Q&A Report: Autonomic Dysfunction in Long-COVID

Have you seen changes in profiles of post COVID patients who already had dysautonomia?

Interestingly many of the patients we see had features of orthostatic intolerance prior to Covid and this has been replicated in other case series (Blitshteyn and Whitelaw, 2021). However none of our POTS/VVS cohort have had persistent symptoms following Covid – it would be interesting to follow these individuals.

You can modify your breathing pattern and this will change your heart rate?

Thank you, and we agree. A predominant feature of many of the patients we have seen is a dysfunctional breathing pattern which may also be contributory. This also forms the basis of breathing exercises to optimise respiratory sinus arrhythmia and heart rate variability biofeedback to allow the user to maximise this.

During HUT her pulse pressure obtained with continuous BP decreases. This suggest decreased blood volume. Her orthostatic tachycardia could be a normal compensatory response to decreased blood volume.

Decreased blood volume is one of the predominant features of this condition, and is likely to contribute to her symptoms, which had been going on for some months. They were reproduced exactly when she was tilted. Thus hypovolaemia is highly likely to be contributory and underpins the conservative advice to ensure fluid and salt repletion, and the pharmacotherapy rationale of fluid expanders such as fludrocortisone.

Time duration post covid autonomic dysfunction - how long does patient normalise in your experience?

Anecdotally, we see a trend of improvement over 6-12 months, both with and without pharmacotherapy. We have seen some patients get a second Covid infection, which caused a further deterioration in symptoms but do seem to improve with conservative measures and occasionally pharmacotherapy.

What is the frequency of the blood pressure oscillations? Has this data been assessed by a fast fourier transform analysis?

The period is typically between 8 and 12 seconds for a complete cycle, (f ~0.1Hz) . We have not applied FFT to these data.

If you don't have a tilt table, can you capture data during the NASA Lean Test which can easily be done in the clinic setting?

Yes this is possible, but ideal to have non invasive Beat to beat BP and HR recordings, to track the fluctuations in BP and HR.

Since an increase in LF modulation of blood pressure is expected in healthy subjects after tilting, how much increase in the LF of blood pressure can be assigned to dysautonomia?

It is a good question and we have not analysed the data carefully. The observation though is that the amplitude of the LF oscillations are increased and my expectation is that the proportional area under the curve of the whole power spectrum density map would be enhanced in the LF frequency domain. This needs to be analysed. My expectation is that the patient would POTS would also demonstrate a similar physiology and proportional increase in the overall LF frequency.

Is the autonomic dysfunction independent of the severity of COVID infection?

So far, it seems that the two are independent, with many patients experiencing relatively mild initial infection (certainly not requiring hospital admission) but severe symptoms following infection. It may be that underlying predisposition to orthostatic intolerance may be a stronger risk factor (for example, joint hyper-mobility syndrome).

Do you measure cerebral blood flow autoregulation?

We don’t measure it in our group, and to our knowledge others haven’t studied it wither in Long COVID, but we agree this would be interesting.

Can the COVID vaccine initiate some of these responses and have you seen it ?

Overall the evidence points to a significant reduction in Long COVID in individuals who have had the vaccine. There may be a mild exacerbation immediately following vaccination if the individual has a fever, or dehydration. There is one case report to our knowledge of a patient developing POTS following the vaccine. However we advise our patients that the benefits far outweigh the risks, both in terms of avoiding fatal complications of acute infection, and also avoiding repeat COVID infection and its associated post-infectious sequelae.

So blood pressure lability in the transient phase is one of the features? Sustained lability?

I do not think this is blood pressure lability in the common sense of our usual understanding of both high and low blood pressures at various times of the day to define blood pressure lability. Rather this is an enhanced oscillatory pattern with a low frequency domain which occurs fairly reproducibly and regularly. The enhance oscillations, I would suggest our not necessarily to do with blood pressure lability.

Have any of these symptoms been found after vaccination without being infected with SARS-CoV-2?

We have seen some patients develop mildly worsened symptoms following the vaccine, probably from the associated fever and dehydration. There is one case report to our knowledge of a patient developing POTS following the vaccine. However we advise our patients that the benefits far outweigh the risks, both in terms of avoiding fatal complications of acute infection, and also avoiding repeat Covid infection and its associated post-infectious sequelae.

Anti-histamines is such a great repurposing example? Please can you explain the plausible mechanism?

Great question and I wish we knew the answer. My best speculative opinion is that stress (aka mediated by the activation of the adrenergic response from orthostatic intolerance, and possible vasodepression) and the consequent adrenaline release does appear to sensitize the mast cells and make them more susceptible to spontaneous degranulation with a lower threshold. This is commonly seen in dermatological conditions where stress is known aggravating factor in condition such as hives or spontaneous chronic urticaria. The mechanisms here with chronic orthostatic intolerance triggering the adrenergic surge and consequent release and adrenaline may well give a similar phenotype and this is why antihistamines may be useful. Anecdotally I found at one of the interesting things about antihistamines as that this improves sleep dramatically as well.

Would a rise in HR and a rise in BP not point towards anxiety rather than actual autonomic dysfunction?

This is the enduring question of many lifetimes: Does the chicken or egg come first?

Did these individuals have any chronic diseases known or not known until seen post-covid? Any relation to tobacco use? Any changes in profusion of major nerves post-COVID?

Most of the patients we described had no underlying chronic diseases, and were generally non-smokers with minimal alcohol use. We have not tested neural function but others (eg Hinduja et al 2021) have done.