When I sat down to discuss Joachim Gerlach’s paper on what he calls a spike-mediated compound immunodeficiency cascade, I knew the conversation would provoke strong reactions. The title alone does that. But for me, the most important part of the discussion was not the headline claim. It was the tension underneath it.
What I keep seeing — clinically and in population-level patterns — is that the picture does not fit neatly into simple immune deficiency. Something has changed. The characteristics of illness have changed. The way patients present has changed. Cancer presentation appears to have changed. Infection patterns look unusual. But the deeper question is whether we are looking at a weakened immune system in the classical sense, or one that is chronically activated, poorly directed, and increasingly unable to respond appropriately when it matters most.
That distinction is not branding. It is biology.
Why This Matters More Than Most People Realise
One of the first points that came up was the idea that all of this is behind us. I do not think that is true. I think it is one of the most dangerous assumptions in medicine right now. We have collectively behaved as if the acute pandemic phase ended, and therefore the biological consequences must have ended too. Those are not the same thing.
Joachim’s position was that SARS-CoV-2 is still circulating widely, that repeated exposure remains common, and that his group is seeing surprisingly high rates of spike positivity in blood samples — including in people without obvious symptoms. He described a survey using a finger-prick spike test in which asymptomatic individuals were frequently positive, with even higher positivity in symptomatic groups and in patients presenting with long COVID. His point was that persistent spike should not be dismissed as trivial background noise if it is continuously being detected.
I take this information seriously enough to interrogate that it fits a broader observation I have held for some time: the illness patterns since 2020 do not look normal. They do not look like a return to baseline respiratory medicine. They look altered.
The Immune System May Not Be Failing Equally
What I pressed Joachim on — and what I think is the real scientific issue — is whether we are seeing immune deficiency, or whether the immune system has become chronically dysregulated and is focusing on the wrong targets. An immune-deficient patient cannot mount the appropriate defence. A dysregulated patient may still have plenty of immune activity, but it is maladaptive, misdirected, or exhausted.
That matters because long COVID has always looked to me like more than one problem at once. There is inflammation. There is endothelial disturbance. There is abnormal innate activation in many patients. There are patterns suggesting ongoing immune stimulation. But there is also surveillance failure, viral reactivation, fungal issues, opportunistic patterns, and unusual clinical behaviour in conditions that previously followed a more predictable course. That is not the profile of a healthy immune system. But neither is it textbook immunodeficiency.
What makes this so difficult is that these processes coexist. You can have an immune system overactive in one compartment and ineffective in another. You can have inflammatory signalling, autoantibody generation, and poor viral control simultaneously. You can have a patient who looks inflamed yet behaves immunologically as if they are not handling secondary threats properly. That is why I keep returning to the idea of chronic immune dysregulation with selective loss of immunocompetence. It is messier, but more faithful to what we are actually seeing.
Thursday 16th April, 2026 at 7PM UK time
The Population Signals Are Hard to Ignore
Part of what gave this discussion weight is that it is no longer just about individual long COVID patients. What interests me now is the broader shift in disease presentation across the population. Joachim pointed to clinicians in Germany reporting more shingles, EBV reactivation, Candida, bacterial opportunists, and mycoplasma. He framed these as evidence of worsening immunocompetence. Whether every one of those links holds up under close epidemiological scrutiny is a separate question. But the larger signal is real: there are too many unusual patterns to dismiss them all as coincidence.
I made the point during the discussion that in UK metadata there appears to be a falloff in sepsis diagnosis, despite no obvious reason to believe serious infections have vanished. My reading is not that infection has disappeared, but that some patients may no longer be presenting in the usual way. Clinicians who work with immunocompromised patients understand this well. When the immune response is altered, the presentation becomes altered. That does not prove a specific mechanism, but it tells us the physiology may have shifted.
This is why the long COVID discussion cannot remain confined to fatigue, palpitations, and brain fog. Those matter. But they may only be part of a wider post-pandemic change in immunological behaviour.
Cancer Is Part of This Conversation
One area where I think people are still not being honest enough is cancer. I have no interest in slogans like “turbo cancer.” That language muddies the discussion and makes serious scientists switch off. But it is becoming increasingly difficult to deny that something about cancer presentation appears different.
What concerns me is not simply that cancers exist, but that some are behaving as if they are presenting later and spreading faster than we would normally expect. I used melanoma as an example because it is one of the clearest models we have for aggressive metastatic behaviour. What I am seeing — and what I suspect many others are quietly seeing — is that some ordinary cancers appear to be behaving more like that. By the time the patient turns up, the disease is already advanced.
I also raised the possibility that molecules like CD147 may be part of this story. If cancer cells are already in a state of altered receptor expression and then encounter persistent spike-related biology, the question is not whether that matters in theory. The question is how much it matters in practice. That is where the next stage of research needs to go — not into rhetoric, but into phenotype, receptor biology, immune surveillance, and altered cancer behaviour.
Why This Is So Difficult to Treat
The most uncomfortable part of this discussion is that even if we are right about the broad direction, that does not automatically give us a therapeutic answer.
Joachim made the point — and I agree — that if there is a strong autoimmune component in the post-viral phase, you cannot simply “boost” the immune system indiscriminately. That is naive medicine. If the immune system is dysregulated, ramping it up without precision may worsen the exact processes you are trying to control. It may intensify autoantibody production, inflammatory damage, or tissue injury.
This is why so much of the future lies in immune phenotyping. We need to know which arm of the immune system is exhausted, which is overactive, which is misdirected, and which patients sit in a state of persistent antigen burden versus autoimmune drift versus endothelial inflammation versus macrophage-driven chronic activation. Without that, treatment is guesswork.
And guesswork is not good enough anymore.
The Real Question Going Forward
What stayed with me after the discussion was not the phrase immune collapse. It was the realisation that we may still be using outdated language for a new biological reality.
There is evidence that many patients have lost some degree of immunocompetence. The rise in unusual infections, atypical patterns, and altered clinical presentation should concern us. But the more accurate description may be that we are dealing with a chronic maladaptive immune state: part inflammatory, part exhausted, part autoimmune, part surveillance failure. That is more complex than immune deficiency, but it is more honest.
If I had to put it simply: the immune system after COVID does not always look weak. It looks confused, overworked, badly directed, and in some patients increasingly unable to do the right job at the right time. That may be more dangerous still, because it hides behind normal counts, vague labels, and familiar language while the biology underneath continues to shift.
That is the conversation we should be having now. Not whether it is convenient or whether it fits the preferred narrative — but whether we are prepared to recognise that post-pandemic medicine may be dealing with a very different immune landscape than the one we trained in.
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