Neurodivergence as a risk factor for Post-Covid-19 Syndrome, 2023, Raw et al

[Dolphin]

https://www.medrxiv.org/content/10.1101/2023.06.08.23291154v1

Neurodivergence as a risk factor for Post-Covid-19 Syndrome
Rachael K. Raw, Jon Rees, Amy Pearson, David R. Chadwick
doi: https://doi.org/10.1101/2023.06.08.23291154
This article is a preprint and has not been peer-reviewed

Abstract

Neurodivergent (ND) individuals (e.g., Autistic people) are more likely to experience health problems that are characterised by central sensitisation ’.

Recent research suggests that a so-called ‘Long-COVID’ syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Using a standardised assessment tool, we examined whether traits associated with Autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCW)..

Higher autistic traits predicted COVID-19 symptoms that lasting more than 12 weeks regardless of formal autism diagnosis.

A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4-12 weeks, though the direction of causality in this case is uncertain.

Limitations of the present study are
1) the retrospective nature of COVID-19 symptom reporting;
2) likely self-selection bias given the high number of HCWs who reported long-term COVID-19 symptoms;
and
3) the gender-bias towards females in our sample.

Funding Statement
The CHOIS study was supported by the North East and North Cumbria Academic Health Sciences Network (AHSN; fund awarded to co-author DRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Key Words: SARS-CoV-2; COVID-19; Long-COVID; Post-Covid-10 Syndrome; 15 Chronic Fatigue Syndrome; Autism; Neurodivergence; Neurotypical

 

[Hutan]

The lead author comes from Newcastle-upon-tyne - people from the Me/CFS clinic there made an horrendous submission to the NICE guideline process.

First paragraph of the abstract:

Neurodivergent (ND) individuals (e.g., Autistic people) are more likely to experience health problems that are characterised by central sensitisation'. Recent research suggests that a so-called ‘Long-COVID’ syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

I don't know about central sensitisation in neurodivergent people ('neurodivergence' surely covers a lot of different things?), but it's far from proven that ME/CFS is explained by a 'heightened response to internal physiological stimuli'.

Later in the text it is said that the mechanisms underlying ME/CFS are not fully understood, and that Central Sensitisation is only a 'key theory'. But then later in the paper, the certainty is back:

Conditions characterised by CS, such as ME/CFS, are more common in those with ASD[11].

It was an online survey, so, for sure, self-selection is likely to have been an issue.

HCWs were invited to self-declare whether they were neurodivergent. Autistic traits were assessed using the Ritvo Autism & Asperger Diagnostic Scale (RAADS-14)

124 (46%) resolved within 4wks (AC), 64 (24%) between 4-12wks (OCS) and 79 (30%) had symptoms >12wks (PCS).

There was no significant association between either OCS or PCS and self-declared ND status ( 2(2)=2.59, p=.27). Based on the RAADS cut-off of 14, 83 (31%) scored above this threshold and there was a significant association of being above threshold with likelihood of experiencing OCS or PCS( 2(2)=10.01,p=.007).

So, there was no significant association between being (self-declared) neurodivergent and having persisting systems.

 

[Hutan]

Examining the subscales of the RAADS, there was no difference between COVID-19 duration groups on mentalising (F(2,259)=2.37, p=.10) or social anxiety (F(2,259)=2.5, p=0.08), but a significant difference in sensory reactivity (F(2,259)=4.85, p=.009), with post- hoc testing showing that there was a significant difference between the AC and PCS (1.62 (2.49) vs 3.81 (3.02)). There was no overall difference in DS14 between the COVID-19 duration groups (F(2,259)=2.41, p=.09). Negative affectivity was significantly higher in those experiencing OCS (F(2,272)=3.72, p=.03), but not those with PCS. See Table 1 for HCW characteristics.

Mentalising (the ability to think about thinking?) - no effect on risk of persisting symptoms
Social anxiety - no effect on risk of persisting symptoms
Sensory reactivity - significant risk

DS14 is a measure of negativity and social inhibition - no overall effect on risk of persisting symptoms
Negative affectivity was only higher in people in the 4-12 week period; surprisingly, it wasn't significant in people still with symptoms after 12 weeks.

 

[Hutan]

In our sample 30% described having COVID-19 symptoms beyond 12wks post-infection. This is alarmingly high, given the extent to which ongoing COVID-19 symptoms can impact daily life.

I didn't see a clear description of how they asked about persisting symptoms. I didn't see it noted that respondents were required to only note symptoms that were significantly worse after the infection than before. And then there's also the self-selection issue - people are way more likely to answer a survey about persisting symptoms if they have them, than if they don't and would rather not think about the risk of getting them.

Regarding Type D Personality, TDP traits overall were not different across the AC/OCS/PCS groups. Importantly, the confounder of negative affect was only marginally associated with OCS, and not at all with PCS. The direction of causality in this finding must be carefully considered, as it is unclear as to whether the presence of OCS might have led to greater negative affect, or if those with naturally greater negative affectivity were more likely to have had symptoms for longer because they perhaps did not take the actions necessary to accelerate their recovery (e.g., returning to regular activities).

While it's great that the authors were able to consider that an association doesn't tell us about the direction of causality, the prejudice embedded in that discussion is pretty horrible, and a bit illogical.
In their view, people with persisting symptoms from 4 to 12 weeks, who were statistically more likely to be showing negative affect, might be experiencing those symptoms because they didn't "take the actions necessary to accelerate their recovery" (e.g. returning to regular activities). And yet, the people still stuck with persisting symptoms after 12 weeks didn't tend to show negative affect...

Interestingly only 13% of HCW self-declared that they were neurodivergent, whereas 31% of the group scored above threshold on the RAADS. This is consistent with evidence to suggest that people with fewer stereotypical characteristics frequently go un-diagnosed[16]. Analyses also revealed that PCS was predicted by the 'sensory reactivity' subscale of the RAADS, suggesting that HCWs who scored highly on this element were more likely to have prolonged symptoms. This finding fits with the theory that a CS mechanism may underlie conditions such as ME/CFS[9].

It looks as though this 'sensory reactivity' is the only real finding related to personality or behaviour in this paper. This is a sub scale of the RAADS-14 instrument. The whole instrument has only 14 questions. The questions possibly relating to 'sensory reactivity' are:
2. Some ordinary textures that do not bother others feel very offensive when they touch my skin.
7. When I feel overwhelmed by my senses, I have to isolate myself to shut them down.
10. Sometimes I have to cover my ears to block out painful noises (like vacuum cleaners or people talking too much or too loudly)

The possible responses are:

• true now and when young
• true only now
• true when I was young
• never true

The paper does not tell us if the respondents on this survey were given the options around when the sensitivities occurred. It is entirely possible that the correlation between persisting symptoms and the 'sensory reactivity' subscale of the RAADS-14 is because people with persisting symptoms are experiencing noise sensitivity that they did not previously and are taking to their bed when they have PEM.

Our key findings are first, more HCWs scored above threshold for neurodivergence than those who self-declared having been diagnosed neurodivergent

They only assessed using a scale for autism. They can't then make a claim about a wider neurodivergence category.



This is a mediocre paper. It does not explain its methodology clearly enough, it states things as facts that are not known (e.g. that central sensitisation explains ME/CFS), and reeks of prejudice against people who are experiencing persisting symptoms (e.g. that they have not tried to return to normal activities).

 

[RedFox]

Wouldn't be surprised at all if autism is a risk factor for long Covid. There's extensive research on immune differences in autism, for example, "Immunity-linked genes expressed differently in brains of autistic people," and parents with autoimmune disease are a bit more likely to have an autistic child.

However, answers on a questionnaire are a terrible proxy for autism. Also, the researchers found no correlation between actual autism/ADHD/etc. I smelled a rat when I saw that, though the number of neurodivergent people is probably too low (16) to be meaningful. They found no correlation with mentalizing or social anxiety. They did find correlations with sensory sensitivity and low mood (the latter only in those sick less than 12 weeks). Um, we know LC causes sensory sensitivity and being sick can affect your mood.

Then the authors reverse the likely direction of causality so they can be ableist, which is disgusting.

 

[Simbindi]

However, answers on a questionnaire are a terrible proxy for autism

Agreed. Questionnaires are on1y a part of a fu11 autism assessment. Many of the questions on them don't even make sense to an autistic person, they're not even 1ogica1. For examp1e, I don't fee1 'offended' by various textures touching my skin, I fee1 pain! If I have to have continuous contact with materia1s that effect me I deve1op a rash or hives (often within minutes) that can take weeks to hea1. Definite1y not a 'persona1ity trait'.

 

[Simbindi]

What I have found is that the severity of my ME a1ong with natura1 aging has had a profound impact on my abi1ity to manage my autism. I can no 1onger use any of my 'work arounds' or 'masking adaptations'. So my autism makes dai1y 1iving and socia1 interaction much more difficu1t the more severe my ME has become (1ong term trajectory).

Most autistic peop1e I know get fatigued very easi1y. So even the otherwise young, fit and hea1thy ones require regu1ar naps throughout the day and 1ots of s1eep over a 24 hour period (a1though not necessari1y at night, many have s1eep reversa1 prob1ems 1ike in ME). So I can see having Covid, with the post vira1 consequences it brings, wi11 1ike1y impact autistic peop1e's (and other neurodivergent individua1s) dai1y 1iving significant1y just because they wi11 not be ab1e to use acquired coping techniques when i11.