New: Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

[Manuel]

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 𝐭𝐨 𝐓𝐰𝐢𝐭𝐭𝐞𝐫/𝐗 𝐭𝐡𝐫𝐞𝐚𝐝 𝐞𝐱𝐩𝐥𝐚𝐢𝐧𝐢𝐧𝐠 𝐢𝐭: https://x.com/manruipa/status/1810664159354192253

𝐋𝐢𝐧𝐤 𝐨𝐟 𝐨𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

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?

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.

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.

𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚: We highlight the decrease in ACTH production and its impact on immune function and clinical symptoms, establishing a direct link with pituitary dysfunction.

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.

𝐖𝐡𝐲 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐂𝐚𝐧 𝐃𝐞𝐯𝐞𝐥𝐨𝐩 𝐏𝐚𝐭𝐡𝐨𝐥𝐨𝐠𝐢𝐞𝐬 𝐒𝐢𝐦𝐢𝐥𝐚𝐫 𝐭𝐨 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐏𝐨𝐬𝐭-𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐌𝐄/𝐂𝐅𝐒?

𝐂𝐨𝐦𝐦𝐨𝐧 𝐌𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦: 𝐔𝐧𝐜𝐨𝐧𝐭𝐫𝐨𝐥𝐥𝐞𝐝 𝐈𝐦𝐦𝐮𝐧𝐞 𝐀𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧.
Both persistent COVID and post-infectious ME/CFS and post-vaccine syndrome share a common basis: an overactive immune response. In our study, we propose the presence of:

𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐜𝐞 𝐨𝐟 𝐕𝐢𝐫𝐚𝐥 𝐀𝐧𝐭𝐢𝐠𝐞𝐧𝐬 𝐨𝐫 𝐀𝐝𝐣𝐮𝐯𝐚𝐧𝐭𝐬:
𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐯𝐢𝐫𝐚𝐥 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧: after a viral infection, such as SARS-CoV-2 or Epstein-Barr virus (EBV), viral antigens may remain in the body, triggering a continuous immune response.
𝐕𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧: Vaccines contain adjuvants designed to stimulate the immune system. In genetically predisposed individuals (HLA-DRB1), this stimulation may be excessive, leading to uncontrolled immune activation similar to a viral infection. In addition, the introduced viral antigens could have molecular mimicry with ACTH, exacerbating the immune response and potentially contributing to the development of autoimmunity against ACTH.


𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐀𝐠𝐚𝐢𝐧𝐬𝐭 𝐭𝐡𝐞 𝐀𝐝𝐞𝐧𝐨𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐬:
* Both conditions can lead to autoimmune inflammation of the adenohypophysis (autoimmune hypophysitis), resulting in hormonal dysfunction, especially ACTH production.


𝐇𝐲𝐩𝐞𝐫𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚 𝐚𝐧𝐝 𝐇𝐏𝐀 𝐀𝐱𝐢𝐬 𝐇𝐲𝐩𝐨𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧:
* Chronic inflammation and proinflammatory cytokine production can alter the hypothalamic-pituitary-adrenal (HPA) axis, leading to low cortisol levels, which exacerbate fatigue and other symptoms.

𝐂𝐲𝐜𝐥𝐞 𝐨𝐟 𝐇𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐈𝐦𝐦𝐮𝐧𝐞 𝐃𝐞𝐩𝐥𝐞𝐭𝐢𝐨𝐧:
𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐇𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧: Initial immune response is excessive, with high cytokine production and CD8 T-cell activation.

𝐈𝐦𝐦𝐮𝐧𝐞 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧: Over time, this hyperactivation leads to T-cell exhaustion, decreasing the body's ability to control infection and exacerbating the pathology.

𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦: Insufficient cortisol maintains the state of immune hyperactivation, perpetuating inflammation and hindering resolution of the immune cycle.

𝐄𝐯𝐢𝐝𝐞𝐧𝐜𝐞 𝐚𝐧𝐝 𝐂𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐒𝐢𝐦𝐢𝐥𝐚𝐫𝐢𝐭𝐢𝐞𝐬:
𝐒𝐡𝐚𝐫𝐞𝐝 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬: chronic fatigue, muscle and joint pain, sleep disturbances, cognitive problems, and post-exertional malaise.
𝐂𝐨𝐦𝐦𝐨𝐧 𝐆𝐞𝐧𝐞𝐭𝐢𝐜: Polymorphisms in the HLA-DRB1 gene predispose to an exaggerated immune response to both viral infections and vaccine components.

𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧: Our review suggests that both Long COVID and post-infectious ME/CFS and post-vaccination syndromes could be considered as part of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). These findings underline the need for a personalized therapeutic approach that takes into account the genetic predisposition and immune status of the patient.

𝐇𝐨𝐰 𝐂𝐚𝐧 𝐒𝐨𝐦𝐞 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐓𝐫𝐢𝐠𝐠𝐞𝐫 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐇𝐞𝐚𝐥𝐭𝐡 𝐏𝐫𝐨𝐛𝐥𝐞𝐦𝐬?
𝐌𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦 𝐨𝐟 𝐀𝐜𝐭𝐢𝐨𝐧:
Vaccines contain adjuvants and antigens designed to stimulate robust immune responses.
In some cases, this stimulation can lead to a dysregulated autoimmune response, similar to that seen in diseases such as systemic lupus erythematosus.

𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐈𝐧𝐯𝐨𝐥𝐯𝐞𝐝:
COVID-19: Cases of prolonged symptoms after infection or vaccination, known as Long COVID or post-COVID syndrome, have been reported.
Hepatitis B and C, HPV: Some individuals develop ME/CFS after vaccination, related to autoimmunity and immune alterations.

𝐑𝐢𝐬𝐤 𝐅𝐚𝐜𝐭𝐨𝐫𝐬:
Genetic predisposition such as polymorphisms in the HLA-DRB1 gene may increase susceptibility to abnormal immune responses.
Viral persistence or chronic antigen exposure may trigger a continuous and pathologic immune response.

𝐃𝐢𝐝 𝐲𝐨𝐮 𝐤𝐧𝐨𝐰 𝐭𝐡𝐚𝐭 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐝𝐞𝐬𝐢𝐠𝐧𝐞𝐝 𝐰𝐢𝐭𝐡 𝐚𝐝𝐞𝐧𝐨𝐯𝐢𝐫𝐮𝐬𝐞𝐬 𝐦𝐚𝐲 𝐡𝐚𝐯𝐞 𝐚 𝐬𝐥𝐢𝐠𝐡𝐭𝐥𝐲 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐫𝐢𝐬𝐤 𝐨𝐟 𝐭𝐫𝐢𝐠𝐠𝐞𝐫𝐢𝐧𝐠 𝐩𝐫𝐨𝐥𝐨𝐧𝐠𝐞𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞𝐬 𝐜𝐨𝐦𝐩𝐚𝐫𝐞𝐝 𝐭𝐨 𝐦𝐞𝐬𝐬𝐞𝐧𝐠𝐞𝐫 𝐑𝐍𝐀 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬?

Adenoviruses used as vectors may persist longer in the body, exposing the immune system to viral components for extended periods.

Adenoviruses are linear double-stranded DNA viruses and remain in an episomal condition in the nucleus. The mechanism of adenovirus vector persistence has not yet been elucidated. But they can persist for a long time in the organism. It is thought that it could be by their integration into the genome or by episomal gene duplication facilitated by the transcription machinery of the host cells. That is, it could happen that it transmits episomes to its cells as occurs in Epstein-Barr virus without lytic phase. During mitosis, EBV episomes are bound to chromosomes in metaphase through EBNA-1, allowing efficient segregation of episomes into daughter cells.

This theoretical phenomenon could predispose certain genetically susceptible individuals to develop chronic autoimmune or inflammatory disorders, as discussed in the context of ASIA syndrome. In contrast, messenger RNA vaccines, by rapidly degrading after inducing the desired immune response, limit this prolonged exposure.

Regardless of the type of vaccine against COVID-19 or other pathologies, whether messenger RNA or adenoviral vector, there is a theoretical possible risk of developing autoimmune disease only in individuals with certain genetic alleles, such as HLA-DRB1. The key lies in prolonged exposure to viral antigens, which could trigger persistent autoimmune responses.

mRNA vaccines are characterized by rapidly degrading after inducing the desired immune response, thus limiting prolonged exposure to viral components. In contrast, adenoviral vector-based vaccines can persist in the body longer, potentially increasing the risk of a longer-lasting autoimmune reaction in susceptible individuals.

It is crucial to remember that these risks are rare when compared to the total number of vaccinated individuals and that all vaccines, including adenovirus and messenger RNA vaccines, are critical to combat pandemic diseases such as COVID-19 at the species level. However, understanding these differences may help improve future vaccine design and surveillance for potential adverse effects in these susceptible individuals.

Recall that vaccines save millions of lives and prevent serious consequences of infections in the majority of the population. However, it is crucial to recognize that they may also present risks in some susceptible individuals.

HLA-DRB1 genetic alleles play a crucial role in predisposition to diseases such as Long COVID, myalgic encephalomyelitis (ME/CFS) and ASIA syndrome, as well as in post-vaccine syndromes.

These HLA-DRB1 alleles are part of the HLA (human leukocyte antigen) system, which regulates how the immune system recognizes and responds to foreign antigens, such as viruses and vaccine components. In individuals with certain HLA-DRB1 alleles, the immune system may trigger excessive or inappropriate responses to these antigens, leading to autoimmune conditions and inflammatory syndromes.

This explains why some patients, after significant viral infection or vaccination, may develop persistent autoimmune reactions. In the case of Long COVID and ME/CFS, persistence of viral antigens could trigger an autoimmune response against self tissues, including the pituitary gland.

In a 𝐤𝐞𝐲 𝐬𝐭𝐮𝐝𝐲, patients who developed hypophysitis after infection with the first SARS-CoV recovered their health months after treatment with replacement corticosteroids. This finding underscores the importance of detecting hypophysitis early to prevent permanent damage. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188349/

Hypophysitis can cause a decrease in ACTH production, crucial for adrenal function and immune response. Controlling ACTH levels is critical if symptoms such as chronic fatigue, orthostatic hypotension and sleep disturbances are present after a viral infection.

Early administration of replacement corticosteroids can stop ACTH secretion and prevent autoimmunity against this hormone, thus protecting the pituitary from further damage. Over time, as hypophysitis and viral infection subside, the dose of replacement corticosteroids can be gradually reduced until normal pituitary function is restored.

Challenges in HPA Axis Evaluation in Patients with Long COVID, ME/CFS and Post-Vaccine Syndromes.

Studies are often limited to single morning cortisol measurements, ignoring diurnal variability and cortisol response to physical/mental stress, which may underestimate problems in the HPA axis. In addition, CRH or ACTH stimulation tests, crucial for assessing pituitary and adrenal function, are not frequently performed.

It is crucial to detect HPA axis dysfunctions as early as possible to prevent adrenal atrophy due to low ACTH levels. Newly diagnosed patients may recover HPA axis function if autoimmune or direct damage by infection to the pituitary is detected early. Conversely, as time passes, the risk of pituitary damage from autoimmunity against ACTH increases, leading to further adrenal atrophy and the need for hydrocortisone replacement therapy. Early detection and treatment of these dysfunctions is crucial to improve the clinical management and quality of life of these patients.

𝐏𝐫𝐨𝐩𝐨𝐬𝐞𝐝 𝐀𝐜𝐭𝐢𝐨𝐧 𝐏𝐫𝐨𝐭𝐨𝐜𝐨𝐥 𝐟𝐨𝐫 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐜𝐚𝐬𝐞𝐬 𝐨𝐫 𝐨𝐯𝐞𝐫 𝟔 𝐦𝐨𝐧𝐭𝐡𝐬 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 𝐨𝐫 𝐏𝐨𝐬𝐭-𝐕𝐚𝐜𝐜𝐢𝐧𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐰𝐢𝐭𝐡 𝐏𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐃𝐚𝐦𝐚𝐠𝐞:
𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐨𝐧:
Laboratory and Imaging Tests: Pituitary MRI, Serum cortisol, saliva cortisol, 24h urine cortisol, plasma ACTH, DHEA-S and stimulation tests such as Synacthen test (synthetic ACTH stimulation test) to assess the status of the cortisol-producing adrenal glands. The diagnostic value of Synacthen lies in the assumption that chronic ACTH deficiency leads to adrenal atrophy and a consequent diminished response to stimulation with synthetic ACTH. A diagnosis of secondary adrenal insufficiency can also be confirmed with CRH stimulation testing.

𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭:
If presenting pituitary with decreased ACTH, initiate treatment with oral hydrocortisone to decrease the damage caused by autoimmunity to pituitary ACTH.

𝐅𝐨𝐥𝐥𝐨𝐰-𝐮𝐩:
-Perform cortisol and ACTH tests every 3 months during the first year .
-Repeat Synacthen stimulation tests to assess HPA axis recovery.

𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐇𝐏𝐀 𝐀𝐱𝐢𝐬 𝐑𝐞𝐜𝐨𝐯𝐞𝐫𝐲:
If post-stimulation cortisol is greater than 550 nmol/l:
-Consider gradually reducing the dose of hydrocortisone under medical supervision.
-Periodic post-suspension assessments to ensure that the HPA axis remains functional and that ACTH and cortisol levels remain at normal levels.

If post-stimulation cortisol is less than 550 nmol/l or there are symptoms when reducing hydrocortisone:
𝐇𝐲𝐝𝐫𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐧𝐞 𝐌𝐚𝐢𝐧𝐭𝐞𝐧𝐚𝐧𝐜𝐞:
Maintain hydrocortisone therapy at appropriate doses to control symptoms and avoid adrenal insufficiency.

𝐑𝐞𝐠𝐮𝐥𝐚𝐫 𝐌𝐨𝐧𝐢𝐭𝐨𝐫𝐢𝐧𝐠:
-Periodic cortisol and ACTH assessments.
-Adjust hydrocortisone dose based on test results and clinical presentation.
-Consider other hormonal treatments if deficiencies in other pituitary hormones are identified (e.g. thyroid consequences, DHEA).

𝐏𝐫𝐨𝐩𝐨𝐬𝐞𝐝 𝐀𝐜𝐭𝐢𝐨𝐧 𝐏𝐫𝐨𝐭𝐨𝐜𝐨𝐥 𝐟𝐨𝐫 𝐍𝐞𝐰 𝐂𝐚𝐬𝐞𝐬 𝐨𝐫 𝐥𝐞𝐬𝐬 𝐭𝐡𝐚𝐧 𝟔 𝐦𝐨𝐧𝐭𝐡𝐬 𝐨𝐥𝐝 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 𝐨𝐫 𝐏𝐨𝐬𝐭-𝐕𝐚𝐜𝐜𝐢𝐧𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐰𝐢𝐭𝐡 𝐏𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐃𝐚𝐦𝐚𝐠𝐞:

𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐨𝐧:
Laboratory and Imaging Tests: Pituitary MRI, Serum cortisol, saliva cortisol, 24h urine cortisol, plasma ACTH, DHEA-S and stimulation tests such as Synacthen test. ACTH testing may not be accurate in these patients when they present with secondary adrenal insufficiency for a shorter period because their adrenal glands have not yet shrunk and may still respond to ACTH. In such situations, CRH stimulation tests may be more appropriate, as they assess the ability of the pituitary to secrete ACTH. A low or absent ACTH response on CRH testing would indicate a problem at the pituitary level.

𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭:
If presenting pituitary with decreased ACTH, initiate treatment with oral hydrocortisone to decrease the damage caused by autoimmunity to pituitary ACTH.

𝐅𝐨𝐥𝐥𝐨𝐰-𝐮𝐩:
-Perform cortisol and ACTH tests every 3 months during the first year .
-Repeat stimulation tests to assess HPA axis recovery.

𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐇𝐏𝐀 𝐀𝐱𝐢𝐬 𝐑𝐞𝐜𝐨𝐯𝐞𝐫𝐲:
If post-stimulation ACTH is in normal ranges:
-Consider gradually reducing the dose of hydrocortisone under medical supervision.
-Periodic post-suspension assessments to ensure that the HPA axis remains functional and that ACTH and cortisol levels remain at normal levels.

If post-stimulation cortisol is below normal levels or there are symptoms when reducing hydrocortisone:
𝐇𝐲𝐝𝐫𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐧𝐞 𝐌𝐚𝐢𝐧𝐭𝐞𝐧𝐚𝐧𝐜𝐞:
Maintain hydrocortisone therapy at appropriate doses to control symptoms and avoid adrenal insufficiency.

𝐑𝐞𝐠𝐮𝐥𝐚𝐫 𝐌𝐨𝐧𝐢𝐭𝐨𝐫𝐢𝐧𝐠:
-Periodic cortisol and ACTH assessments.
-Adjust hydrocortisone dose based on test results and clinical presentation.
-Consider other hormonal treatments if deficiencies in other pituitary hormones are identified (e.g. thyroid consequences, DHEA

𝐓𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐏𝐫𝐨𝐩𝐨𝐬𝐚𝐥𝐬 𝐏𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐂𝐎𝐕𝐈𝐃, 𝐋𝐨𝐧𝐠-𝐄𝐯𝐨𝐥𝐮𝐭𝐢𝐨𝐧 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐏𝐨𝐬𝐭-𝐕𝐚𝐜𝐜𝐢𝐧𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐰𝐢𝐭𝐡 𝐏𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐃𝐚𝐦𝐚𝐠𝐞:

𝐂𝐨𝐫𝐭𝐢𝐜𝐨𝐬𝐭𝐞𝐫𝐨𝐢𝐝𝐬/𝐊𝐨𝐫𝐞𝐚𝐧 𝐫𝐞𝐝 𝐠𝐢𝐧𝐬𝐞𝐧𝐠:
How Do They Help? May reduce inflammation and regulate immune response. Reduces NF-kB pathway by decreasing oxidative stress and antioxidant intake. Corticosteroids in replacement doses are useful in cases of permanent pituitary damage, while ginseng may be beneficial in the long term by decreasing the production of proinflammatory cytokines and improving immune and adrenal function in cases with HPA axis disruption.

Important: In cases where mildly low cortisol levels are present, ginseng treatment alone could be started to assess whether cortisol levels increase naturally. If no improvement is observed, consider starting replacement doses with hydrocortisone, always under medical supervision.

𝐀𝐧𝐭𝐢𝐯𝐢𝐫𝐚𝐥𝐬: How Do They Help? Crucial in suppressing persistent viral replication, thus mitigating immune hyperactivity. Valtrex for herpesviruses such as EBV and Paxlovid for SARS-CoV-2.

𝐃𝐇𝐄𝐀 𝐬𝐮𝐩𝐩𝐥𝐞𝐦𝐞𝐧𝐭𝐚𝐭𝐢𝐨𝐧 𝐢𝐟 𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐞𝐱𝐢𝐬𝐭𝐬:
How Does It Help? DHEA is important for hormonal balance, especially when corticosteroid use inhibits ACTH production. It helps maintain energy and decrease the autoreactive T-cell response.

𝐀𝐧𝐭𝐢𝐨𝐱𝐢𝐝𝐚𝐧𝐭𝐬 𝐚𝐧𝐝 𝐌𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐜 𝐏𝐫𝐞𝐜𝐮𝐫𝐬𝐨𝐫𝐬:
Vitamins (C, B-complex), NAC, ALA, SAM-e, Selenium:
* How do they help? Reduce oxidative stress, improve mitochondrial function and restore glutathione levels, thus supporting cellular recovery and immune function.
NMN (Nicotinamide Mononucleotide):
* How does it help? Restores NAD+ levels, crucial for antiviral activities and cellular health.

𝐆𝐥𝐮𝐭𝐚𝐦𝐢𝐧𝐞:
* How Does It Help. Supports energy metabolism and immune function, especially during states of high immune demand.

𝐀𝐬𝐭𝐫𝐚𝐠𝐚𝐥𝐮𝐬:
* How Does It Help? Reduces oxidative stress and has immunomodulatory properties that may enhance CD4 T-cell deficient immune response and prevent viral reactivation, especially of EBV. Astragalus has shown indications of reducing clotting, which could have potential benefits in conditions associated with microclot formation.

𝐏𝐫𝐨𝐭𝐞𝐢𝐧 𝐚𝐧𝐝 𝐂𝐫𝐞𝐚𝐭𝐢𝐧𝐞 𝐬𝐮𝐩𝐩𝐥𝐞𝐦𝐞𝐧𝐭𝐚𝐭𝐢𝐨𝐧:
* How Do They Help? They maintain protein synthesis and prevent muscle breakdown, thus improving energy and physical recovery. Beware of creatine and protein supplements, as they do not suit everyone equally well, and may generate gastrointestinal problems.

𝐕𝐢𝐭𝐚𝐦𝐢𝐧 𝐃:
* How Does it help? Reduces T-cell hyperactivation and improves insulin sensitivity, which may have additional benefits in inflammatory diseases and insulin resistance.

𝐌𝐞𝐥𝐚𝐭𝐨𝐧𝐢𝐧:
* How Does It Help? Improves sleep, protects the central nervous system and reduces neuroinflammation and oxidative stress. It is essential not to sleep less than 8 hours, as in patients with hypocortisolism, lack of sleep can further destabilize cortisol production, worsen symptoms, destabilize circadian rhythms and reduce cortisol needed for awakening.

𝐀𝐧𝐭𝐢𝐡𝐢𝐬𝐭𝐚𝐦𝐢𝐧𝐞𝐬:
* How Do They Help? They reduce inflammation caused by histamine accumulation due to decreased DAO activity, decreasing Th2 response and improving allergies, food intolerances and fatigue.

𝐅𝐨𝐨𝐝:
* How Do They Help? These patients may tolerate less food and present food intolerances due to inflammation and oxidative stress, as a consequence of immune hyperactivation and low cortisol. The intestine is one of the tissues most affected by oxidative stress, especially during digestion, as this process generates free radicals that can damage intestinal cells. A diet rich in antioxidants is essential to neutralize these free radicals, mitigate tissue damage and improve food tolerance. It is therefore important to take antioxidant supplements during meals and avoid foods that generate more inflammatory load, such as those rich in histamine.

More information in our review article: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

𝐃𝐨𝐬𝐚𝐠𝐞 𝐚𝐧𝐝 𝐭𝐢𝐦𝐢𝐧𝐠 𝐨𝐟 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭𝐬
While many of these supplements may be familiar to most patients and some have even been tried before, the real key to this therapeutic approach lies in the precision of dosages and frequency of administration throughout the day to maintain stable blood levels. It is also critical to make these adjustments under proper medical supervision to ensure the long-term safety and efficacy of the treatment.


𝐄𝐱𝐩𝐞𝐜𝐭𝐞𝐝 𝐁𝐞𝐧𝐞𝐟𝐢𝐭𝐬:
Reduction of Inflammation and Oxidative Stress: Improving quality of life and daily energy.
Immune and Hormonal Regulation: Helping to stabilize immune and hormonal function.
Improving Clinical Symptoms: By addressing the root cause of immune and hormonal dysfunction, symptoms such as fatigue, pain and cognitive issues may decreas

To advance the scientific validation of these protocols, we are considering the possibility of conducting a clinical trial. We are currently seeking funding for this project, as we believe it is essential to demonstrate the efficacy of these treatments in a broader context. I also believe that, in order to advance as quickly as possible in the treatment of these pathologies, the collaboration of several centers testing these treatments is necessary. For that reason if any center/institution wants to do a joint study we are open to collaborate and receive funding.

Please, if you are taking these supplements and treatments and you are going to participate in any study of these diseases, I encourage you to communicate it to the responsible of the study. As they could change the results of the study. This is crucial to ensure the validity of the data and to avoid any bias that may mask the reality of these complex medical conditions. In addition, it is critical that these treatments and supplements be supervised by your physician.

Let's keep working together to advance the treatment of Long COVID, ME/CFS and post-vaccine syndromes! Thanks for reading this great thread!

𝐒𝐡𝐚𝐫𝐞 all this information with other patients and physicians/researchers to improve the quality of life for these patients. Together we can move towards more effective treatments and a better understanding of these medical conditions.

I will be uploading more information related to this article in the coming weeks.

Attached is another thread where we explain the consequences and development of acquired immunodeficiency in these patients:

This article has been possible thanks to the research line funded by @PlzSolveCFS and Helpify, carried out at the @CIMA_unav of the @unav with the team of Dr. Bruno Paiva (@BrunoPaiva_UNAV). we deeply appreciate their support!

 

[cfs since 1998]

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 𝐭𝐨 𝐓𝐰𝐢𝐭𝐭𝐞𝐫/𝐗 𝐭𝐡𝐫𝐞𝐚𝐝 𝐞𝐱𝐩𝐥𝐚𝐢𝐧𝐢𝐧𝐠 𝐢𝐭: https://x.com/manruipa/status/1810664159354192253

𝐋𝐢𝐧𝐤 𝐨𝐟 𝐨𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

Thank you, Manuel. It will take a few days for me to digest this but hopefully you will be back to answer questions.

 

[Wishful]

Am I not seeing any actual testing of this theory? I see lots of "theory suggests" and "theory x supports theory y", but no real "clinical measurements of z supports the theory". As for treatments, I'm pretty sure that plenty of people have tried ginseng and DHEA and various forms of cortisol ... with no reliable benefits.

The collection of individual theories in the paper offers possibilities to test, which is a good thing, but without supporting successful testing of the theory, it seems a bit early for "exciting announcement!!!" Cold fusion anyone?

 

[civicko]

@SWAlexander relevant to your comment posted in thread 'Herpesviruses, Endothelial Dysfunction, and ME/CFS' https://forums.phoenixrising.me/thr...ial-dysfunction-and-me-cfs.92130/post-2462713

wastwater, thanks.
He mentioned the dexamethasone test, which measures cortisol and ACTH levels. I have been advocating for cortisol and ACTH testing since 2021. Gradually, some doctors are beginning to understand its importance. However, the ACTH test is rare in Germany, as most endocrinologists have lost patience with insurance companies, meaning it often requires out-of-pocket payment. Unfortunately, he also promotes vaccination.

 

[beatsmyth]

I had my messages with sourced links and warnings about this community taking any mRna shots, deleted by the M0ds here. Know directly over 6 people who now have CFS/Fibro/Long Covid issues post vaxx and another handful in their 30's and 40's no longer with us and finally articles in Australia, Europe, and Japan are starting to come out showing that there indeed connections. I feel so sad for those of you took the shots.

 

[Hip]

I had my messages with sourced links and warnings about this community taking any mRna shots, deleted by the M0ds here. Know directly over 6 people who now have CFS/Fibro/Long Covid issues post vaxx and another handful in their 30's and 40's no longer with us and finally articles in Australia, Europe, and Japan are starting to come out showing that there indeed connections. I feel so sad for those of you took the shots.

That's a rather myopic and polarised view. I know 4 people in my social circle who died of COVID because they were unvaccinated. Cleary there are pros and cons to vaccination, and a balanced view would encompass all the nuances and situations.

It's not surprising that COVID vaccines can occasionally trigger ME/CFS, as many other vaccines are also known to do this. According to some pre-pandemic research by Dr Chia, around 1.5% of ME/CFS patients have their illness triggered by a vaccine.

Why a viral infection as well as a vaccination can trigger ME/CFS remains a mystery. If the dots can be connected between these two triggers, it should throw light on the nature of ME/CFS.

 

[beatsmyth]

That's a rather myopic and polarised view. I know 4 people in my social circle who died of COVID because they were unvaccinated. Cleary there are pros and cons to vaccination, and a balanced view would encompass all the nuances and situations.

It's not surprising that COVID vaccines can occasionally trigger ME/CFS, as many other vaccines are also known to do this. According to some pre-pandemic research by Dr Chia, around 1.5% of ME/CFS patients have their illness triggered by a vaccine.

Why a viral infection as well as a vaccination can trigger ME/CFS remains a mystery. If the dots can be connected between these two triggers, it should throw light on the nature of ME/CFS.

Well yes, people died from Covid as do a ton of people annually and globally from the Flu as well, When I had Covid, I couldnt breath for 3 days and thought I was a gonner, but luckily made it. However, after dealing with this CFS/Fibro illness for 20+ years and going through 30+ incompetent Doctors who have no business whatsoever even being Doctors, one can quickly learn and should learn and realize that you cant ever fully trust the Government, Big Pharma and its lawsuits, and the Big Medical industry. Look at all the commercials on TV, "Did you used to take such and such medications? Which you were told are safe, but in the end werent, and now have such and such issues from? Call now to join our class action lawsuits" I can post like 4o different examples from Big Pharma rolling out meds that were never safe and then killing people and having to pay fines in the Billions of dollars. I can also post studies of all the animals used in mRna vaccine tests dying from those tests and not a single one ever made it. And I can post studies, articles, Senators, Lawyers, Academics all discussing "Big Tech Censorship" that arose during the roll out of these shots.

I will say, I thank God I am pure blooded and never got a single Covid Vaccine, and I really seriously feel bad for those of you who did. And I have well over 200 Studies saved from all over the world now that will break your heart about these shots. But in the end, there's nothing I can do about it except watch my friends who did, one by one, continue to get sick and to pass away, and those who havent yet, refuse to look at my studies or believe I even have them. It's sad that I have front row seats to all of this

 

[Violeta]

Does anyone here have polymorphisms in the HLA-DRB1 gene?

And the COVID vaccine spoken of in the article is the one with the adenovirus adjuvant, not mRNA.

 

[Violeta]

Thank you, @Manuel, for the study, and for bringing it here to Phoenix Rising.

The chart is absolutely amazing.

Thank you for including in your study recommended tests and remedies.

It represents a lot of study, that is for sure. I am glad you are well enough to research ME/CFS for us.

 

[mattie]

Thanks for interesting post @Manuel ;
If I may ask: To what extent have you personally tried the proposed treatment options? And to what degree have you experienced improvement from them?

 

[Violeta]

Manuel's paper states that astragalus:

Reduces oxidative stress and has immunomodulatory properties that may enhance CD4 T-cell deficient immune response and prevent viral reactivation, especially of EBV. Astragalus has shown indications of reducing clotting, which could have potential benefits in conditions associated with microclot formation.

As stated in a paper by Vipin Vashitshtha on Twitter: In about 5% of anti-NMDAR patients, a brain inflammation caused by a herpes simplex infection later turns into autoimmune encephalitis; researchers think neurons destroyed by the virus release molecules that prompt the production of autoantibodies.

Here's a paper about astragalus and it's effect on that condition:

Identifying the Anti-inflammatory Effects of Astragalus Polysaccharides in Anti-N-Methyl-D-Aspartate Receptor Encephalitis​

https://www.ingentaconnect.com/content/ben/cchts/2024/00000027/00000007/art00008

Here is Vipin Vishitshtha's information if you would like to look for him on Twitter.

 

[Manuel]

Thanks for interesting post @Manuel ;
If I may ask: To what extent have you personally tried the proposed treatment options? And to what degree have you experienced improvement from them?

My Personal Experience with this Treatment Protocol:

Before starting this therapeutic approach, I was limited in my daily and academic capacity due to ME/CFS. I was unable to leave the house much, with orthostatic intolerance, constant dizziness, fatigue, bowel problems, dysutonmia, etc. However, since starting this protocol, I have been able to return to college to finish my studies, return to the gym and regain my physical strength through anaerobic exercise with weights. In addition, I have been able to reintroduce foods that previously caused me problems due to food intolerances I developed with ME/CFS. I even relapsed after a new SARS-CoV-2 infection but was able to return to my "improved" state again by following the protocol.

In my particular case, the introduction of antivirals, antihistamines, ginseng, astragalus, NAC and metabolic precursors has played a crucial role in improving my cortisol levels and immune markers. I want to make it clear that this is a symptomatic treatment and not a cure since antivirals against herpesviruses do not eliminate the latency cells of this virus. In addition, I am not yet fully healthy, I have some limitations and so I consider the possibility of permanent damage with hypofunction of my pituitary gland. Still, this protocol has made a significant difference in my quality of life. The next step I am considering is to introduce hydrocortisone in replacement doses. But first I have to be sure of permanent and irreversible damage to my pituitary.

However, it is important to note that I have only followed this protocol myself. To advance the scientific validation of these results, I am considering the possibility of conducting a clinical trial. We are currently seeking funding for this project, as we believe it is critical to demonstrate the efficacy of these treatments in a broader context. I also believe that, in order to advance as quickly as possible in the treatment of these pathologies, the collaboration of several centers testing these treatments is necessary. For that reason if any center/institution wants to do a joint study we are open to collaborate and receive funding.

 

[civicko]

Being HLA-DR15 negative directly exclude you from this model?

 

[Manuel]

Being HLA-DR15 negative directly exclude you from this model?

No. We believe that the main haplotypes that could be related to these diseases are the ancestral haplotypes DR2(DR15)-DQ6, DR3-DQ2 and DR4-DQ8.

There may also be other specific weak alleles against these antigens that we have not found.

In addition, the model may also be useful with only pituitary damage due to autoimmunity developed after infection or vaccination.

 

[civicko]

My Personal Experience with this Treatment Protocol:

Before starting this therapeutic approach, I was limited in my daily and academic capacity due to ME/CFS. I was unable to leave the house much, with orthostatic intolerance, constant dizziness, fatigue, bowel problems, dysutonmia, etc. However, since starting this protocol, I have been able to return to college to finish my studies, return to the gym and regain my physical strength through anaerobic exercise with weights. In addition, I have been able to reintroduce foods that previously caused me problems due to food intolerances I developed with ME/CFS. I even relapsed after a new SARS-CoV-2 infection but was able to return to my "improved" state again by following the protocol.

In my particular case, the introduction of antivirals, antihistamines, ginseng, astragalus, NAC and metabolic precursors has played a crucial role in improving my cortisol levels and immune markers. I want to make it clear that this is a symptomatic treatment and not a cure since antivirals against herpesviruses do not eliminate the latency cells of this virus. In addition, I am not yet fully healthy, I have some limitations and so I consider the possibility of permanent damage with hypofunction of my pituitary gland. Still, this protocol has made a significant difference in my quality of life. The next step I am considering is to introduce hydrocortisone in replacement doses. But first I have to be sure of permanent and irreversible damage to my pituitary.

However, it is important to note that I have only followed this protocol myself. To advance the scientific validation of these results, I am considering the possibility of conducting a clinical trial. We are currently seeking funding for this project, as we believe it is critical to demonstrate the efficacy of these treatments in a broader context. I also believe that, in order to advance as quickly as possible in the treatment of these pathologies, the collaboration of several centers testing these treatments is necessary. For that reason if any center/institution wants to do a joint study we are open to collaborate and receive funding.

So you had such recover without corticosteroids?

What would you say was the most helpful part of the protocol?

What metabolic precursors did you use? L-glutamine on it's own gave me a huge energy boost but in exchange of excitotoxcicity (insomnia, headaches, worst intolerances...) so had to stop taking it with a fatigue/brain fog rebound.

 

[SWAlexander]

In my particular case, the introduction of antivirals, antihistamines, ginseng, astragalus, NAC and metabolic precursors has played a crucial role in improving my cortisol levels and immune markers. I want to make it clear that this is a symptomatic treatment and not a cure since antivirals against herpesviruses do not eliminate the latency cells of this virus.

I'm pleased you've addressed the topic of cortisol and antihistamines. For over three years, I've advocated for cortisol/ACTH tests, often encountering resistance or dismissive attitudes. However, progress has been made among those willing to listen.

A nurse suffering from severe ME/CFS after C-19 infection listened to my advice and her cortisol test revealed alarmingly low levels. For some of my male friends, while their TSH levels were normal, a nuclear scan revealed dark spots on their thyroids and low cortisol levels, though their pituitary glands were unaffected.

I've also known a woman for years whom I suspected had Cushing’s syndrome. Her cortisol tests confirmed that her levels were excessively high. Additionally, another male acquaintance who experienced significant weight loss, muscle weakness, and high blood pressure finally underwent a catecholamine test. The diagnosis? High aldosterone and low potassium levels.

When I discussed my Addison's disease diagnosis from the US with my primary care provider in Germany, mentioning the need for frequent cortisol tests to adjust hydrocortisone doses or possibly switching to prednisolone, they seemed perplexed.

I've found that primary care doctors often do not order cortisol tests or thyroid ultrasounds due to insufficient knowledge, which unfortunately results in these tests being dismissed as unimportant. There is an urgent need for enhanced education among medical professionals regarding the function of hormons.

Besides, as someone with a compromised immune system due to Lupus, I am unable to take any NSAID or sulfa-based medications.

 

[ruben]

Does anyone know then if in UK we can simply go to our GP and request a cortisol test?

 

[SWAlexander]

ruben​

I'm not sure. ​

May I suggest you contact your GP and ask for a Cortisol test?
I know only an endocrinologist or a lab will perform the ACTH test.

If you are interested in more details, I wrote about a case report.

Aldosteronism (Conn's Syndrome) Cortisol and ACTH
https://swaresearch.blogspot.com/2024/06/comprehensive-guide-to-treatment-of.html​

 

[Manuel]

𝐖𝐡𝐲 𝐢𝐬 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐭𝐫𝐢𝐠𝐠𝐞𝐫𝐞𝐝 𝐛𝐲 𝐯𝐢𝐫𝐚𝐥 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 𝐭𝐡𝐞 𝐦𝐨𝐬𝐭 𝐥𝐢𝐤𝐞𝐥𝐲 𝐜𝐚𝐮𝐬𝐞 𝐨𝐟 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐏𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐥 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬?

New articles published this July support our hypothesis:


𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐩𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞𝐬.
Elevation of cytokines such as IL-6 leading to muscle deterioration
https://www.science.org/doi/10.1126/sciimmunol.adm7908

𝐎𝐮𝐫 𝐦𝐨𝐝𝐞𝐥: elevated IL-6, caused by poor control of infected cells and viral reservoirs, contributes to muscle deterioration.

Increased IFN-γ is linked to symptoms in Long COVID, and its reduction with IFN-γ inhibitors improves symptoms.
https://www.science.org/doi/10.1126/scitranslmed.adn0136

𝐎𝐮𝐫 𝐦𝐨𝐝𝐞𝐥: Interferon gamma (IFN-γ) is a proinflammatory cytokine that increases during chronic infections. Normally, cortisol controls IFN-γ levels. A decrease or dysregulation of cortisol can keep IFN-γ levels chronically elevated. If autoimmune hypophysitis is present, caused by infection or vaccine viral antigen, cortisol levels will be reduced, allowing continued T-cell activation and a persistent increase in IFN-γ. Thus, chronic inflammation and constant activation of the immune system, caused by persistent elevated levels of IFN-γ, can promote reactivation of latent viruses and an increase in infected cells. For example, IFN-γ increases the expression of MHC-II, facilitating the binding of Epstein-Barr virus to this receptor and its entry into cells. The improvement of symptoms with IFN-γ inhibitors suggests that restoring cortisol levels could alleviate symptoms, indicating a possible dysregulation of cortisol due to autoimmunity against the pituitary gland.

𝐕𝐢𝐫𝐚𝐥 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐜𝐞.
The continued presence of viral reservoirs in the mucous membranes and the increase of activated T cells in those same areas indicate continued reaction to infection and a subsequent exhaustion of T cells in blood.
https://www.science.org/doi/10.1126/scitranslmed.adk3295

𝐎𝐮𝐫 𝐦𝐨𝐝𝐞𝐥: this increase in activated T cells may lead to the development of autoimmune diseases, such as hypophysitis in genetically susceptible patients, similar to the risk in immune checkpoint inhibitor (ICI) patients with susceptible HLA-II alleles.

𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲.
Patients with #LongCOVID have autoantibodies against neural tissues, correlated with neurological symptoms. Transfer of these antibodies to mice induces similar symptoms.
https://www.medrxiv.org/content/10.1101/2024.06.18.24309100v1

The authors propose treatments based on therapies used in other autoimmune diseases.

* Intravenous immunoglobulin (IVIg): neutralizes and eliminates autoantibodies.
* FcRn inhibitors: Degrade antibodies by blocking their interaction with the neonatal Fc receptor.
* BC 007: Neutralizes autoantibodies against β1, β2, and M2 adrenergic receptors.
* Plasmapheresis: Temporarily removes antibodies from blood plasma.
* Anti-CD20 or CAR-T monoclonal antibodies: Attack and destroy antibody-producing B cells.

𝐎𝐮𝐫 𝐦𝐨𝐝𝐞𝐥: genetically predisposed patients (HLA-II alleles) may develop autoimmunity against various tissues, including the pituitary gland. If such autoimmunity is not treated in time, it can lead to irreversible damage.

Current treatments for autoimmune diseases can be effective in temporarily reducing or eliminating autoantibodies and controlling symptoms. However, these approaches have important limitations: they only address the effects of autoimmunity without eliminating the underlying cause, such as a persistent viral infection. If the viral antigen responsible for the autoimmunity is still present, autoantibody production can resume, reactivating the disease. CAR-T therapy shows promising potential, as it could eliminate autoantibody-producing B cells and, in the future, infected cells.

However, it should be crucial to combine these treatments with antivirals to reduce the viral load and the production of viral antigens that can induce molecular mimicry with self antigens. This could help to decrease the underlying autoimmune stimulus and improve disease control.

In addition, if treatment of autoimmunity is delayed and has caused damage to the pituitary gland, symptoms may persist due to irreparable damage to this organ, despite efforts to control autoimmunity. For that reason, some patients treated with these therapies may continue to have symptoms by having, for example, irreparable damage to the pituitary gland with cortisol depletion. In this case, treatment with hydrocortisone in replacement doses should be added.

𝐃𝐨 𝐲𝐨𝐮 𝐰𝐚𝐧𝐭 𝐭𝐨 𝐤𝐧𝐨𝐰 𝐦𝐨𝐫𝐞 𝐚𝐛𝐨𝐮𝐭 𝐡𝐨𝐰 𝐭𝐡𝐢𝐬 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐬 𝐚𝐧𝐝 𝐰𝐡𝐚𝐭 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭𝐬 𝐜𝐨𝐮𝐥𝐝 𝐢𝐦𝐩𝐫𝐨𝐯𝐞 𝐬𝐲𝐦𝐩𝐭𝐨𝐦𝐬?
Read this thread about our review article:
https://x.com/manruipa/status/1810664159354192253


𝐒𝐡𝐚𝐫𝐞 this information with your doctors and other patients to explore treatment options! Together we can work towards a better quality of life.

 

[Manuel]

So you had such recover without corticosteroids?

What would you say was the most helpful part of the protocol?

What metabolic precursors did you use? L-glutamine on it's own gave me a huge energy boost but in exchange of excitotoxcicity (insomnia, headaches, worst intolerances...) so had to stop taking it with a fatigue/brain fog rebound.

I have not yet introduced replacement doses of hydrocortisone because I wanted to see if the damage to my ACTH secretion was irreparable. I am not fully recovered with these treatments but I can do anaerobic exercise, study, go outside and have an almost normal life (but with some limitations). I still have some symptoms in the mornings and improve throughout the day with the treatments.
All these treatments influence and help the deficiencies caused by the infection so they should be combined. The ones I noticed the most in my symptomatic improvement were the antivirals, antihistamines, astragalus, NAC and ginseng. The important thing is the doses and to maintain as much as possible the stable levels in the blood.