Preprint Wearable heart rate variability monitoring identifies autonomic dysfunction and thresholds for post-exertional malaise in Long COVID, 2025, Ruijgt+

forestglip

forestglip

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Wearable heart rate variability monitoring identifies autonomic dysfunction and thresholds for post-exertional malaise in Long COVID

Twan Ruijgt, Anouk Slaghekke, Anneke Ellens, Kasper Janssen, Rob CI Wust

Objectives
Patients with Long COVID experience disabling fatigue, autonomic dysfunction, reduced exercise capacity, and post-exertional malaise (PEM). Heart rate variability (HRV) can evaluate autonomic function and monitor overexertion, potentially helping to mitigate PEM. This study aimed to use continuous multi-day HRV recordings to monitor overexertion and study autonomic function in Long COVID.

Method
Heart rate and HRV were continuously measured in 127 patients with long COVID (43+/-11 years, 32% male) and 21 healthy controls (42+/-13 years, 48% male), and daily life activities tracked in a logbook. Participants underwent a (sub)maximal cardiopulmonary exercise test to determine heart rate at the first ventilatory threshold (VT1) to study HRV responses to exercise at different intensities.

Results
HRV was lower in patients with long COVID compared to healthy controls during various daily activities and sleep (p<0.027). HRV remained lower for 24 hours after exercise below, at or above VT1 in patients, but not in healthy controls (p=0.010). Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p=0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.

Conclusion
Heart rate variability, assessed by wearables, confirms autonomic dysfunction in patients with long COVID. The delayed recovery of the sympathovagal balance after exercise close and above to VT1 suggests that VT1 can be practically interpreted as a PEM threshold. Application: These results confirm the applicability of wearables to assess autonomic function and manage overexertion in long COVID patients.

Link | PDF (Preprint: MedRxiv) [Open Access]
 
forestglip said:
HRV remained lower for 24 hours after exercise below, at or above VT1 in patients, but not in healthy controls (p=0.010). Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p=0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.
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I think the paper might be overstating some findings in general. But this is genuinely interesting. Would like to see it compared to other chronic illnesses instead of healthy controls.
 
EndME said:
That is really quite a large amount of people doing a CPET. I hope they managed to collect some other data as well.
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It looks like they might have only done a submaximal CPET:

Current optimal treatment to avoid PEM in patients with long COVID includes avoiding overexertion, and as such, long COVID participants were instructed to avoid exercise above the heart rate at the first ventilatory threshold. This was determined in a submaximal exercise test on a bike, three to six weeks prior to the HRV assessment.​

Adverse effects from the CPET
Three patients from this cohort experienced PEM for more than 5 days after the submaximal CPET. More than 5 days was considered an adverse event, because of the prolonged negative impact on daily life.​
 
Utsikt said:
It looks like they might have only done a submaximal CPET:

Current optimal treatment to avoid PEM in patients with long COVID includes avoiding overexertion, and as such, long COVID participants were instructed to avoid exercise above the heart rate at the first ventilatory threshold. This was determined in a submaximal exercise test on a bike, three to six weeks prior to the HRV assessment.​

Adverse effects from the CPET
Three patients from this cohort experienced PEM for more than 5 days after the submaximal CPET. More than 5 days was considered an adverse event, because of the prolonged negative impact on daily life.​
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Yes. But it's still quite a large setup, not sure if you'd do it if you're only interested in HRV data.

There's quite a lot of talk on PEM, but it seems PEM symptomology was not recorded as part of the study setup (in recuitment yes, but not as part of the study?). Hard to understand what this is supposed to tell us if patients are reporting PEM resulting from all sorts of activities not in anyway related to heart rate increases...
 
Mij said:
COVID patients had lower HRV during daily activities & sleep

HRV remained lower for 24 hours post-exercise, indicating delayed recovery

intense or prolonged exercise worsened subsequent nighttime HRV, a possible PEM-related symptom
https://twitter.com/user/status/1902620715360067701
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forestglip said:
Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p=0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.
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Purely mechanistically, would we expect something like nighttime clonidine to increase nighttime HRV and thus potentially aid recovery? Or would something like pyridostigmine mechanistically be of more help? I haven't been able to read the study and am wondering if they hypothesize whether its a SNS overactivation or a PNS underactivation they're seeing?
 
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To me this paper seems to really show something. Big sample, clear results. HRV is depressed for a long time after exercise in patients but not controls. And more strongly depressed in more severe patients.



Screenshot 2025-04-20 at 9.13.14 pm.png

Blue dots are the time when hrv shows a significant rise from baseline; it takes much longer in patients.

The reason the paper talks about 24h after is that's how long they measured for, but I suspect you could measure for a week and find out whether reduced HRV correlates with subjective PEM or with any other measures (cerebral bloodflow, Heart rate, immune markers, metabolic markers, etc).

If we had an objective measure of when PEM was finished that could be very helpful, stop some people getting into rolling PEM.
 
EndME said:
That is really quite a large amount of people doing a CPET. I hope they managed to collect some other data as well.
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I was excited there might be more papers forthcoming but it looks like this is a retrospective study of data collected at a clinic. Which is why there's so many patients (127) relative to controls (21).

Honestly I'm impressed by it.

incidentally this is the tool they used:

Bodyguard 3 device (Firstbeat, Finland). It costs Euro268, and the website makes it look quite well developed. When these guys figure out there's 10 people with chronic illness for every one professional athlete, they could pivot to being a health company primarily!

Screenshot 2025-04-22 at 10.20.14 am.png
 
Utsikt said:
I wonder how HRV would correlate with PEM if you never get close to your VT1, e.g. low intensity physical activities over a long period of time. Surely that could also trigger PEM?
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n=1 here of using HRV to guide pacing and avoid PEM. especially overnight HRV. Clear association with reduced HRV and need for better pacing and avoiding a crash. My Garmin has been keeping me well, without it I'd be PEMtastic. I also use the body battery function which incorporates HRV and HR. I also use it to check effects of supplements/meds. Eg naltrexone increased my overnight HRV.
I used to use it for multisport to run marathons and long distance biking, to avoid overtraining when I trained 2-3 times per day and guide when to have recovery training sessions. Now using it for the same thing just at obviously at much lower level of activity eg do I need to walk or crawl up the stairs when I was at my worst
 
Kiwipom said:
n=1 here of using HRV to guide pacing and avoid PEM. especially overnight HRV. Clear association with reduced HRV and need for better pacing and avoiding a crash. My Garmin has been keeping me well, without it I'd be PEMtastic. I also use the body battery function which incorporates HRV and HR. I also use it to check effects of supplements/meds. Eg naltrexone increased my overnight HRV.
I used to use it for multisport to run marathons and long distance biking, to avoid overtraining when I trained 2-3 times per day and guide when to have recovery training sessions. Now using it for the same thing just at obviously at much lower level of activity eg do I need to walk or crawl up the stairs when I was at my worst
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What kind of watch do you have?
 
AI said:
Heart rate variability (HRV) generally decreases during exercise and recovers faster in individuals with higher levels of fitness. This is because a more efficient cardiovascular system, characteristic of higher fitness, allows for quicker recovery of parasympathetic nervous system dominance after exercise.
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I haven't looked at the paper yet - it does look interesting. But, I wonder if what we are looking at is just the difference between fit people and people who are deconditioned? That AI result I posted above suggests that it could be.
 
I haven't read the full paper yet, but the abstract seems to be equating low HRV to PEM. I don't think that has been established in either direction. (I once played with HRV long time ago and I wasn't able to correlate HRV to my PEM). As for VT1 or VT2 as the PEM threshold, there has long been the claim of anaerobic threshold as PEM threshold. I don't think that has been proven either. Most severe/moderate patients won't be able to reach that level before triggering PEM.
 
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