Treating PIS and long Covid ∞

I write about Covid because Covid hurts.

There’s plenty of overlap between chronic pain and long Covid, which is just the most famous example of chronic health problems after an infection. Many cases of ME/CFS and fibromyalgia (chronic widespread pain) probably started with some kind of infection, and we know specifically that people are at considerable risk of developing chronic pain after Covid (along with much else), punctuating a major theme in the science of pain: pain is mainly a function of physiological problems.

Today I’d like to pass on some science-based tips for long Covid and other other post-infection sequelae — the PIS in the title — cribbed from a particularly trusted source, with many clarifying details, links, and an emphasis on the practical.

The NASA lean test and probiotics stand out as especially useful things to know about, and not just for people with long Covid.

Introducing my trusted source

That would be Dr. Daniel Griffin, who has been doing his weekly “Clinical Update” on the This Week In Virology podcast since early in the pandemic.

The TWIV podcast, and the affiliated Virology Blog, have been excellent resources on this topic; they were championing the interests of patients with ME/CFS long before the pandemic, most notably hosting David Tuller and his tireless work pointing out bad science, like the canonical example of the horrible PACE trial.

In episode 1088, Dr. Griffin did a little mini seminar on managing long Covid, and his approach to this topic is notably compassionate and rational. This is a doctor who is well aware that medicine can do harm even with reasonable ideas, if they are half-baked and not fully tested… never mind the ones that turn out to be overt nonsense.

Long Covid diagnosis (and the PIS thing)

• Long Covid is made of “PIS”: post-infection sequelae. Dr. Griffin uses this generic term to describe the long-term consequences of any infection, not just Covid. “It’s not a good acronym, though.” I beg to differ! Laughter is good medicine, so I will refer to “PIS patients” for the rest of this post (and then never again).
  • There is a very similar term, “post-acute infection syndrome,” with the less silly acronym PAIS. Maybe they decided it was a good idea to have an A in there.
• Dr. Griffin mentioned three conditions that can imitate long Covid: lyme disease (and post-lyme syndrome, another member of the PIS family), adrenal or thyroid dysfunctions, and pituitary cancer. Just some examples off the top of his head, just to make the point that not everything that smells like PIS is actually PIS.
• We now have an official Long Covid scoring system, but Dr. Griffin prefers to just form of an impression of whether a patient fits the WHO definition: “the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation.” Which is in turn really just the formal version of “feeling crappy for way too long.” Yeah, it’s not an exact science.
• There are two clinical tests that are useful and quite accessible:
  1. Blood oxygen saturation at rest versus activity. That is, your oxygen shouldn’t drop sharply with activity! Oxygen saturation monitors are widely available, so this is pretty easy to check for yourself.
  2. The NASA “lean test” to check for signs of postural orthostatic tachycardia syndrome (POTS), which is one of the more common PIS-sy glitches that probably drives many symptoms. And what is the NASA lean test? It’s a simple test that replaces the much more medical (and inaccessible) “tilt table” test for orthostatic intolerance: lie down for 10 minutes, then stand up and lean against a wall, mostly erect, but heels 6-8 inches from the wall and shoulder blades touching it: and stay there for ten minutes, or until orthostatic intolerance is clear (weak, lightheaded, etc). This does in fact show OI in long Covid patients (Isaac et al). (And why NASA?! They can certainly afford tilt tables! But low and zero gravity involves many weird effects on autonomic regulation of blood pressure, so they developed the most efficient POTS test they could.)

Treatments for long Covid that are kinda, sorta evidence-based

The diagnostic situation is tough, but treatment “gets even tougher.” There are still no examples of truly evidence-based treatment recommendations for Long Covid, but these are all at least better than speculation, at least a notch more than “promising” …

• We may not be able to “treat long Covid” per se, but there are some evidence-based treatments for some specific parts of long Covid, for some of the specific issues that arise in many cases: POTS, dysautonomia, cardiac arrythmia, and sleep apnea are all often manageable to some degree, and much better than treating nothing at all.
• We do at least have strong evidence of one important thing not to do, a common source of harm that can be avoided: we can identify and prevent the triggering of post-exertional malaise! People with PEM do not just feel “tired” after exercise, but ill, and pushing it can make them quite a bit worse. The evidence-based recommendation is: if there is PEM, then no exercise therapy! But if there is no PEM … then, yes to exercise therapy!
  • What about that new study? The one that said “cautious exercise rehabilitation should be recommended to prevent further deconditioning”? It’s getting cited to justify pushing long Covid patients to exercise — trying to sustain the legacy of the bullshit PACE trial. But the word “cautious” is critical here: this is a recommendation to preserve what fitness can be preserved without overdoing it. (Dr. Griffin discussed this paper in episode 1104.)
• Re-vaccination seems to be helpful in some patients, neutral in many, and (awkwardly) actually harmful in a few. That’s Dr. Griffin’s clinical impression, backed up by a new study (preprint). This peer-reviewed one from mid-2023 is similar, and generally confirms that vaccination has varied and unclear effects on pre-existing long Covid, but with enough positive signs that, at the very least, long Covid patients shouldn’t avoid vaccination.
• Probiotics! Maybe someday we’re all going to regret our enthusiasm for probiotics, but damned if it doesn’t actually seem promising. Dr. Griffin thinks this might be getting close to evidence-based (and likely other kinds of PIS patients). For instance, specifically, a cocktail of pre* and probiotics called “SIM01” has some fairly good preliminary support from a new trial: “Treatment with SIM01 alleviates multiple symptoms.”
  • But how do you get that? The tested cocktail is not something you can easily buy, if at all — Dr. Griffin mentioned a patient who had found a way to gt some from China, where the study was done. However, you probably can imitate it well enough. It contains three species of Bifidobacterium (bifidu, adolescentis, and longum), and the Bifidos are a bog standard genus of gut fauna, with many species featured in common probiotic products. The formula was based on the relative abundance of those species in healthy Chinese adults. The cocktail also contains some prebiotic compounds and dextrin (food for the bacteria to encourage them). So basically it’s just some common gut bacteria with some snacks they like. Dosage? The trial did 10 billion “units” twice daily for six months (but maybe start slow).
• Melatonin supplementation, finally, might be helpful — not as a sleep aid (it’s main reputation), but via various anti-inflammatory properties. And melatonin is pretty innocuous. Here’s a recent review, which characterises it as promising but “underexplored.”

More speculative treatment options for long Covid

Dr. Griffin then moved on to treatments “extrapolated from evidence, but still not evidence-based medicine,” and he wisely noted that “90% of our great ideas are ultimately not great ideas.” He didn’t go into much detail about these, and a couple were too speculative for my tastes.

Nattokinase, for instance, is a supplement from the slime of fermented soybeans. It is touted by some quacks to “detox spike protein” from vaccines. 🙄 There’s a more rational case for the stuff, but it’s weak sauce and probably won’t amount to anything.

And so on. From the long list of un-tested and barely-tested possibilities, something might pan out someday… but probably only a fraction of them.