential in ameliorating the tremendous symptom burden left in the wake of the COVID-19 pandemic.


Frontiers in Neurology
Link https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1562084/abstract

 

[Hutan]

Moderate to severe anxiety (34%) and depression (27%) were observed post COVID-19.

These levels of anxiety and depression are not unusual in general populations.

The most frequent neurologic symptoms post COVID-19 were fatigue, concentration/memory difficulties, unrefreshed sleep, and dysarthria/word finding difficulties (73.2-86.4%). Neurologic symptoms were highly prevalent with significantly greater odds post COVID-19 compared to pre for all symptoms and higher prevalence at time periods farther from infection, including those implicit in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.

These symptoms are sounding very much like ME/CFS.

There were no significant differences in neurologic symptom prevalence in a hospitalized group when compared to non-hospitalized.

It doesn't look as though severity of the acute illness has much to do with the onset of ME/CFS-like symptoms - although there could be all sorts of things going on with recruitment bias.

Long-COVID has a high burden of long lasting and severe neurological sequelae. These sequelae are independent of pre-existing self-reported neurologic and psychiatric conditions, as well as previous hospitalization.

It will be interesting to see what is behind the statement of Long covid symptoms being independent of pre-existing self-reported psychiatric conditions. The participants appear to all be "primarily self-referred Long-COVID participants with confirmed SARS-CoV-2 infection", and most of them appear to have similar symptoms of fatigue and other ME/CFS-type symptoms. So, I'm not sure what they used to compare the incidence of psychiatric conditions in non-Long Covid patients.

Focus on the biological impact of SARS-CoV-2 on the nervous system will be essential in ameliorating the tremendous symptom burden left in the wake of the COVID-19 pandemic.

Nevertheless, it's good to see this, especially in a paper with Walitt's name on. It is a bit vague though, and arguably puts a bit too much emphasis on the specific pathogen making the impact (as opposed to the body's response to the infection). And, it seems to suggest that the Covid-19 pandemic has passed us now.

Those who met criteria for moderate or severe anxiety post COVID-19 had a significant difference in prevalence of fatigue, sensitivity to touch and unrefreshed sleep. Similarly, fatigue, concentration/memory difficulty and unrefreshed sleep were more prevalent in moderate to severe depression.

Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19.

I'm not sure why it is so hard to understand that if you are experiencing debilitating symptoms including fatigue is one of them, your odds of being found to have anxiety and depression are higher, due to the measurement tools and just because it's difficult and worrying. 'Fatigue, cognition and sleep can impact anxiety and depression status' is at least as true as 'Anxiety and depression status can impact fatigue, cognition and sleep'. Dr Walitt needs a motivational poster on his wall "Correlation is not causation".

 

[Trish]

Given that the whole thing appears from the abstract to have been done via online recruitment and questionnaires, there are all sorts of confounding factors that should make them more cautious about writing an abstract that draws conclusions, especially, as Hutan says, about direction of causation. I don't have the energy to explore further, but if anyone wants to look into the questionnaires used, it wouldn't surprise me if the so called associations are due to overlaps in questions.

 

[Yann04]

Haven’t we done this same retrospective study with heavy selection biases like 30+ times.

Perhaps instead pool the money together and fund a well done pre-illness prospective study?

(The abstract calls it prospective but they seem to mention they only recruited after Long COVID started so that doesn’t make sense to me?)

This prospective cohort study recruited primarily self-referred Long-COVID participants

Like isn’t that an oxymoron??

 

[MSEsperanza]

(The abstract calls it prospective but they seem to mention they only recruited after Long COVID started so that doesn’t make sense to me?)
Like isn’t that an oxymoron??

From another thread:

About the terms ‘prospective' and ‘retrospective' in observational studies in epidemiology.

Not up to word my question so just leave this quote from the STROBE Initiative here.

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE):

"We recommend that authors refrain from simply calling a study ‘prospective' or ‘retrospective' because these terms are ill defined [29].

"One usage sees cohort and prospective as synonymous and reserves the word retrospective for case-control studies [30].

"A second usage distinguishes prospective and retrospective cohort studies according to the timing of data collection relative to when the idea for the study was developed [31].

" A third usage distinguishes prospective and retrospective case-control studies depending on whether the data about the exposure of interest existed when cases were selected [32].

"Some advise against using these terms [33], or adopting the alternatives ‘concurrent' and ‘historical' for describing cohort studies [34].

" In STROBE, we do not use the words prospective and retrospective, nor alternatives such as concurrent and historical. We recommend that, whenever authors use these words, they define what they mean. Most importantly, we recommend that authors describe exactly how and when data collection took place."

Source:
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. 2007 Oct 16;4(10):e297. doi: 10.1371/journal.pmed.0040297.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020495/

 

[rvallee]

Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19

No, it does not. It can be framed this way, when using bad questionnaires, because they ask overlapping questions. The main problem here being that medicine routinely asks overlapping questions without caring how it makes the results uninterpretable. Which they interpret anyway!

Why are they still wasting time on trivial nonsense like this? It doesn't matter one way or another, we have known this is not relevant for years. That they found that it's not significant is just as irrelevant, those who have made up their minds won't care one way or another. It's not even a high quality study, it has all the flaws that every smaller study has.

I'm still wondering if I missed things, but what the hell is the NIH doing with their RECOVER thing? There hasn't been a single major study published so far. It's all trifling nonsense and small studies, like this one, which is just a copy of dozens of identically worthless studies done before. Their giant $1.15B budget... where the hell is it?!

Damn is what's happening right now at the NIH ugly, but it's hard to argue that medical research doesn't need a giant kick in the face for being so wasteful and foolish when they're not directly working on biology using advanced technology. The rest is overwhelmingly mediocre.

 

[V.R.T.]

No, it does not. It can be framed this way, when using bad questionnaires, because they ask overlapping questions. The main problem here being that medicine routinely asks overlapping questions without caring how it makes the results uninterpretable. Which they interpret anyway!

Why are they still wasting time on trivial nonsense like this? It doesn't matter one way or another, we have known this is not relevant for years. That they found that it's not significant is just as irrelevant, those who have made up their minds won't care one way or another. It's not even a high quality study, it has all the flaws that every smaller study has.

I'm still wondering if I missed things, but what the hell is the NIH doing with their RECOVER thing? There hasn't been a single major study published so far. It's all trifling nonsense and small studies, like this one, which is just a copy of dozens of identically worthless studies done before. Their giant $1.15B budget... where the hell is it?!

Damn is what's happening right now at the NIH ugly, but it's hard to argue that medical research doesn't need a giant kick in the face for being so wasteful and foolish when they're not directly working on biology using advanced technology. The rest is overwhelmingly mediocre.

It's baffling. As JE said recently, why didn't they fund a GWAS? Instead we've got this monstrous lumbering buereucratic apparatus that almost seems designed not to find the answers and to waste as much money as possible. I believe they have a lot of different types of samples collected from thousands of patients, maybe they will prove useful when DecodeME gives us more clues.

I did think recently that if there were a finding that showed where to look clearly then perhaps RECOVER might be able to pivot to research and clinical trials around whatever the breakthrough is and then suddenly it would be valuble. Although given the current shitshow I don't have much hope.

 

[Yann04]

It’s quite baffling that I have like 5 times more hoped stacked in a team from Edinburgh than a 1.65 billion initiative by the largest health research funder.

 

[V.R.T.]

I did think recently that if there were a finding that showed where to look clearly then perhaps RECOVER might be able to pivot to research and clinical trials around whatever the breakthrough is and then suddenly it would be valuble.

I believe what I was actually thinking was maybe the RECOVER TLC trials could take pointers from DecodeME and LOCOME. And that way have much more chance of a successful trial.

But let's be honest its may well end up being more paxlovid and brain training.

 

[V.R.T.]

It’s quite baffling that I have like 5 times more hoped stacked in a team from Edinburgh than a 1.65 billion initiative by the largest health research funder.

I remember how much hope I felt for RECOVER at first. It was announced at precicely the same time I became severe. Watching it flounder and bake in failure from the start was soul crushing.