Signs, Symptoms, Complaints & Claimants: A Medical History view of "Long Covid"

From Neurosyphilis, to Schizophrenia, to Chronic Fatigue and to "Long COVID"

Rudolf Virchow, 1821-1902. Widely considered the “father of modern pathology.”

This guy right here.

Rudolf Virchow was an interesting character. A German physician, but also a bit of a jack of all trades, he dabbled as well in anthropology, history, and even politics and social reform.

One of the things his corpus of work was known for was reorienting the modern medical field away from the old-school “humoral theory” of illness (e.g., that illness was caused by imbalances of the four humors: black bile, phlegm, yellow bile, and blood) and towards the modern, histopathologically-driven notion of medical disease.

Virchow’s achievements were nothing short of monumental - he was famous for obsessively introducing the use of microscopy into the training and practice of medical students, encouraging them to “think microscopically.” He was a prolific publisher and was well-known to have started numerous professional societies.

He also stood (sadly, futilely) against some fairly virulent ideological strains of thinking that were beginning to take root in German society, such as that of eugenics and “Aryan superiority,” and interestingly, was a fierce critic of Darwin’s Theory of Evolution.

The Virchowian Clinical Logic

One of the true advances in Virchow’s thinking is that to identify a disease entity we need to have a pretty clear sense that we are identifying an underlying pathophysiological abnormality that is driving the complaints or symptoms one sees as a clinician.

Think of this like “levels of evidence,” with physicians and diagnosticians working as detectives. The detective is trying to suss out the criminal, the pathophysiological abnormality. This is the lesioned tissue, or abnormal clump of cells caused by an injury, or malignancy, like cancer. Whatever it is - there’s something physically wrong underneath - and they lead to all the things below

1. There’s clinical signs - for example, the tell-tale blistering and spotting seen in chicken pox, or an elevated temperature. While the meaning of the signs may be up to some interpretation, their existence is observable and objective. Clinical signs cannot be faked, they are simply just there.

2. Somewhat related to the above are laboratory tests, such as a positive tuberculosis screen, or a suspicious pap smear. Again, interpretation of data (as well as calibration, reliability, and validity) are all key - but again, these lab tests are objective indicators.

3. Then there’s clinical symptoms. This is where things get a bit dicey. Things like a limp, rapid blinking of the eyes, or limb weakness. While these things are on one level observable - and to a certain degree, objective - they also are subject to voluntary control and therefore aren’t as useful as a clinical sign or a laboratory test.

4. Finally, there are clinical complaints. This is the most subjective of all. Things like complaints of chest pain, or sad mood, or anxiety. While these are valuable, these clinical complaints are some of the weakest forms of evidence that the “medical detective” has in finding the pathophysiological culprit - simply because they, to put it bluntly - so easy to manufacture.

Neurosyphilis - a Major Triumph of Modern Pathophysiological Clinical Science

Getting back to medical history - one of the most public tests of Rudolf Virchow’s approach to disease identification can be found in the case of neurosyphilis (yes, the venereal disease). This is considered one of the triumph’s of modern-day clinical science - particularly due to the fact it was so difficult to figure out early on in the 1800s & earlier, and was often misidentified as simply “insanity” - the stuff dealt with by psychiatrists (called “alienists” at the time, interestingly), and often written off as the consequence of “weak character” “moral turpitude” in the sufferer.

Yet it was in 1913 that a Japanese bateriologist Hideyo Noguchi, working at Rockefeller University in New York - actually discovered via the rudimentary lab testing approaches available at the time that so-called “general paresis” - what we now know of as neurosyphilis, was caused by the introduction of syphilitic spirochetes into the bloodstream, AKA Treponema pallidum. This pesky little pathogen (picture below) is what caused the various primary, secondary, latent, and tertiary stages of syphilis.

Treponema pallidum - there’s the culprit.

The Triumph of Syphilis Changed Psychiatry

One of Rudolf Virchow’s most famous quotes: “Medicine is a social science, and politics is nothing else but medicine on a large scale.”

To that end - the triumph of Virchowian pathophysiologically-based medical science was clear - all things that are the purview of medicine are, ultimately, the objectively-identifiable dysfunctioning of material, physical things.

In a weird way - the “triumph of syphilis” gave birth to the modern ideas of biological psychiatry - that is to say, “all mental illnesses are brain diseases” (a quote attributed famously to Nobel laureate Eric Kandel.¹

It’s a strange twist of logic. Because medicine so clearly hit a home run by eventually identifying that so-called general paresis was not, in fact, caused by “poor moral character” but instead was caused by syphilitic spirochetes invading the blood - the idea now is that anything that medicine declares a disease, as long as it’s done authoritatively, should eventually yield a reliable and valid set of pathophysiological markers in the same way.

Obviously - medicine didn’t “declare” neurosyphilis (known alternatively as tabes dorsalis) to be a disease - the clinical scientists at the time had to actually go through the work of delineating the characteristic symptoms and then finding out the proximate cause. They did the work.

But remember - medicine is a political discipline as much as it is a discipline of clinical science. Virchow knew this. And with the triumph of syphilis - institutional medicine received a huge political shot in the arm.

They, by virtue of the authority vested in them - were the arbiters of what was disease, and what was not.

Schizophrenia - The Ultimate Biological Psychiatric Illness with no known Cause

Schizophrenia, despite not ever having a clinical "gold standard" diagnostic sign (e.g., like a blood test or a definitive structural abormality identifiable on an MRI or CT scan) has been promulgated as a standalone, distinct bona-fide disease entity based almost entirely on the "syphilis metaphor" - that is to say, much like general paresis eventually become known as neurosyphilis due to the pioneering work of neuropathologists, schizophrenia will eventually be similarly validated, once enough research has been done.²

Obviously - for any number of people suffering from so-called schizophrenia, if you have worked with them (and I have, for a number of years in my clinical practice) - you do get a sense that at least for some of them, there is something wrong, and in fact it may be biologically based. It's even possible that someday, with all the untold billions (trillions, likely, in inflation-adjusted dollars) that has been spent on basic research, something akin to Treponema pallidum may be found to underly what causes these strange behaviors and issues with people identified as schizophrenic.

But - even after all these years - we aren’t there yet, and that’s telling.

Either there’s something wrong with the Virchowian model of disease - or there’s something wrong with the modern-day idea of putting the proverbial cart of disease identification before the pathophysiological clinical science horse.

Psychiatry may be a special case - at least for the sake of argument. So let’s leave this issue aside because this could take us down a pretty significant rabbit hole.³

Chronic Fatigue Syndrome (CFS) - The Poster Child of Medical Syndromes

This is not an area of expertise of mine, so you’ll have to bear with me.

CFS, also known as “encephalitic myalgia” was something that was described formally as early as apparently 1988 (a good brief history is here) but apparently various outbreaks of CFS-like illness have been documented since the 1950s.

In CFS, people complain of severe fatigue, to the point of not being able to get out of bed. Body aches, headaches, “post exertional malaise” are common, along with a number of other vague but troubling complaints and symptoms.

Apparently was called “Epstein Barr like” illness (because it mimicked the symptoms of the same infection) - although in this case, there is, as you might expect - no actual underlying virus or infectious agent that’s identifiable.

There’s controversy about CFS, of course. Early on, physicians tried to label & dismiss sufferers of CFS as having “myalgia nervosa” and later, & more derisively, “yuppie flu” (because the sufferers seemed often to be disproportionately drawn from the ranks of young, urban professionals in metropolitan areas).

However, instead of being dismissed - CFS eventually became what turned out to be a powerful contemporary example of successful patient activism. Over time, CFS claimants banded together, and convinced the CDC and other government funding agencies that despite the doubts of the medical establishment & the lack of success of earlier research efforts to find an actual cause for these “complex” and vague (but at times, apparently quite severe) complaints & symptoms suffered, that CFS was to be regarded a bona-fide clinical entity that was to be regarded as no less legitimate than any other chronic ailment - despite (even today) there being no known actual underlying pathophysiologic abnormality that reliably explains the various complaints and symptoms that make up the syndrome of CFS.

Long Covid - the CFS of our Time?

Enter “Long COVID” (LC).

The first mentions of LC can be traced back to, of all places, a blog that first appeared on the scene in 2018, called the “Body Politic Wellness Collective,” what was originally billed as a “queer feminist wellness collective merging the personal and the political,” and could fairly be described as a psychic crystal healing blog, where people got together to trade alternative theories and treatments about whatever they thought ailed them.

In 2020, the blog added on a “Body Politic Covid-19 Support Group” function to their website, and began “cultivating patient led research” which culminated in what seems most politely described as hopelessly confounded survey research (for one thing, the survey included LC symptom reporting data from significant numbers of people who reported zero previous COVID infection) which ended up predictably identifying a significant number of lingering, persistent problems they described as “long COVID” related.

Despite the at best shoddy quality of the research (and the questionable source) this didn’t stop previous NIH Director Frances Collins from taking great interest in the blog and later helping to push through over a billion dollars (and counting) in LC research.

The gift that keeps on giving. Photo by Volodymyr Hryshchenko on Unsplash

What is “Long COVID”?

According to the CDC, “long COVID” (or LC for short) can last for weeks or months “or longer.” It can result from a severe, mild, or even asymptomatic COVID infection (in other words, you don’t need to even have been sick with COVID to have it).

Symptoms include:

• Tiredness or fatigue

• Symptoms that get worse after physical or mental effort (also known as “post-exertional malaise”)

• Fever

• Difficulty breathing or shortness of breath, or cough

• Chest pain

• Rapid heartrate

• Complaints of “brain fog” or poor concentration

• Headache

• Sleep problems

• Dizziness when you stand up (lightheadedness)

• Pins-and-needles feelings

• Change in smell or taste

• Depression or anxiety

• Diarrhea

• Stomach pain

• Joint or muscle pain

• Rash

• Changes in menstrual cycles

And this isn’t even an exhaustive list.

BTW - what you’re looking at a list of essentially mostly clinical complaints, a few nonspecific clinical signs (e.g., rash, diarrhea), and otherwise, what you’re looking at is not really dissimilar from something that’s been around quite a bit longer (and may be more familiar to many of my USA audience): chronic fatigue syndrome (or CFS).

The big difference between CFS and LC, of course, is that LC is a set of persisting symptoms that are observed 12+ weeks post-acute COVID-19 infection, while the putative cause of CFS is still, as of yet, unknown (more on that later).

Long Covid as a “Mass Disabling Event”

Awash in anxiety

There’s been a lot of news about LC lately - and the argument that’s been heard increasingly is, particularly as mask mandates and those awful show-your-papers-please “vaccine passport” laws are starting to wane, we need to keep measures like this (particularly masks) because of the unique threat posed by the “mass disabling event” that is LC.

On the other hand, long before COVID was invented and released into the wild, chronic or persisting “post-viral illness” has been a thing, and can be caused by any number of respiratory or other viral illnesses like the flu, Epstein-Barr virus, pneumonia, etc.

Long Flu

Just as a random crawl through the literature, I stumbled across this gem, from The Lancet in 1994, which looked at the presentation of 618 subjects presenting to their GPs at clinics in London and other parts of England, after recovering from a bout of viral influenza (from the abstract):

GPs recorded fatigue in 62·6% of subjects, usually since the onset of symptoms. 502 (81·2%) subjects completed the 6-month questionnaire, of whom 88 (17·5%) met criteria for chronic fatigue and 65 (12·9%) had no reported fatigue before the viral illness. Compared with a similar group of non-postviral GP attenders, the risk ratio for chronic fatigue in the present cohort was 1·45 (95% Cl 1·14-2·04). Infective symptoms did not predict fatigue 6 months later. Psychiatric morbidity, belief in vulnerability to viruses, and attributional style at initial presentation were all associated with self-designated postviral fatigue. Logistic regression showed that somatic attributional style, less definite diagnosis by the GP, and sick certification were the only significant predictors of chronic fatigue after viral infection when other factors were controlled for.

Chronic severe fatigue 6 months after GP-diagnosed viral illness is related to symptom-attributional style and doctor behaviour, rather than to features of the viral illness. Some subjects with apparent postviral fatigue had complained of tiredness before their presentation with a viral illness.

It’s tricky - because on the one hand, there’s definitely something there. Like flu, or other viral illnesses - persisting chronic symptoms sometimes do occur.

But it’s clear there’s other things going on.

For example, apparently self-reported anxiety, depression, worry about COVID-19, and generally poor coping skills are actually a positive predictor of “having” long COVID symptoms.

Photo by Sherise Van Dyk on Unsplash

This isn’t something you’d expect to see in a bona-fide, real medical illness, is it?

Just sayin’…..

1. As an side - while the above on a certain level sounds very logically plausible, on the other hand calls into question why the field of psychiatry exists in the first place… why don’t we just have neurologists do everything psychiatry does….?

2. Note the 2022 budget of the National Institutes on Mental Health is currently around 2 billion dollars, with approximately 40% of that going to "basic research," if I have my numbers right.

3. If you want to travel down said rabbit hole - I highly recommend you try and get through a couple of books by Thomas Szasz, MD - the late great emeritus psychiatrist from Syracuse University. I write a bit about him here.