🌟 𝐍𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: 𝐭𝐡𝐞 𝐜𝐨𝐧𝐧𝐞𝐜𝐭𝐢𝐨𝐧 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐥 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐥𝐢𝐞𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐚𝐧 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞🌟 🌐 I am excited to share with you our latest paper entitled "𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐀𝐒𝐈𝐀: 𝐀 𝐯𝐚𝐜𝐜𝐢𝐧𝐞- 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐛𝐞𝐡𝐢𝐧𝐝 𝐭𝐡𝐞 𝐨𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬". In this paper, we explain the links between Long COVID, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME/CFS) and COVID-19 post-vaccine syndromes. 🤔 Stay reading to the end and you will also find our treatment proposal that could improve symptoms.💊 ➡️𝐋𝐢𝐧𝐤 𝐨𝐟 𝐨𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: frontiersin.org/journals/imm… 🔍 𝐀𝐛𝐬𝐭𝐫𝐚𝐜𝐭: We present a model for the development of these diseases that involves a complex interplay between immune hyperactivation, autoimmune hypophysitis or pituitary hypofunction, and immune exhaustion. We believe that the starting point is a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1). This would follow from an uncontrolled immune response with hyperactivation of CD8 T cells and elevated antibody production, some of which could be directed against self-antigens, triggering autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. 🧬 🔬 𝐖𝐡𝐚𝐭'𝐬 𝐭𝐡𝐞 𝐛𝐢𝐠 𝐝𝐞𝐚𝐥? 1️⃣ 𝐑𝐞𝐥𝐚𝐭𝐢𝐨𝐧𝐬𝐡𝐢𝐩 𝐭𝐨 𝐀𝐒𝐈𝐀 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞: We propose that Long COVID, ME/CFS and post-vaccine COVID-19 syndrome could be included in adjuvant-induced autoimmune/inflammatory syndrome (ASIA) due to their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. 2️⃣ 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭𝐚𝐥 𝐌𝐨𝐝𝐞𝐥: We suggest that these diseases begin with a deficient immune response and progress to uncontrolled immune hyperactivation, followed by immune exhaustion, exacerbating symptoms and pathology. 3️⃣ 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚: We highlight the decrease in ACTH production and its impact on immune function and clinical symptoms, establishing a direct link with pituitary dysfunction. 4️⃣ 𝐓𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐏𝐫𝐨𝐩𝐨𝐬𝐚𝐥: We propose a treatment approach including antivirals, corticosteroids/ginseng, antioxidants and metabolic precursors to improve symptoms by modulating immune response, pituitary function, inflammation and oxidative stress. 💡 𝐈𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧𝐬: 🔹These disorders could have an autoimmune origin against the adenohypophysis. 🔹Treatment with antivirals and corticosteroid replacement therapy in patients with permanent pituitary damage could improve symptoms by addressing immune and hormonal dysfunction. 🧠 𝐓𝐡𝐞 𝐤𝐞𝐲 𝐢𝐬 𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐝𝐚𝐦𝐚𝐠𝐞: 𝐡𝐨𝐰 𝐝𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐫𝐞𝐥𝐚𝐭𝐞 𝐭𝐨 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐌𝐄/𝐂𝐅𝐒, 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐨𝐭𝐡𝐞𝐫 𝐩𝐨𝐬𝐭-𝐯𝐢𝐫𝐚𝐥 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬? 💉 Certain viruses (and other pathogens) and vaccines can affect the pituitary gland, interfering with cortisol production and triggering a cascade of complex symptoms. In patients with weak HLA-DRB1 alleles, such as DR15, immune hyperactivation can trigger an autoimmune response against ACTH, crucial for cortisol production. This is exactly analogous to how other autoimmune diseases such as multiple sclerosis or lupus develop, where the immune system attacks other antigens in the body, but in the syndromes we are discussing, the autoimmunity is specifically directed against pituitary ACTH. 🦠 This link explains why patients with chronic infections often experience persistent hypocortisolemia, as the pathogen continues to produce ACTH-mimicking antigens, maintaining the active autoimmune response or generates direct pituitary damage. In contrast, patients without chronic infections and with the same weak alleles treated with immune checkpoint inhibitors (ICIs) may develop temporary hypophysitis and similar cortisol deficits, but discontinuation of treatment usually allows recovery. This also explains why patients experience chronic fatigue, dysautonomia, orthostatic intolerance, exercise intolerance, intolerance to stressful events and mild hypoglycemia due to low cortisol. Cortisol is crucial in providing the body with needed energy and regulating the stress response. When cortisol levels are low, as they are in these syndromes, the body cannot respond effectively to physical and emotional demands. 🩸Cortisol plays a crucial role in maintaining stable blood sugar levels by promoting gluconeogenesis (glucose production) and stimulating the release of stored glucose in the form of glycogen in the liver. When there is insufficient cortisol, the body faces difficulties in increasing glucose levels in demand situations, such as during physical exercise or in response to stress, which can lead to episodes of mild hypoglycemia. In times of fright or anger, adrenaline release may temporarily improve symptoms by temporarily increasing glucose availability, briefly compensating for cortisol deficiency. However, this response does not adequately replace the long-term regulatory functions of cortisol, so symptoms may return once adrenaline subsides. 🏋️‍♂️ In the case of physical exercise, which naturally increases cortisol levels to mobilize energy and respond to physical exertion, the lack of this hormone limits the body's ability to maintain sustained physical activity. Patients may experience rapid muscle fatigue, feelings of weakness and slower recovery after exercise. 😰 As for stressful events (exams, travel, surgical operations, etc) , cortisol also plays a crucial role in the body's response to emotional or physical stress. When cortisol levels are insufficient, the body has difficulty handling stressful situations effectively. This can manifest itself in an exacerbation of existing symptoms, such as intense fatigue, dizziness, difficulty concentrating and a generalized feeling of malaise. ➡️ For years, many of these patients have been misunderstood and mislabeled as having psychosomatic illness. This is because their symptoms tend to worsen during periods of stress, which has led to the suggestion that the origin of their problems lies in psychological factors. However, the reality is that these patients are not experiencing symptoms due to an underlying psychological disorder, but as a direct result of insufficient cortisol. The lack of this vital hormone prevents the body from adapting and responding appropriately to stress, which perpetuates and aggravates their physical symptoms. 🚨 𝐓𝐡𝐞 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐭𝐨 𝐀𝐂𝐓𝐇: 𝐀 𝐏𝐫𝐨𝐜𝐞𝐬𝐬 𝐒𝐢𝐦𝐢𝐥𝐚𝐫 𝐭𝐨 𝐎𝐭𝐡𝐞𝐫 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐃𝐢𝐬𝐞𝐚𝐬𝐞𝐬 𝐬𝐮𝐜𝐡 𝐚𝐬 𝐌𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐒𝐜𝐥𝐞𝐫𝐨𝐬𝐢𝐬 🚨 This same mechanism occurs in other autoimmune diseases. Some HLA-II alleles, such as the DR15 variant, are associated with an impaired ability to recognize cells infected with certain pathogens, such as Epstein-Barr virus (EBV). In multiple sclerosis this poor recognition ability specifically affects CD4 T cells, which are crucial for coordinating the immune response. When CD4 T cells cannot correctly recognize infected cells, this leads to hyperactivation of CD8 T cells and an increase in antibodies against the pathogen to compensate for the deficient CD4 T cell response. Without the coordinated help of CD4 T cells, CD8 T cells cannot eliminate all EBV-infected cells, thus never effectively eliminating or controlling the infection and resulting in chronic infection. This results in an increase of infected cells, an exhaustion of CD8 T cells and an increased risk of developing autoimmune diseases, since CD4 T cells, by misrecognizing these viral antigens presented on the HLA-II antigen-presenting cells, can confuse them with the body's own proteins, generating an autoimmune disease. In multiple sclerosis, autoimmunity develops when the EBNA-1 antigen of the Epstein-Barr virus is mistaken for myelin, due to a similar amino acid sequence and molecular mimicry in patients with DR15 alleles. The same could occur in patients with Long COVID, myalgic encephalomyelitis and post-vaccinal syndromes, where autoimmunity against ACTH develops. #LongCovid #MECFS #Vaccines

‼️⚠️I sincerely appreciate that you acknowledged this mistake. Recognizing errors publicly is not easy, and I respect that. But I also think this is why I have to ask you to look again at the much bigger issue: the WIRED article itself. Because the problem is not only one misread study. The broader framing of that article is already causing real harm. I say this sincerely: I know there is a person behind every account, with their own intentions, limits, mistakes and blind spots. We can all get things wrong. I do not believe the right response is to destroy someone when they are willing to correct mistakes. But the article needs correction. Over the last few days, I have received comments and private messages from patients saying that family members, people around them, and even clinicians who do not understand Long COVID are now using this narrative against them. They are being told that they are not recovering because they do not want to. Because they are not exercising. Because they are not doing psychological therapy. Because they are “stuck” in the wrong mindset. You may not fully realize the damage that kind of framing can do if you have not lived this disease closely. For many patients, their environment had finally started to believe them because biomedical research was moving forward. Years of studies showing immune, vascular, autonomic, metabolic and muscular abnormalities were slowly helping people understand that this is a real organic disease. And then a simple, attractive narrative appears again: maybe it is mind-body. maybe patients are afraid of exercise. maybe recovery is being blocked by beliefs. That kind of framing can erase years of progress in one family, one workplace, one clinic. Because when a disease is complex and poorly understood, the easiest story is always the old one: maybe the problem is psychological. ME/CFS patients have lived with this harm for decades. Many Long COVID patients are now experiencing the same thing. And this pressure is not harmless. Patients lose their health. They lose their jobs. They lose their social lives. They lose their independence. And then, when public narratives suggest that maybe they are not recovering because of their mindset, they can also lose the last thing they had left: being believed and supported. That pressure can become unbearable. Some patients end up taking their own lives because they feel abandoned, disbelieved and blamed for an illness they did not choose. Those lives matter. They matter as much as yours or mine. And these patients deserve exactly the same dignity, seriousness and protection that we give to patients with any other recognized disease. Today, nobody would tell a patient with multiple sclerosis that they remain ill because they do not want to recover, because they do not exercise enough, or because they have not done the right psychological therapy. Nobody would frame MS as a failure of mindset just because fatigue, stress sensitivity, cognitive symptoms or depression can appear in the disease. So why is this acceptable with Long COVID or ME/CFS? This is not about rejecting psychological support. It is not about denying that the nervous system is involved. It is not about saying every recovery story is false. It is about not confusing support with cure. Not confusing subjective improvement with disease modification. Not confusing heterogeneous biology with “it might be in your head.” Not using recovery anecdotes to reframe a post-infectious disease in a way that patients will pay for socially, medically and personally. I genuinely believe people can reconsider things. None of us has to know everything about every field. Mistakes happen. But when a mistake has consequences for a vulnerable patient community, correction matters. The same criticism I have made these days, I would gladly replace with support if you helped correct the framing and the harm caused by the article. Patients deserve mechanisms.

⚠️After seeing the response from patients, clinicians and scientists, I think this needs to be said clearly: Re-promoting an article that has caused so much harm to the Long COVID community is not brave journalism. It is irresponsible. This article did not simply “open a difficult conversation.” It amplified a deeply damaging frame: that maybe patients are rejecting the uncomfortable truth that CBT, exercise and “mind-body” approaches are the way forward. But when you present a complex post-infectious disease through that lens, without properly separating psychological support from biological treatment, you are not helping patients. You are making their lives harder. These narratives do not stay inside an article. They reach families. They reach employers. They reach disability assessors. They reach doctors who already know very little about Long COVID. They reach people who are looking for an excuse to say: “maybe it is just anxiety,” “maybe you are afraid of exercise,” “maybe you are keeping yourself sick.” That has consequences. Social consequences. Medical consequences. Workplace consequences. Psychological consequences. Patients with Long COVID are already fighting disbelief, lack of biomarkers in routine care, lack of approved treatments, disability, isolation and medical neglect. Using their suffering to generate clicks while repackaging old psychosomatic narratives in modern “mind-body” language is not courageous. It is cruel. The problem is not talking about the nervous system. The problem is turning nervous system involvement into a story about beliefs, fear, trauma or patients refusing to accept recovery. The problem is using recovery anecdotes as if they establish causality. The problem is ignoring those who worsened with exercise. The problem is presenting PEM caution as dogma. The problem is being much more generous with “brain retraining” narratives than with the biomedical evidence already showing immune, vascular, autonomic, metabolic and muscular abnormalities in Long COVID. If a journalist wants to write about Long COVID, they have a responsibility to understand the history of harm done to post-infectious patients. Because this is not new. ME/CFS patients have lived this for decades. “Unexplained” became “psychological.” “Normal routine tests” became “nothing is wrong.” “Supportive care” became “cure.” “Exercise” became “rehabilitation,” even when patients were crashing. And now the same mistake is being repeated with Long COVID. Patients are not angry because they reject science. They are angry because they recognize the pattern. They have seen what happens when medicine turns biology it cannot yet measure into psychology. So no, this is not “a way forward.” A way forward would be stratification, biomarkers, mechanistic trials, antivirals, immunology, dysautonomia research, PEM-safe protocols, autoantibody studies, vascular biology, tissue persistence, metabolism and serious clinical phenotyping. A way forward would be listening to all patients, including those harmed by exercise and psychologizing narratives. A way forward would be scientific humility: admitting what we still do not know without turning unexplained biology into psychology. Not click-driven repetition of the same ideas that have already harmed post-infectious patients for decades.

💊‼️Long COVID could be, at least in some patients, an autoimmune disease occurring alongside chronic infection, antigenic persistence, or viral reactivations. Okay. So now what? Are there treatments? Can autoantibodies be removed? Can this autoimmunity be “switched off”? Are we close to a cure? The honest answer is this: we are not facing an immediate cure , although possibly a future one, but we are facing a huge shift in how we think about the disease. Because if part of Long COVID, and possibly also ME/CFS, has an autoimmune basis, then it would no longer make sense to treat it as a diffuse syndrome with no therapeutic direction. We would need to do the same thing we do in other autoimmune diseases: classify patients properly, identify biomarkers, and design a stepwise treatment approach. Not all patients would have the same mechanism. Not all patients would respond in the same way. And not all patients would need the same level of treatment. But for the first time, a more logical therapeutic map is starting to emerge. A clearer logic is beginning to appear: identify which patients have a real autoimmune component and, from there, think about which therapies could make sense. At present, what is accessible would not be a cure, but treatments already known from other autoimmune diseases that could help reduce autoantibody activity, modulate the immune response, or decrease part of the immunological damage. In the best-case scenario, these would be treatments to improve, stabilize, or reduce autoimmunity. Not to completely “erase” the disease. If I had to rank the options in an orientative way, thinking about potential usefulness and safety profile, I would do it like this: 1. IVIG The most reasonable short-term option would probably be IVIG, meaning intravenous immunoglobulin. IVIG does not directly eliminate all autoantibodies as such, but it can modulate the immune system, compete with pathogenic autoantibodies, block part of the inflammation, and dampen the immunological attack without requiring such intense immunosuppression. In many autoimmune diseases, it is used precisely because of this immunomodulatory effect. Among this type of therapy, it is probably one of the options with the best balance between potential usefulness and safety profile. That said, it is not free of side effects, it is expensive, and access is limited. 2. FcRn inhibitors Next, I would place FcRn inhibitors. These drugs are very interesting because they reduce the total amount of circulating IgG and, with it, they can also reduce the burden of pathogenic autoantibodies. The advantage is that they are quite targeted toward the humoral component of autoimmunity, meaning the antibody-mediated part. The disadvantage is that they are not yet truly established for Long COVID or ME/CFS, and it would still be necessary to demonstrate very clearly which subgroup of patients would benefit the most. Even so, conceptually, if we are talking about an autoantibody-mediated disease, this is one of the most promising strategies. 3. Immunoadsorption At the next level, I would place immunoadsorption. This technique consists of filtering the blood to remove immunoglobulins, especially those that may be participating in the autoimmune process. It is a more targeted strategy than systemic immunosuppression and, in diseases mediated by autoantibodies, it can make a lot of sense. Its main limitation is logistical: it is not a simple therapy, it requires specialized centers, and its effects may not last if the immune system continues producing the same autoantibodies afterwards. (1/3) 🔵Continued in the next post.👇🏻

⚠️‼️ I came across this news in Spain, and this discourse keeps doing enormous harm. The post literally says: “A study from Hospital del Mar reveals a worrying connection between childhood trauma and physical diseases in adult life. From headaches to diabetes, adverse childhood experiences could leave marks on our health. Early prevention has never been so crucial.” “A study from Hospital del Mar details numerous physical diseases linked to childhood trauma.” Not because they literally said that most organic diseases are caused by childhood trauma, but because in practice, many of the diseases they attribute to or reduce to trauma end up being organic diseases whose biomarkers have not yet been discovered, or whose proper medical workup was never even done. And that is the real problem. For years, many patients are first filtered through the lens of trauma, psychosomatic illness, or somatization, when in reality what they have is an organic disease that has simply not yet been diagnosed. I would even go further and say that this also happens with diseases we now understand well: before reaching the right specialist and before the appropriate tests are performed, many patients are treated as if the origin of their symptoms were psychological or trauma-related, simply because nobody has investigated their case properly. That is not precision medicine. That is a way of covering diagnostic ignorance with a psychological narrative. The history of medicine shows this again and again: many diseases that in their early stages were treated as “nervous,” “hysterical,” or “psychosomatic” later turned out to be well-defined organic diseases. This happened with multiple autoimmune, neurological, and inflammatory diseases. And it is still happening today. That is why this discourse is so dangerous. Because it not only delays the real diagnosis, but also blames the patient, isolates them, sends them into the wrong clinical pathways, and steals years of serious medical investigation from them. Most of these patients do not need their illness to be explained through trauma. They need the right tests, the right specialist, and serious investigation of their real biology instead of convenient theories being projected onto them. Enough of turning the absence of known biomarkers into a psychological explanation. What some people today call trauma or somatization too often ends up tomorrow having a name, a mechanism, and a biological marker.

🔴 I think this is an important point, so I’ll add my perspective here. I have read the article carefully, and I explain the specific problems I see in this full thread. My criticism is not that those patients should not be believed. Of course they should be listened to. The problem is turning individual recovery stories into a broader framing that risks confusing psychological support with causal treatment, and nervous system modulation with a cure for Long COVID. Listening to patients who improved does not mean ignoring patients who worsened with exercise, PEM, dysautonomia, autoantibodies, viral reactivations, or objective abnormalities after exertion. Both groups matter. But testimonials do not establish causality, and they should not be used to reframe a heterogeneous post-infectious disease as something primarily driven by beliefs, fear, trauma, or “mind-body” loops. In this thread, I go point by point through what I think the article gets wrong. If after reading it you still disagree, I would genuinely be interested in hearing your arguments. 👉🏼 x.com/manruipa/status/206189…

⚠️ I think this is exactly the problem. When patients with ME/CFS, fibromyalgia or Long COVID defend themselves, it is often framed as “protecting an illness narrative.” But if your disease were constantly minimized, psychologized, ignored, and left without biological treatments, while patients are told they are exaggerating or inventing symptoms, this would not feel like protecting a narrative. It would feel like defending the basic right to be taken seriously and treated with the same dignity as patients with any other disease. These narratives do not only affect medical care. They affect families, friendships, work, disability support, and social isolation. Patients are not protecting illness. They are protecting themselves from being abandoned by a system that too often turns unexplained biology into psychology. I invite you to read the full thread, because I do not think this is a fair defense of the article: x.com/manruipa/status/206189…

(3/6)The article also presents “astonishing” recoveries as if they were evidence in favor of brain retraining. But this is scientifically weak too. In many post-infectious diseases, there is a window in which some patients improve over time. This happens after viral infections such as EBV. Some people have symptoms for months after mononucleosis and then recover. Others do not recover and develop persistent symptoms, autoimmunity, or post-infectious syndromes. If a person improves at 6, 9, or 12 months while doing a “brain retraining” program, that does not prove the program cured them. It may have coincided with natural recovery, pacing, rest, reduced workload, symptomatic treatment, beta-blockers, antihistamines, aspirin, LDN, antivirals, better sleep, less physical stress, fewer infections, or simply fluctuation of the disease. Testimonials matter. But they do not replace causality. And you cannot use patients who improve to invalidate patients who worsen with exercise. Another point from the article: “If exercise did indeed trigger post-exertional malaise in most patients, this level of caution would be warranted.” This approach is extremely dangerous. First, because post-exertional malaise does not always appear during exercise. Many times it appears 24, 48, or 72 hours later. If you perform a test in a controlled setting and only look at the immediate response, you may not be capturing the main problem. Second, because Long COVID is heterogeneous. The fact that one subgroup tolerates rehabilitation does not mean that another subgroup with PEM, POTS, or autonomic autoimmunity can tolerate it. Third, because there are already studies showing objective abnormalities after inducing PEM in Long COVID patients, including muscle abnormalities, metabolic alterations, and worsening muscle damage after exertion. That is why the cautious recommendation is not “everyone should exercise.” The cautious recommendation is: first stratify. Does the patient have PEM? Do they have POTS? Do they have dysautonomia? Do they have autonomic autoantibodies? Do they have muscle damage or metabolic intolerance to exertion? Are they in a flare? Are they mild, moderate, severe, or bedbound? Do they worsen 24–48 hours after physical or cognitive activity? Without answering that, recommending exercise globally is not personalized medicine. It is playing roulette with vulnerable patients. The sentence “not exercising increases the risk of cardiovascular disease, metabolic disease, diabetes, depression, or Alzheimer’s” is true in the general population. But using it to pressure patients with PEM is a bad extrapolation. We could also say that sunlight is necessary for vitamin D. But that does not mean you send someone with photosensitive lupus into the sun during a flare. We could also say that exposure to pollen is harmless for many people. But that does not mean you run a trial putting patients allergic to olive pollen in an olive grove to prove to them that nothing happens. We could also say that movement is healthy. But if a person with severe Long COVID worsens every time they exceed their limit, the scientific thing to do is to investigate why, not tell them they are deconditioned. When you have an acute flu, the doctor does not say: “go for a run, otherwise you will become deconditioned.” They say: rest, hydration, and caution. 🔵Continued in the next post.👇🏻

‼️That state can also be explained biologically. If some patients develop autoantibodies against muscarinic receptors such as M3, and possibly other autonomic targets, parasympathetic signaling may be impaired. In simple terms, the “brake” of the autonomic nervous system does not work properly, so the body can remain stuck for longer in a fight-or-flight state. That could help explain dysautonomic flares without needing to reduce everything to a purely psychological or abstract brain-loop model.