I wrote here about a recent effort to profile “long Covid” patients to look for differences in blood chemistry, immune function, and many more biomarkers. That study came up notably blank: the authors could find no difference between people reporting such symptoms and those who didn’t. And while that’s of great interest, it’s not going to settle the questions around post-Covid symptoms, either, far from it. Here, for example, is a new paper in Nature Medicine that analyzes data from the VA on vaccinated patients who went on to have coronavirus infections. Looking at them six months after the first 30 days post-infection, they find that these patients showed a lower risk for death and for various complications (cardiovascular, hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurological) than a matched group of never-vaccinated people who came down with the infection. That’s good to hear, but at the same time, their risk of all these complications (including death) were higher than a matched group of never-infected people. These are the sorts of numbers that keep the concept of “long Covid” going, and no wonder.

We’re surely going to end up classifying this with a whole list of other post-infection syndromes, the most well-known of which are Lyme and Epstein-Barr. Here’s a review of that area, and medically, it has always appeared to me to be a trackless swamp. The arguing about these has been literally going on for decades, and writers like Edward Shorter would say that it’s been going on for a lot longer than that. A recent memoir, Russ Douthat’s The Deep Places, is a vivid account both of what it feels like to have these symptoms (in his case, Lyme) and what it feels like to go around for years without people believing that there’s anything actually wrong with you. An excellent (sympathetic but skeptical) review of that book is here, from Freddie de Boer. Full disclosure: de Boer considers things like long-term Lyme disease to be a “boutique diagnosis”, driven by what he sees as a market for new disabilities, but it should also be noted that de Boer himself knows something about disability, having had his career nearly blown up at one point through poorly treated manic episodes. Overall, he ended up saying that Douthat’s book was excellent and affecting, but in the end “the most compelling and moving version of a bad argument”.

I have gone back and forth on these issues myself, and I know I’m not alone in that. That Nature Medicine review linked to in the last paragraph notes, as have many other observers, that the general symptoms of post-infection syndromes tend to be similar, and similar to others that have been grouped under the headings of chronic fatigue syndrome, fibromyalgia, and others. These are reported not only after Lyme disease, but after dengue, West Nile, Ebola, giardia, and more, and the common symptoms include fatigue (and difficulty with exertion), unrestorative sleep, difficulty concentrating, musculoskeletal pain, and general flu-like symptoms that come and go in severity. This commonality leads to two broad schools of thought: “this is a disease with a similar etiology brought on by immune response”, and “this is not a disease”. If you look at the side effects most commonly reported in clinical trials – and particularly the side effects reported in the placebo groups – you can come across fairly similar lists. It is very, very hard to pin this stuff down.

But to be fair, just because we have trouble grasping something or classifying it doesn’t mean it isn’t real. You can imagine that the immune system could indeed be altered post-infection, in some broad and general ways, leading perhaps to a low-level autoimmune syndrome. But the problem with that approach is that (as the long Covid study linked to in the top of this post showed) it has so far proven more or less impossible to find such autoimmune markers, at least not consistently. You end up saying “Well, there’s something off with the cytokines, although they all look within normal ranges, or there’s something wrong with the T-cell response, although we can’t find anything, or there’s. . . ” And that’s no good, either. You can see how these things remain unresolved!

So all I can try to do is to keep an open mind. I am willing to write some of the more relentless sufferers off as having mental problems, but certainly not everyone. And I will likewise classify some of the more relentlessly skeptical observers as being dogmatic for the sake of being dogmatic – but certainly not all of them. As a medicinal chemist, someone who’s spent his scientific career looking at specific causes of disease and trying to attack them, I very much hope that such causes can be tracked down for these post-infection syndromes. After all, there’s an awful lot that we don’t know about immunology, and while that’s often a cause for irritation or despair, it can in a case like this be perversely hopeful. Something may well turn up that lets us start to make sense out of all this. But you’d want to have more than that to offer, wouldn’t you?