Is orthostatic intolerance a normal (and underdiscussed) acute infection response?

[jnmaciuch]

Just an idle thought I had from thinking about CNS-mediated symptoms of infection. The symptoms that seem to get the most discussion are general malaise, fatigue, chills, fever, heart rate, and cognitive impairment. It made me wonder: do people normally also experience orthostatic intolerance during an infection and just not register it as a specific symptom?

Thinking back to the worst infections I’ve had, I do remember a preference for lying in my bed. Once I got to the point where I could migrate to the couch and watch some TV, that tended to be a sign I was on the way to recovery. I also distinctly remember feeling a cold coming on while I was stuck at school and needing to put my head on the desk or find a corner to lie down during break times. My sense is that if it was just fatigue, closing one’s eyes while being supported upright would have similar relief as lying down. And yet the thing that tended to define the worst phase of being sick was collapsing into a pile of misery.

I’ve done searches in the literature and it seems like no one is really discussing “orthostatic intolerance” as a specific feature of infection response. So the question I’m throwing out is whether this is because it’s an under-recognized feature, or if it’s just not a feature at all.

Folks who experience orthostatic intolerance: is there any similarity to how you might’ve felt during the worst flu of your life pre-ME/CFS? Do you notice that family members who come down sick start resembling your OI symptom patterns? For the medical professionals who have treated lots of infected patients: do you see patterns that might be reasonably described as OI?

I think this question is relevant because it could tell us whether this prevalent symptom of ME/CFS can already be explained by the pathways involved in infection response, or if any theory of ME/CFS has to reach beyond that to explain OI.

 

[InitialConditions]

I never experienced the main OI sensations I now get, prior to their onset in 2023. All I can say is it feels different to wanting to be supine and rest during pre-ME viral infections, etc, which is essentially just sickness behaviour.

My OI is very distinct, sometimes subtle, sometimes not, heaviness or fatigue centred in the chest / around the heart — like my heart is struggling a little. Along with other symptoms, such as blood pooling.

 

[hotblack]

What I began to experience with ME/CFS in terms of OI was unlike anything I’ve experienced before with any sort of illness or infection apart from perhaps myocarditis. I used feel tired and have a desire to lie down with illness/infections but not anything close to the level of discomfort and urgency or symptoms like chest pain, light headedness, circulatory problems etc.

The severity of OI was one of the most significant features for me from early on, I know not everyone has OI and what feels like cardiovascular issues quite like this, but I’ve certainly heard quite a few others describe similar.

To me it’s more like the difference between the fatigue we get and the ‘feeling tired’ people who are ill get. They could be said to be sort of the same in some ways, certainly from the outside observer, but also feel really quite different and incomparable with many saying it’s a fatigue unlike anything they’d previously experienced.

I don’t know definitively if they’re the same or different, if they are all on a range of severity or some other factors combine to make them feel different. But all I can say is they feel different.

 

[Kitty]

Folks who experience orthostatic intolerance: is there any similarity to how you might’ve felt during the worst flu of your life pre-ME/CFS?

I don't think so.

OI can be one of the symptoms of a viral infection, but there isn't the dire urgency you get in ME/CFS. The need to sit or lie down is like having something in your eye—you can't pay attention to anything else until you've sorted it.

 

[Mij]

My OI is very distinct, sometimes subtle, heavinness or fatigue centred in the chest / around the heart — like my heart is struggling a little.

My experience from being upright for too long is chest and forehead pressure. It's very uncomfortable I feel the need to down immediately, but that's not always possible depending on where I am. I recover and feel ok after lying down for under an hour.

I contracted Covid, reactivation of EBA and HHV6, but never felt orthostatic intolerance and the immediate need to lie down with any infection.

 

[Jonathan Edwards]

It made me wonder: do people normally also experience orthostatic intolerance during an infection and just not register it as a specific symptom?

I think that orthostatic intolerance, as widely construed, is so pervasive a feature of poor health that it probably does not get put in the infection list (a) because it is non-specific and (b) because it isn't so much a symptom per se as a need to respond to a symptom. That symptom might be nausea, faintness, weakness, vertigo, headache, kidney stone pain or whatever.

Most of the seriously ill people I have managed in hospital cannot tolerate being upright.

What may be true of ME/CFS OI is that, as @InitialConditions suggests, it is out of proportion or a bit different. But that is hard to pin down.

 

[Jonathan Edwards]

OI can be one of the symptoms of a viral infection, but there isn't the dire urgency you get in ME/CFS.

I think there often is, for really ill people. People with meningitis or septicaemia or just a nasty virus. In the days when I had typhoid vaccine I was forced to lie down very suddenly about an hour after the injection. That is the paradigm of "sickness response".

 

[SugarSquared]

I never experienced OI in the way that I do now before getting ME/CFS. Sometimes I would get lightheaded and need to lay down, but it’s the kind of lightheaded you get before fainting which I did as a child. This OI is a mix of nauseous and lightheaded, but that’s just the closest approximation that I can get. It really feels like its own thing where I feel physically ill when sitting upright or standing.

 

[hotblack]

The infection that triggered everything for me was kidney stones, a kidney infection that wasn’t handled well by people and got out of hand and sepsis that was thankfully handled well. And I was so out of it in that that I couldn’t stand and was being wheeled around. And while recovering wanted to lie down. Now, it’s difficult to remember clearly to be fair, things were pretty messy. But I still feel what came after, what developed in the following months as I recovered from that but then went downhill with ME/CFS and what I now describe as OI, was, or at least felt and was experienced by me, as different.

 

[Mij]

I forgot to mention that I also feel chilled/cold/shivery when being upright/OI for too long.

 

[jnmaciuch]

Thanks for the responses so far @hotblack @InitialConditions @Kitty @Mij @SugarSquared.

Helpful to know it’s definitely much more intense than a common flu. I guess the crux of my question comes down to this:

What may be true of ME/CFS OI is that, as @InitialConditions suggests, it is out of proportion or a bit different. But that is hard to pin down.

is it out of proportion (and ME/CFS level OI is only matched by the sickest of the sick), or does it actually have different features that don’t tend to occur with any infection? I’m not sure if there’s a good way to answer that if someone hasn’t experienced both

 

[Felis Catus]

I experienced something similar during mononucleosis but I wouldn't say it was the same as what I've experienced with ME/CFS.

Back then I was horizontal for a month except for going to the bathroom and hospital for the blood tests. I was fed in the bed, head just slightly inclined on the pillow. I had to be carried to the bathroom and held on the toilet. Similar with the hospital trips.

The main differences:
- It felt different. It felt like my body was too weak to hold itself upright. I wasn't getting any sensations in my back or head when other people kept me in a seated position. I don't remember my breathing changing or anyone commenting on it. No feeling of pushing through.
- Trips to the hospital made me worse on the day but I don't remember feeling worse on the following days. Sitting in the bed for a few minutes with severe ME/CFS has been triggering an immediate response as well as PEM.

I spent the second month of recovery from mono largely sitting in the bed. I'd say it was fatigue and the feeling of weakness that kept me in the bed. I don't remember having any other symptoms apart from cognitive difficulties which I didn't ascribe to the body position because I also had them during the first month when I was horizontal.

When I started going out, I didn't feel dizzy and nauseous, didn't experience vertigo - all of which I experienced in the early months of ME/CFS.

I fully recovered.

TL;DR It felt different back then, primarily as a weakness. I could sit up when necessary if someone held me. Now someone holding me wouldn't help.

 

[jnmaciuch]

The infection that triggered everything for me was kidney stones, a kidney infection that wasn’t handled well by people and got out of hand and sepsis that was thankfully handled well. And I was so out of it in that that I couldn’t stand and was being wheeled around. And while recovering wanted to lie down. Now, it’s difficult to remember clearly to be fair, things were pretty messy. But I still feel what came after, what developed in the following months as I recovered from that but then went downhill with ME/CFS and what I now describe as OI, was, or at least felt and was experienced by me, as different.

Thanks, these are useful details. Do you mind clarifying what exactly was new compared to your sepsis episode

 

[hotblack]

Thanks, these are useful details. Do you mind clarifying what exactly was new compared to your sepsis episode

@Felis Catus describes something similar I think. I’ll try and write something more over the next few days and send it to you.

 

[jnmaciuch]

@Jonathan Edwards is tachycardia a normal feature of infections? I know it can definitely occur along with other symptoms, but as far as I know it’s not universal (and I'm vaguely remembering something about about bradycardia being a specific feature of some sepsis cases). I ask because I'm wondering about the possibility of ME/CFS involving an imbalance of infection response signals rather than something additional to explain OI, just like how those signals might cumulatively affect other aspects of the autonomic system during infection. So ME/CFS OI might be severe infection OI minus one or two of the normal "brakes" that come from other parts of the infection response.

 

[neophyte32]

Before the prodromal phase of my ME/CFS, or before the mild phase, I had never, ever experienced orthostatic intolerance. In fact, I very rarely got sick.
When I had my first COVID infection in 2020, I only spent one day in bed. That said, I do remember that the few bouts of gastroenteritis I had before the onset of my ME/CFS made me want to lie down and stay in bed. I am saying this from memory, of course. But isn’t that simply a normal reaction when you have gastroenteritis ?

My ME/CFS was probably caused by a combination of different factors : too many medications, tramadol, perhaps a bit too much alcohol, a COVID infection... In truth, I do not know, and I suspect I never will, especially because my ME/CFS began about seven months after my last COVID infection.

What really made me realize that I was not simply experiencing burnout, but that something physical was clearly wrong, was the onset of orthostatic intolerance. This appeared a little over a year after the beginning of my ME/CFS, when I was still only mildly affected.
Several things happened around that time : one evening when I drank too much alcohol, exercising three days later, a panic attack, as happened almost every time I tried to exercise after the onset of ME/CFS, and then taking antidepressants.
I stopped the antidepressants only ten days after starting them, and immediately afterwards I developed what clearly felt like POTS.

What do I feel when I am standing ? It is quite difficult to describe. I get a strange empty-headed sensation, together with pressure in my chest. And of course, I also have postural tachycardia, often with my heart rate above 100 bpm. Typically, it goes from around 60 bpm lying down to somewhere between 70 and 110 bpm when upright. Strangely, I do not really have hypotension.

Everything used to become much worse when I tried to exercise upright, which ultimately worsened my ME/CFS : a feeling as if I were going to die, burning in my chest, an empty-headed sensation, and a very high heart rate, around 160 bpm even while jogging slowly.

Now that I am very severely affected and bedridden about 23.5 hours a day, my heart rate rises to around 95–100 bpm when standing, compared with about 58–65 bpm lying down, despite taking a low dose of nebivolol. My tinnitus becomes roughly twice as loud, I develop the same empty-headed feeling, frontal pressure, and pressure in my chest.

I cannot remain standing for more than about two minutes.
I also cannot sit upright for more than around five minutes, because I develop the same symptoms, although somewhat less intensely.

 

[Jonathan Edwards]

I ask because I'm wondering about the possibility of ME/CFS involving an imbalance of infection response signals rather than something additional to explain OI, just like how those signals might cumulatively affect other aspects of the autonomic system during infection. So ME/CFS OI might be severe infection OI minus one or two of the normal "brakes" that come from other parts of the infection response.

This is how I am reading it too.
The teaching was that sepsis from bacteria causes tachycardia. Viral infection is more likely to show bradycardia, or perhaps just normal rate. POT is obviously a bit different from typical sickness behaviour but then a lot of ME/CFS OI is said not to be POT and your pick 'n' mix model might cover it anyway.

 

[hotblack]

Do people think it could feel or be experienced very differently although be a similar underlying mechanism then? Or that combination of factors I mentioned before to? What some of us seem to be describing is an outsized bodily response to what some may characterise as a normal infection response, but happening abnormally (without the presence of an infection). If that makes sense…

To me it’s not just say an elevated heart-rate but more it’s that my body responds really really badly to an elevated heart-rate now compared to how it did before ME/CFS.

 

[jnmaciuch]

This is how I am reading it too.
The teaching was that sepsis from bacteria causes tachycardia. Viral infection is more likely to show bradycardia, or perhaps just normal rate. POT is obviously a bit different from typical sickness behaviour but then a lot of ME/CFS OI is said not to be POT and your pick 'n' mix model might cover it anyway.

I wonder if drug companies might already have the combinatorial-symptom-profile information. Interferon certainly isnt the only recombinant cytokine that was trialed for chronic infections, cancer, etc. I’m guessing the vast majority of them just went the way of most drugs, either didn’t work very well or had too much of a risk profile. But combination therapies were all the rage, so it’s possible some companies may have already tested IFN-B + IL-6 + TGF-B or what have you.

A look through the archival documents from phase 1s might show a list of descriptors pretty similar to how folks here are describing their OI. We might even get lucky and find the combination that checks off all the symptom boxes. Though I think companies tend to be pretty protective of their historical records so this might not get very far

 

[StellariaGraminea]

Just an idle thought I had from thinking about CNS-mediated symptoms of infection. The symptoms that seem to get the most discussion are general malaise, fatigue, chills, fever, heart rate, and cognitive impairment. It made me wonder: do people normally also experience orthostatic intolerance during an infection and just not register it as a specific symptom?

I rarely got sick previously, but I can remember feeling weak and "faint" in the recovery phase after previous infections, and having to sit down, maybe even lie down. But following Covid it was in a totally different league. I can't say if it was just more extreme on a continuum of OI or another thing altogether. However it was v distinctive to me, particularly the overpowering urge to "get flat", the sense I was literally going to die if I stood up too long. Not in a morbid or fearful sense but more from feeling so deathly ill being upright.

After ? 5years it improved so I don't often have that urge and what I have now feels more akin to the recovery phase after previous infection... except that it never improves beyond that, and also goes through random phases of worsening.