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

[Manuel]

𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐧𝐠 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐌𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬: 𝐓𝐡𝐞 𝐑𝐨𝐥𝐞 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐂𝐞𝐥𝐥𝐬 𝐢𝐧 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬

Did you know that syndromes such as 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 and 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 share a common immune mechanism?


𝐂𝐨𝐧𝐭𝐢𝐧𝐮𝐨𝐮𝐬 𝐂𝐃𝟖 𝐓 𝐂𝐞𝐥𝐥 𝐀𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧:
In both Long COVID and ME/CFS, prolonged exposure to viral antigens results in hyperactivation of CD8 T cells. This leads to a chronic immune response that can cause extreme fatigue, sleep disturbances and cognitive problems.


𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬:
In mononucleosis, 𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐢𝐧 𝐭𝐡𝐞 𝐂𝐃𝟒 𝐓-𝐜𝐞𝐥𝐥 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞, caused by genetic factors such as certain HLA-II alleles, prevents the immune system from correctly recognizing viral antigens. This deficiency leads to an increase in the number of infected cells, resulting in increased activation of CD8 T cells in an attempt to eliminate the affected cells. This 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐂𝐃𝟖 𝐓-𝐜𝐞𝐥𝐥 𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 in response to CD4 T-cell insufficiency can result in 𝐨𝐯𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 of the immune system, leading to 𝐂𝐃𝟖 𝐓-𝐜𝐞𝐥𝐥 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 and increasing the risk of developing 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬, such as multiple sclerosis, due to the persistent presence of viral antigens.


𝐌𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐌𝐢𝐦𝐢𝐜𝐫𝐲:
This inefficiency in antigen recognition can lead to a phenomenon of molecular mimicry, where the immune system mistakes viral antigens for self antigens, exacerbating autoimmunity.


𝐀𝐧𝐝 𝐭𝐡𝐢𝐬 𝐢𝐬 𝐞𝐱𝐚𝐜𝐭𝐥𝐲 𝐰𝐡𝐚𝐭 𝐡𝐚𝐩𝐩𝐞𝐧𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: a persistent SARS-CoV-2 or EBV infection in patients with susceptible HLA-II alleles, whose CD4 T cells fail to control the infection. This leads to hyperactivation of CD8 T cells and their subsequent exhaustion, with the risk of developing autoimmune diseases due to the chronic presence of viral antigens. These antigens share similarities with self antigens, promoting autoimmunity, as these susceptible HLA-II alleles are also more promiscuous and enable this process.


Therefore, those patients who after EBV infection develop infectious mononucleosis are more likely to carry these ineffective HLA-II alleles, which could predispose them also to develop ME/CFS and EBV-associated autoimmune diseases, such as lupus or multiple sclerosis.


𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐇𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦: 𝐓𝐡𝐞 𝐑𝐨𝐥𝐞 𝐨𝐟 𝐇𝐋𝐀-𝐈𝐈 𝐒𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐀𝐥𝐥𝐞𝐥𝐞𝐬:

In 𝐌𝐄/𝐂𝐅𝐒 and 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, some patients develop 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬. This condition arises as a direct consequence of the inability of susceptible 𝐇𝐋𝐀-𝐈𝐈 alleles to effectively control viral infection, as mentioned above. This deficiency not only prolongs inflammation, but can also trigger an autoimmune response through 𝐦𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐦𝐢𝐦𝐢𝐜𝐫𝐲.

In this case, viral antigens mimic 𝐀𝐂𝐓𝐇 (adrenocorticotropic hormone) structures, a key hormone in the regulation of cortisol, leading to an autoimmune attack against the pituitary gland. This process results in 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 (low cortisol levels), aggravating fatigue, malaise and other symptoms.


𝐃𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐜𝐞𝐬 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐬𝐮𝐛𝐠𝐫𝐨𝐮𝐩𝐬: 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐚𝐧𝐝 𝐒𝐞𝐯𝐞𝐫𝐢𝐭𝐲 𝐨𝐟 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬:

• 𝐌𝐢𝐥𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬: although they do not develop pituitary autoimmunity, they experience CD8 T-cell hyperactivation and depletion, which also results in fatigue, sleep disturbances and cognitive problems. In addition, they exhibit 𝐞𝐥𝐞𝐯𝐚𝐭𝐞𝐝 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐥𝐞𝐯𝐞𝐥𝐬 in response to increased 𝐩𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞𝐬. These patients may recover without sequelae.
• 𝐌𝐨𝐝𝐞𝐫𝐚𝐭𝐞/𝐬𝐞𝐯𝐞𝐫𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬: develop 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 with hypocortisolism due to molecular mimicry between viral antigens and ACTH, leading to more severe symptoms. These patients may have autoimmune sequelae although the infection will be controlled. There is another possibility in some patients: an increase in 𝐠𝐥𝐮𝐜𝐨𝐜𝐨𝐫𝐭𝐢𝐜𝐨𝐢𝐝 𝐫𝐞𝐜𝐞𝐩𝐭𝐨𝐫 𝐫𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞, leading to an effect similar to hypocortisolism, as cortisol signaling is ineffective, aggravating symptoms of inflammation and fatigue.

In summary, both 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒, and 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 illustrate how a dysregulated immune response, facilitated by susceptible 𝐇𝐋𝐀-𝐈𝐈 alleles, can lead to persistent symptoms and autoimmunity. Autoimmune hypophysitis, caused by mimicry of viral antigens with 𝐀𝐂𝐓𝐇, is a key factor that may determine the severity of symptoms in many patients.

Moreover, the development of autoimmune diseases such as 𝐥𝐮𝐩𝐮𝐬 or 𝐦𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐬𝐜𝐥𝐞𝐫𝐨𝐬𝐢𝐬 has exactly the same developmental basis as these syndromes. In these diseases, the combination of a 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 together with 𝐬𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐇𝐋𝐀-𝐈𝐈 𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐬 results in the development of autoimmunity. Thus, all these diseases follow the same developmental model (I attach the outline of the model in the next post).

𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧 𝐨𝐟 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐟𝐨𝐫 𝐚𝐥𝐥 𝐭𝐡𝐞𝐬𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬:
The key is to address both the 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 through the use of specific antivirals, and to treat the 𝐩𝐞𝐫𝐦𝐚𝐧𝐞𝐧𝐭 𝐝𝐚𝐦𝐚𝐠𝐞 caused by autoimmunity.


𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬. Time to better diagnose these conditions diseases and their consequences!


#LongCOVID #MECFS #health.

Image of the developmental model of autoimmune hypophysitis. This model can be extrapolated to the development of other autoimmune diseases and CD8 T-cell hyperactivation:

- Substitute myelin or any autoimmune disease-associated antigen for ACTH in the scheme.
- Substitute HLA-DR15 for the allele that is susceptible to a deficient response against the antigen.

 

[Angel Bryan]

𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐧𝐠 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐌𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬: 𝐓𝐡𝐞 𝐑𝐨𝐥𝐞 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐂𝐞𝐥𝐥𝐬 𝐢𝐧 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬

Did you know that syndromes such as 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒 and 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 share a common immune mechanism?


𝐂𝐨𝐧𝐭𝐢𝐧𝐮𝐨𝐮𝐬 𝐂𝐃𝟖 𝐓 𝐂𝐞𝐥𝐥 𝐀𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧:
In both Long COVID and ME/CFS, prolonged exposure to viral antigens results in hyperactivation of CD8 T cells. This leads to a chronic immune response that can cause extreme fatigue, sleep disturbances and cognitive problems.


𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬:
In mononucleosis, 𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐢𝐧 𝐭𝐡𝐞 𝐂𝐃𝟒 𝐓-𝐜𝐞𝐥𝐥 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞, caused by genetic factors such as certain HLA-II alleles, prevents the immune system from correctly recognizing viral antigens. This deficiency leads to an increase in the number of infected cells, resulting in increased activation of CD8 T cells in an attempt to eliminate the affected cells. This 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐂𝐃𝟖 𝐓-𝐜𝐞𝐥𝐥 𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 in response to CD4 T-cell insufficiency can result in 𝐨𝐯𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 of the immune system, leading to 𝐂𝐃𝟖 𝐓-𝐜𝐞𝐥𝐥 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 and increasing the risk of developing 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬, such as multiple sclerosis, due to the persistent presence of viral antigens.


𝐌𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐌𝐢𝐦𝐢𝐜𝐫𝐲:
This inefficiency in antigen recognition can lead to a phenomenon of molecular mimicry, where the immune system mistakes viral antigens for self antigens, exacerbating autoimmunity.


𝐀𝐧𝐝 𝐭𝐡𝐢𝐬 𝐢𝐬 𝐞𝐱𝐚𝐜𝐭𝐥𝐲 𝐰𝐡𝐚𝐭 𝐡𝐚𝐩𝐩𝐞𝐧𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: a persistent SARS-CoV-2 or EBV infection in patients with susceptible HLA-II alleles, whose CD4 T cells fail to control the infection. This leads to hyperactivation of CD8 T cells and their subsequent exhaustion, with the risk of developing autoimmune diseases due to the chronic presence of viral antigens. These antigens share similarities with self antigens, promoting autoimmunity, as these susceptible HLA-II alleles are also more promiscuous and enable this process.


Therefore, those patients who after EBV infection develop infectious mononucleosis are more likely to carry these ineffective HLA-II alleles, which could predispose them also to develop ME/CFS and EBV-associated autoimmune diseases, such as lupus or multiple sclerosis.


𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐇𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦: 𝐓𝐡𝐞 𝐑𝐨𝐥𝐞 𝐨𝐟 𝐇𝐋𝐀-𝐈𝐈 𝐒𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐀𝐥𝐥𝐞𝐥𝐞𝐬:

In 𝐌𝐄/𝐂𝐅𝐒 and 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, some patients develop 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬. This condition arises as a direct consequence of the inability of susceptible 𝐇𝐋𝐀-𝐈𝐈 alleles to effectively control viral infection, as mentioned above. This deficiency not only prolongs inflammation, but can also trigger an autoimmune response through 𝐦𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐦𝐢𝐦𝐢𝐜𝐫𝐲.

In this case, viral antigens mimic 𝐀𝐂𝐓𝐇 (adrenocorticotropic hormone) structures, a key hormone in the regulation of cortisol, leading to an autoimmune attack against the pituitary gland. This process results in 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 (low cortisol levels), aggravating fatigue, malaise and other symptoms.


𝐃𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐜𝐞𝐬 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐬𝐮𝐛𝐠𝐫𝐨𝐮𝐩𝐬: 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐚𝐧𝐝 𝐒𝐞𝐯𝐞𝐫𝐢𝐭𝐲 𝐨𝐟 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬:

• 𝐌𝐢𝐥𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬: although they do not develop pituitary autoimmunity, they experience CD8 T-cell hyperactivation and depletion, which also results in fatigue, sleep disturbances and cognitive problems. In addition, they exhibit 𝐞𝐥𝐞𝐯𝐚𝐭𝐞𝐝 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐥𝐞𝐯𝐞𝐥𝐬 in response to increased 𝐩𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞𝐬. These patients may recover without sequelae.
• 𝐌𝐨𝐝𝐞𝐫𝐚𝐭𝐞/𝐬𝐞𝐯𝐞𝐫𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬: develop 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 with hypocortisolism due to molecular mimicry between viral antigens and ACTH, leading to more severe symptoms. These patients may have autoimmune sequelae although the infection will be controlled. There is another possibility in some patients: an increase in 𝐠𝐥𝐮𝐜𝐨𝐜𝐨𝐫𝐭𝐢𝐜𝐨𝐢𝐝 𝐫𝐞𝐜𝐞𝐩𝐭𝐨𝐫 𝐫𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞, leading to an effect similar to hypocortisolism, as cortisol signaling is ineffective, aggravating symptoms of inflammation and fatigue.

In summary, both 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐄/𝐂𝐅𝐒, and 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 illustrate how a dysregulated immune response, facilitated by susceptible 𝐇𝐋𝐀-𝐈𝐈 alleles, can lead to persistent symptoms and autoimmunity. Autoimmune hypophysitis, caused by mimicry of viral antigens with 𝐀𝐂𝐓𝐇, is a key factor that may determine the severity of symptoms in many patients.

Moreover, the development of autoimmune diseases such as 𝐥𝐮𝐩𝐮𝐬 or 𝐦𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐬𝐜𝐥𝐞𝐫𝐨𝐬𝐢𝐬 has exactly the same developmental basis as these syndromes. In these diseases, the combination of a 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 together with 𝐬𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐇𝐋𝐀-𝐈𝐈 𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐬 results in the development of autoimmunity. Thus, all these diseases follow the same developmental model (I attach the outline of the model in the next post).

𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧 𝐨𝐟 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐟𝐨𝐫 𝐚𝐥𝐥 𝐭𝐡𝐞𝐬𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬:
The key is to address both the 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 through the use of specific antivirals, and to treat the 𝐩𝐞𝐫𝐦𝐚𝐧𝐞𝐧𝐭 𝐝𝐚𝐦𝐚𝐠𝐞 caused by autoimmunity.


𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬. Time to better diagnose these conditions diseases and their consequences!


#LongCOVID #MECFS #health.

Image of the developmental model of autoimmune hypophysitis. This model can be extrapolated to the development of other autoimmune diseases and CD8 T-cell hyperactivation:

- Substitute myelin or any autoimmune disease-associated antigen for ACTH in the scheme.
- Substitute HLA-DR15 for the allele that is susceptible to a deficient response against the antigen.

I am mild and have been sick for 10 months already. Does it means I have the chance of recoveryng naturally? How can I reduce CD8 T-cell hyperactivity?

 

[Aidan Walsh]

Hi Manuel,, are you able to check for levels in your lab to see if D-LACTATE ACIDOSIS comes up. Avenger has posted on this on here in the past. I did the blood test recently it came back High Positive.

The normal result ranges in the UK are 120-246UL mine was 480UL

Thank you for your continued research we appreciate all your Teams important work for answers

 

[Manuel]

𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: 𝐓𝐡𝐞 𝐔𝐧𝐞𝐱𝐩𝐞𝐜𝐭𝐞𝐝 𝐅𝐥𝐢𝐩 𝐒𝐢𝐝𝐞 𝐨𝐟 𝐃𝐢𝐚𝐛𝐞𝐭𝐞𝐬 𝐘𝐨𝐮 𝐒𝐡𝐨𝐮𝐥𝐝 𝐊𝐧𝐨𝐰 𝐀𝐛𝐨𝐮𝐭.

Stay to the end to understand the relationship of these diseases to the opposite case of diabetes!

𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐌𝐄/𝐂𝐅𝐒) are affecting millions of people worldwide. But why do these conditions cause such overwhelming fatigue? The answer may lie in a fascinating theory: both disorders may be linked to 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬, in which the immune system attacks the pituitary gland, affecting 𝐀𝐂𝐓𝐇 production and resulting in 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 (low cortisol levels).

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐚𝐧𝐝 𝐰𝐡𝐲 𝐢𝐬 𝐢𝐭 𝐜𝐫𝐮𝐜𝐢𝐚𝐥?
Cortisol is an essential hormone for 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐧𝐠 𝐛𝐥𝐨𝐨𝐝 𝐠𝐥𝐮𝐜𝐨𝐬𝐞, especially in situations of 𝐛𝐢𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐬𝐭𝐫𝐞𝐬𝐬 or 𝐩𝐫𝐨𝐥𝐨𝐧𝐠𝐞𝐝 𝐟𝐚𝐬𝐭𝐢𝐧𝐠. When cortisol levels are low, as occurs in hypocortisolism, the body has difficulty increasing glucose through 𝐬𝐮𝐬𝐭𝐚𝐢𝐧𝐞𝐝 𝐠𝐥𝐮𝐜𝐨𝐧𝐞𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬, affecting the ability to maintain constant energy levels. This causes 𝐬𝐩𝐢𝐤𝐞𝐬 𝐢𝐧 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚 and explains the intense fatigue and mental confusion that many patients experience. Without sufficient energy, the brain and muscles cannot function properly.


𝐓𝐡𝐞 𝐁𝐨𝐝𝐲'𝐬 𝐑𝐞𝐬𝐩𝐨𝐧𝐬𝐞 𝐭𝐨 𝐇𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚
When the body detects 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚, the 𝐡𝐲𝐩𝐨𝐭𝐡𝐚𝐥𝐚𝐦𝐮𝐬 sends signals to the sympathetic nervous system, which in turn stimulates the medulla of the adrenal glands to release 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞. This hormone rapidly increases glucose levels by activating 𝐠𝐥𝐲𝐜𝐨𝐠𝐞𝐧𝐨𝐥𝐲𝐬𝐢𝐬 (release of glucose from the liver) and reducing insulin activity. However, this emergency mechanism is not always sufficient without the long-term support of cortisol, which is essential for maintaining sustained elevated glucose in situations of stress or prolonged fasting.

In addition to adrenaline, 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧 and 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) also counteract hypoglycemia:

𝐆𝐥𝐮𝐜𝐚𝐠𝐨𝐧: Acts rapidly in response to mild to moderate hypoglycemia by stimulating the release of glucose in the liver. Its action is essential for the rapid adjustment of blood glucose.
𝐆𝐇: Although its role is minor compared to glucagon and cortisol, it contributes to raising glucose by reducing its uptake in tissues and stimulating its production in the liver.

These hormones help to partially compensate for the lack of cortisol in the short term. However, because of their compensatory action, 𝐝𝐞𝐭𝐞𝐜𝐭𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚𝐬 𝐫𝐞𝐥𝐚𝐭𝐞𝐝 𝐭𝐨 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐬𝐩𝐨𝐭 𝐭𝐞𝐬𝐭𝐬 𝐜𝐚𝐧 𝐛𝐞 𝐜𝐨𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐞𝐝.

𝐀 𝐯𝐢𝐜𝐢𝐨𝐮𝐬 𝐜𝐲𝐜𝐥𝐞 𝐨𝐟 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬.
When hypocortisolism is persistent, the body fails to maintain an adequate long-term glucose supply, leading to a state of chronic energy crisis. This constant deficit causes fatigue, dizziness and symptoms associated with Long COVID and ME/CFS.

Hypocortisolism also perpetuates immune depletion. Without sufficient cortisol, the immune system is not properly regulated, becomes overactive and promotes autoimmunity and a chronic increase in IFN-gamma, a pro-inflammatory cytokine. Not only does this generate a destructive cycle of inflammation and damage, but cortisol deficiency also compromises the immune system's ability to fight infection, making the body more vulnerable to external pathogens and viral reactivations.

𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐬𝐨𝐧 𝐰𝐢𝐭𝐡 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬.
This phenomenon is curious, as it bears similarities to 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬 but in the opposite way. In type 1 diabetes, lack of insulin causes hyperglycemia (high blood glucose levels). In Long COVID and ME/CFS, the lack of cortisol prevents the body from raising glucose when needed, resulting in hypoglycemia. The presence of glucagon and GH acts as a defense, but cannot be sustained over time without cortisol support.

Imagine studying type 1 diabetes without knowing that insulin is missing; it would be difficult to understand all the symptoms. The same is true for Long COVID and ME/CFS: many studies focus on the consequences and symptoms without considering that a 𝐡𝐨𝐫𝐦𝐨𝐧𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 could be at the root of many of the problems.

𝐓𝐡𝐞 𝐢𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐜𝐞 𝐨𝐟 𝐩𝐫𝐨𝐩𝐞𝐫 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐢𝐬.
Without cortisol, the body cannot mobilize glucose in a sustained manner, explaining not only chronic fatigue, but also difficulty managing stress and engaging in physical activity. In many patients with hypocortisolism, such as those with adrenal insufficiency, hypoglycemias are difficult to detect in spot tests due to the compensatory action of glucagon and GH. For proper detection of hypoglycemias in patients with Long COVID and ME/CFS, it would be ideal to perform glucose checks at strategic times, especially at night and during periods of stress or fasting.

In 𝐦𝐢𝐥𝐝𝐞𝐫 cases of Long COVID and ME/CFS, patients may not have autoimmunity, but rather only 𝐢𝐦𝐦𝐮𝐧𝐞 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 due to 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 and 𝐡𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐜𝐞𝐥𝐥𝐬, similar to what occurs in 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬

If this hypothesis is correct, research on Long COVID and ME/CFS may be revealing an underlying hormonal dysfunction. Rather than treating only the symptoms, it would be crucial to address the root of the problem: persistent infection and autoimmune dysfunction affecting the hypothalamic-pituitary-adrenal axis. This may require antiviral and hormonal treatment to improve the patients' quality of life.

𝐈𝐧 𝐭𝐡𝐞 𝐧𝐞𝐱𝐭 𝐩𝐨𝐬𝐭 𝐨𝐟 𝐭𝐡𝐢𝐬 𝐭𝐡𝐫𝐞𝐚𝐝 I attach two diagrams illustrating the difficulty of regulating glucose levels in patients with hypocortisolemia in ME/CFS and Long COVID.

𝐒𝐡𝐚𝐫𝐞 this information with physicians and patients - it's time to better understand these conditions and their repercussions!

#LongCOVID #MECFS #health.


𝐒𝐜𝐡𝐞𝐦𝐞𝐬 𝐨𝐟 𝐁𝐥𝐨𝐨𝐝 𝐆𝐥𝐮𝐜𝐨𝐬𝐞 𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐃𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐒𝐭𝐚𝐭𝐞𝐬: 𝐁𝐚𝐬𝐚𝐥 𝐯𝐬. 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬
These schemes illustrate how the body regulates blood glucose levels (blood glucose) in two scenarios: the basal (resting) state and during physical stress or exercise.

𝐁𝐚𝐬𝐚𝐥 (𝐑𝐞𝐬𝐭𝐢𝐧𝐠) 𝐒𝐭𝐚𝐭𝐞
At rest, the body maintains stable glucose mainly through the action of 𝐢𝐧𝐬𝐮𝐥𝐢𝐧 and 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧, which act in the short term. Alpha cells of the pancreas produce glucagon, which raises glucose when it is low, while beta cells release insulin to lower it when it is high, regulating post-meal glucose.

Other hormones, such as 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) and, to a lesser extent, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥, contribute in the long term to the maintenance of energy metabolism. Adrenaline has a minimal role in the basal state, but can be activated in the face of acute hypoglycemia.

𝐈𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐭: In people with hypocortisolism, this basal regulation is altered, making it difficult for the body to maintain stable glucose levels, especially in situations of prolonged fasting or physical exercise.

𝐒𝐭𝐚𝐭𝐞 𝐨𝐟 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬 𝐨𝐫 𝐄𝐱𝐞𝐫𝐜𝐢𝐬𝐞
In stressful situations, such as exercise, the body needs additional energy and therefore requires fast and sustained response hormones. Here, 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞 plays a crucial role in the 𝐬𝐡𝐨𝐫𝐭 𝐭𝐞𝐫𝐦, mobilizing glucose from the liver to provide rapid energy.

In addition, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 comes into play in the 𝐥𝐨𝐧𝐠 𝐭𝐞𝐫𝐦, promoting a sustained release of glucose to maintain energy during prolonged exercise. 𝐆𝐇 also supports this process, although its effect is secondary and less direct than that of adrenaline and cortisol. Together, these hormones ensure that the body has enough glucose to respond to physical stress effectively.

𝐍𝐨𝐭𝐞: In conditions such as Long COVID or ME/CFS, possible autoimmunity or inflammation can affect the pituitary gland, decreasing cortisol production and hindering glucose regulation during physical stress, contributing to cycles of hypoglycemia and fatigue.

These schemes show how glucose regulation adapts to the body's energy demands, and how a lack of cortisol in certain patients can lead to constant fatigue and difficulties responding to physical stress.

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐗 𝐭𝐡𝐫𝐞𝐚𝐝: https://x.com/manruipa/status/1850159699263361300

 

[Aidan Walsh]

View attachment 54712 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: 𝐓𝐡𝐞 𝐔𝐧𝐞𝐱𝐩𝐞𝐜𝐭𝐞𝐝 𝐅𝐥𝐢𝐩 𝐒𝐢𝐝𝐞 𝐨𝐟 𝐃𝐢𝐚𝐛𝐞𝐭𝐞𝐬 𝐘𝐨𝐮 𝐒𝐡𝐨𝐮𝐥𝐝 𝐊𝐧𝐨𝐰 𝐀𝐛𝐨𝐮𝐭.

Stay to the end to understand the relationship of these diseases to the opposite case of diabetes!

𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐌𝐄/𝐂𝐅𝐒) are affecting millions of people worldwide. But why do these conditions cause such overwhelming fatigue? The answer may lie in a fascinating theory: both disorders may be linked to 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬, in which the immune system attacks the pituitary gland, affecting 𝐀𝐂𝐓𝐇 production and resulting in 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 (low cortisol levels).

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐚𝐧𝐝 𝐰𝐡𝐲 𝐢𝐬 𝐢𝐭 𝐜𝐫𝐮𝐜𝐢𝐚𝐥?
Cortisol is an essential hormone for 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐧𝐠 𝐛𝐥𝐨𝐨𝐝 𝐠𝐥𝐮𝐜𝐨𝐬𝐞, especially in situations of 𝐛𝐢𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐬𝐭𝐫𝐞𝐬𝐬 or 𝐩𝐫𝐨𝐥𝐨𝐧𝐠𝐞𝐝 𝐟𝐚𝐬𝐭𝐢𝐧𝐠. When cortisol levels are low, as occurs in hypocortisolism, the body has difficulty increasing glucose through 𝐬𝐮𝐬𝐭𝐚𝐢𝐧𝐞𝐝 𝐠𝐥𝐮𝐜𝐨𝐧𝐞𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬, affecting the ability to maintain constant energy levels. This causes 𝐬𝐩𝐢𝐤𝐞𝐬 𝐢𝐧 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚 and explains the intense fatigue and mental confusion that many patients experience. Without sufficient energy, the brain and muscles cannot function properly.


𝐓𝐡𝐞 𝐁𝐨𝐝𝐲'𝐬 𝐑𝐞𝐬𝐩𝐨𝐧𝐬𝐞 𝐭𝐨 𝐇𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚
When the body detects 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚, the 𝐡𝐲𝐩𝐨𝐭𝐡𝐚𝐥𝐚𝐦𝐮𝐬 sends signals to the sympathetic nervous system, which in turn stimulates the medulla of the adrenal glands to release 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞. This hormone rapidly increases glucose levels by activating 𝐠𝐥𝐲𝐜𝐨𝐠𝐞𝐧𝐨𝐥𝐲𝐬𝐢𝐬 (release of glucose from the liver) and reducing insulin activity. However, this emergency mechanism is not always sufficient without the long-term support of cortisol, which is essential for maintaining sustained elevated glucose in situations of stress or prolonged fasting.

In addition to adrenaline, 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧 and 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) also counteract hypoglycemia:

𝐆𝐥𝐮𝐜𝐚𝐠𝐨𝐧: Acts rapidly in response to mild to moderate hypoglycemia by stimulating the release of glucose in the liver. Its action is essential for the rapid adjustment of blood glucose.
𝐆𝐇: Although its role is minor compared to glucagon and cortisol, it contributes to raising glucose by reducing its uptake in tissues and stimulating its production in the liver.

These hormones help to partially compensate for the lack of cortisol in the short term. However, because of their compensatory action, 𝐝𝐞𝐭𝐞𝐜𝐭𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚𝐬 𝐫𝐞𝐥𝐚𝐭𝐞𝐝 𝐭𝐨 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐬𝐩𝐨𝐭 𝐭𝐞𝐬𝐭𝐬 𝐜𝐚𝐧 𝐛𝐞 𝐜𝐨𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐞𝐝.

𝐀 𝐯𝐢𝐜𝐢𝐨𝐮𝐬 𝐜𝐲𝐜𝐥𝐞 𝐨𝐟 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬.
When hypocortisolism is persistent, the body fails to maintain an adequate long-term glucose supply, leading to a state of chronic energy crisis. This constant deficit causes fatigue, dizziness and symptoms associated with Long COVID and ME/CFS.

Hypocortisolism also perpetuates immune depletion. Without sufficient cortisol, the immune system is not properly regulated, becomes overactive and promotes autoimmunity and a chronic increase in IFN-gamma, a pro-inflammatory cytokine. Not only does this generate a destructive cycle of inflammation and damage, but cortisol deficiency also compromises the immune system's ability to fight infection, making the body more vulnerable to external pathogens and viral reactivations.

𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐬𝐨𝐧 𝐰𝐢𝐭𝐡 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬.
This phenomenon is curious, as it bears similarities to 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬 but in the opposite way. In type 1 diabetes, lack of insulin causes hyperglycemia (high blood glucose levels). In Long COVID and ME/CFS, the lack of cortisol prevents the body from raising glucose when needed, resulting in hypoglycemia. The presence of glucagon and GH acts as a defense, but cannot be sustained over time without cortisol support.

Imagine studying type 1 diabetes without knowing that insulin is missing; it would be difficult to understand all the symptoms. The same is true for Long COVID and ME/CFS: many studies focus on the consequences and symptoms without considering that a 𝐡𝐨𝐫𝐦𝐨𝐧𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 could be at the root of many of the problems.

𝐓𝐡𝐞 𝐢𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐜𝐞 𝐨𝐟 𝐩𝐫𝐨𝐩𝐞𝐫 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐢𝐬.
Without cortisol, the body cannot mobilize glucose in a sustained manner, explaining not only chronic fatigue, but also difficulty managing stress and engaging in physical activity. In many patients with hypocortisolism, such as those with adrenal insufficiency, hypoglycemias are difficult to detect in spot tests due to the compensatory action of glucagon and GH. For proper detection of hypoglycemias in patients with Long COVID and ME/CFS, it would be ideal to perform glucose checks at strategic times, especially at night and during periods of stress or fasting.

In 𝐦𝐢𝐥𝐝𝐞𝐫 cases of Long COVID and ME/CFS, patients may not have autoimmunity, but rather only 𝐢𝐦𝐦𝐮𝐧𝐞 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 due to 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 and 𝐡𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐜𝐞𝐥𝐥𝐬, similar to what occurs in 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬

If this hypothesis is correct, research on Long COVID and ME/CFS may be revealing an underlying hormonal dysfunction. Rather than treating only the symptoms, it would be crucial to address the root of the problem: persistent infection and autoimmune dysfunction affecting the hypothalamic-pituitary-adrenal axis. This may require antiviral and hormonal treatment to improve the patients' quality of life.

𝐈𝐧 𝐭𝐡𝐞 𝐧𝐞𝐱𝐭 𝐩𝐨𝐬𝐭 𝐨𝐟 𝐭𝐡𝐢𝐬 𝐭𝐡𝐫𝐞𝐚𝐝 I attach two diagrams illustrating the difficulty of regulating glucose levels in patients with hypocortisolemia in ME/CFS and Long COVID.

𝐒𝐡𝐚𝐫𝐞 this information with physicians and patients - it's time to better understand these conditions and their repercussions!

#LongCOVID #MECFS #health.


𝐒𝐜𝐡𝐞𝐦𝐞𝐬 𝐨𝐟 𝐁𝐥𝐨𝐨𝐝 𝐆𝐥𝐮𝐜𝐨𝐬𝐞 𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐃𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐒𝐭𝐚𝐭𝐞𝐬: 𝐁𝐚𝐬𝐚𝐥 𝐯𝐬. 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬
These schemes illustrate how the body regulates blood glucose levels (blood glucose) in two scenarios: the basal (resting) state and during physical stress or exercise.

𝐁𝐚𝐬𝐚𝐥 (𝐑𝐞𝐬𝐭𝐢𝐧𝐠) 𝐒𝐭𝐚𝐭𝐞
At rest, the body maintains stable glucose mainly through the action of 𝐢𝐧𝐬𝐮𝐥𝐢𝐧 and 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧, which act in the short term. Alpha cells of the pancreas produce glucagon, which raises glucose when it is low, while beta cells release insulin to lower it when it is high, regulating post-meal glucose.

Other hormones, such as 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) and, to a lesser extent, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥, contribute in the long term to the maintenance of energy metabolism. Adrenaline has a minimal role in the basal state, but can be activated in the face of acute hypoglycemia.

𝐈𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐭: In people with hypocortisolism, this basal regulation is altered, making it difficult for the body to maintain stable glucose levels, especially in situations of prolonged fasting or physical exercise.

View attachment 54713

𝐒𝐭𝐚𝐭𝐞 𝐨𝐟 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬 𝐨𝐫 𝐄𝐱𝐞𝐫𝐜𝐢𝐬𝐞
In stressful situations, such as exercise, the body needs additional energy and therefore requires fast and sustained response hormones. Here, 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞 plays a crucial role in the 𝐬𝐡𝐨𝐫𝐭 𝐭𝐞𝐫𝐦, mobilizing glucose from the liver to provide rapid energy.

In addition, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 comes into play in the 𝐥𝐨𝐧𝐠 𝐭𝐞𝐫𝐦, promoting a sustained release of glucose to maintain energy during prolonged exercise. 𝐆𝐇 also supports this process, although its effect is secondary and less direct than that of adrenaline and cortisol. Together, these hormones ensure that the body has enough glucose to respond to physical stress effectively.

𝐍𝐨𝐭𝐞: In conditions such as Long COVID or ME/CFS, possible autoimmunity or inflammation can affect the pituitary gland, decreasing cortisol production and hindering glucose regulation during physical stress, contributing to cycles of hypoglycemia and fatigue.
View attachment 54714

These schemes show how glucose regulation adapts to the body's energy demands, and how a lack of cortisol in certain patients can lead to constant fatigue and difficulties responding to physical stress.

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐗 𝐭𝐡𝐫𝐞𝐚𝐝: https://x.com/manruipa/status/1850159699263361300

View attachment 54712 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: 𝐓𝐡𝐞 𝐔𝐧𝐞𝐱𝐩𝐞𝐜𝐭𝐞𝐝 𝐅𝐥𝐢𝐩 𝐒𝐢𝐝𝐞 𝐨𝐟 𝐃𝐢𝐚𝐛𝐞𝐭𝐞𝐬 𝐘𝐨𝐮 𝐒𝐡𝐨𝐮𝐥𝐝 𝐊𝐧𝐨𝐰 𝐀𝐛𝐨𝐮𝐭.

Stay to the end to understand the relationship of these diseases to the opposite case of diabetes!

𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐌𝐄/𝐂𝐅𝐒) are affecting millions of people worldwide. But why do these conditions cause such overwhelming fatigue? The answer may lie in a fascinating theory: both disorders may be linked to 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬, in which the immune system attacks the pituitary gland, affecting 𝐀𝐂𝐓𝐇 production and resulting in 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 (low cortisol levels).

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐚𝐧𝐝 𝐰𝐡𝐲 𝐢𝐬 𝐢𝐭 𝐜𝐫𝐮𝐜𝐢𝐚𝐥?
Cortisol is an essential hormone for 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐧𝐠 𝐛𝐥𝐨𝐨𝐝 𝐠𝐥𝐮𝐜𝐨𝐬𝐞, especially in situations of 𝐛𝐢𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐬𝐭𝐫𝐞𝐬𝐬 or 𝐩𝐫𝐨𝐥𝐨𝐧𝐠𝐞𝐝 𝐟𝐚𝐬𝐭𝐢𝐧𝐠. When cortisol levels are low, as occurs in hypocortisolism, the body has difficulty increasing glucose through 𝐬𝐮𝐬𝐭𝐚𝐢𝐧𝐞𝐝 𝐠𝐥𝐮𝐜𝐨𝐧𝐞𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬, affecting the ability to maintain constant energy levels. This causes 𝐬𝐩𝐢𝐤𝐞𝐬 𝐢𝐧 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚 and explains the intense fatigue and mental confusion that many patients experience. Without sufficient energy, the brain and muscles cannot function properly.


𝐓𝐡𝐞 𝐁𝐨𝐝𝐲'𝐬 𝐑𝐞𝐬𝐩𝐨𝐧𝐬𝐞 𝐭𝐨 𝐇𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚
When the body detects 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚, the 𝐡𝐲𝐩𝐨𝐭𝐡𝐚𝐥𝐚𝐦𝐮𝐬 sends signals to the sympathetic nervous system, which in turn stimulates the medulla of the adrenal glands to release 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞. This hormone rapidly increases glucose levels by activating 𝐠𝐥𝐲𝐜𝐨𝐠𝐞𝐧𝐨𝐥𝐲𝐬𝐢𝐬 (release of glucose from the liver) and reducing insulin activity. However, this emergency mechanism is not always sufficient without the long-term support of cortisol, which is essential for maintaining sustained elevated glucose in situations of stress or prolonged fasting.

In addition to adrenaline, 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧 and 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) also counteract hypoglycemia:

𝐆𝐥𝐮𝐜𝐚𝐠𝐨𝐧: Acts rapidly in response to mild to moderate hypoglycemia by stimulating the release of glucose in the liver. Its action is essential for the rapid adjustment of blood glucose.
𝐆𝐇: Although its role is minor compared to glucagon and cortisol, it contributes to raising glucose by reducing its uptake in tissues and stimulating its production in the liver.

These hormones help to partially compensate for the lack of cortisol in the short term. However, because of their compensatory action, 𝐝𝐞𝐭𝐞𝐜𝐭𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚𝐬 𝐫𝐞𝐥𝐚𝐭𝐞𝐝 𝐭𝐨 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐬𝐩𝐨𝐭 𝐭𝐞𝐬𝐭𝐬 𝐜𝐚𝐧 𝐛𝐞 𝐜𝐨𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐞𝐝.

𝐀 𝐯𝐢𝐜𝐢𝐨𝐮𝐬 𝐜𝐲𝐜𝐥𝐞 𝐨𝐟 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬.
When hypocortisolism is persistent, the body fails to maintain an adequate long-term glucose supply, leading to a state of chronic energy crisis. This constant deficit causes fatigue, dizziness and symptoms associated with Long COVID and ME/CFS.

Hypocortisolism also perpetuates immune depletion. Without sufficient cortisol, the immune system is not properly regulated, becomes overactive and promotes autoimmunity and a chronic increase in IFN-gamma, a pro-inflammatory cytokine. Not only does this generate a destructive cycle of inflammation and damage, but cortisol deficiency also compromises the immune system's ability to fight infection, making the body more vulnerable to external pathogens and viral reactivations.

𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐬𝐨𝐧 𝐰𝐢𝐭𝐡 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬.
This phenomenon is curious, as it bears similarities to 𝐭𝐲𝐩𝐞 𝟏 𝐝𝐢𝐚𝐛𝐞𝐭𝐞𝐬 but in the opposite way. In type 1 diabetes, lack of insulin causes hyperglycemia (high blood glucose levels). In Long COVID and ME/CFS, the lack of cortisol prevents the body from raising glucose when needed, resulting in hypoglycemia. The presence of glucagon and GH acts as a defense, but cannot be sustained over time without cortisol support.

Imagine studying type 1 diabetes without knowing that insulin is missing; it would be difficult to understand all the symptoms. The same is true for Long COVID and ME/CFS: many studies focus on the consequences and symptoms without considering that a 𝐡𝐨𝐫𝐦𝐨𝐧𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 could be at the root of many of the problems.

𝐓𝐡𝐞 𝐢𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐜𝐞 𝐨𝐟 𝐩𝐫𝐨𝐩𝐞𝐫 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐢𝐬.
Without cortisol, the body cannot mobilize glucose in a sustained manner, explaining not only chronic fatigue, but also difficulty managing stress and engaging in physical activity. In many patients with hypocortisolism, such as those with adrenal insufficiency, hypoglycemias are difficult to detect in spot tests due to the compensatory action of glucagon and GH. For proper detection of hypoglycemias in patients with Long COVID and ME/CFS, it would be ideal to perform glucose checks at strategic times, especially at night and during periods of stress or fasting.

In 𝐦𝐢𝐥𝐝𝐞𝐫 cases of Long COVID and ME/CFS, patients may not have autoimmunity, but rather only 𝐢𝐦𝐦𝐮𝐧𝐞 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 due to 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 and 𝐡𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐜𝐞𝐥𝐥𝐬, similar to what occurs in 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐦𝐨𝐧𝐨𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐢𝐬 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬

If this hypothesis is correct, research on Long COVID and ME/CFS may be revealing an underlying hormonal dysfunction. Rather than treating only the symptoms, it would be crucial to address the root of the problem: persistent infection and autoimmune dysfunction affecting the hypothalamic-pituitary-adrenal axis. This may require antiviral and hormonal treatment to improve the patients' quality of life.

𝐈𝐧 𝐭𝐡𝐞 𝐧𝐞𝐱𝐭 𝐩𝐨𝐬𝐭 𝐨𝐟 𝐭𝐡𝐢𝐬 𝐭𝐡𝐫𝐞𝐚𝐝 I attach two diagrams illustrating the difficulty of regulating glucose levels in patients with hypocortisolemia in ME/CFS and Long COVID.

𝐒𝐡𝐚𝐫𝐞 this information with physicians and patients - it's time to better understand these conditions and their repercussions!

#LongCOVID #MECFS #health.


𝐒𝐜𝐡𝐞𝐦𝐞𝐬 𝐨𝐟 𝐁𝐥𝐨𝐨𝐝 𝐆𝐥𝐮𝐜𝐨𝐬𝐞 𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐃𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐒𝐭𝐚𝐭𝐞𝐬: 𝐁𝐚𝐬𝐚𝐥 𝐯𝐬. 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬
These schemes illustrate how the body regulates blood glucose levels (blood glucose) in two scenarios: the basal (resting) state and during physical stress or exercise.

𝐁𝐚𝐬𝐚𝐥 (𝐑𝐞𝐬𝐭𝐢𝐧𝐠) 𝐒𝐭𝐚𝐭𝐞
At rest, the body maintains stable glucose mainly through the action of 𝐢𝐧𝐬𝐮𝐥𝐢𝐧 and 𝐠𝐥𝐮𝐜𝐚𝐠𝐨𝐧, which act in the short term. Alpha cells of the pancreas produce glucagon, which raises glucose when it is low, while beta cells release insulin to lower it when it is high, regulating post-meal glucose.

Other hormones, such as 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞 (𝐆𝐇) and, to a lesser extent, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥, contribute in the long term to the maintenance of energy metabolism. Adrenaline has a minimal role in the basal state, but can be activated in the face of acute hypoglycemia.

𝐈𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐭: In people with hypocortisolism, this basal regulation is altered, making it difficult for the body to maintain stable glucose levels, especially in situations of prolonged fasting or physical exercise.

View attachment 54713

𝐒𝐭𝐚𝐭𝐞 𝐨𝐟 𝐏𝐡𝐲𝐬𝐢𝐜𝐚𝐥 𝐒𝐭𝐫𝐞𝐬𝐬 𝐨𝐫 𝐄𝐱𝐞𝐫𝐜𝐢𝐬𝐞
In stressful situations, such as exercise, the body needs additional energy and therefore requires fast and sustained response hormones. Here, 𝐚𝐝𝐫𝐞𝐧𝐚𝐥𝐢𝐧𝐞 plays a crucial role in the 𝐬𝐡𝐨𝐫𝐭 𝐭𝐞𝐫𝐦, mobilizing glucose from the liver to provide rapid energy.

In addition, 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 comes into play in the 𝐥𝐨𝐧𝐠 𝐭𝐞𝐫𝐦, promoting a sustained release of glucose to maintain energy during prolonged exercise. 𝐆𝐇 also supports this process, although its effect is secondary and less direct than that of adrenaline and cortisol. Together, these hormones ensure that the body has enough glucose to respond to physical stress effectively.

𝐍𝐨𝐭𝐞: In conditions such as Long COVID or ME/CFS, possible autoimmunity or inflammation can affect the pituitary gland, decreasing cortisol production and hindering glucose regulation during physical stress, contributing to cycles of hypoglycemia and fatigue.
View attachment 54714

These schemes show how glucose regulation adapts to the body's energy demands, and how a lack of cortisol in certain patients can lead to constant fatigue and difficulties responding to physical stress.

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐗 𝐭𝐡𝐫𝐞𝐚𝐝: https://x.com/manruipa/status/1850159699263361300

How does this above explain my high levels of D-LACTATE ACIDOSIS AT 480UL?

 

[Manuel]

𝐖𝐡𝐚𝐭 𝐦𝐨𝐫𝐞 𝐢𝐬 𝐧𝐞𝐞𝐝𝐞𝐝 𝐭𝐨 𝐭𝐚𝐤𝐞 𝐬𝐞𝐫𝐢𝐨𝐮𝐬𝐥𝐲 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥 𝐨𝐟 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐝𝐮𝐞 𝐭𝐨 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒?

These two new preprints present findings supporting hypocortisolemia and the involvement of Epstein-Barr virus (EBV) and SARS-CoV-2 in ME/CFS and Long COVID.

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐚𝐧𝐝 𝐄𝐁𝐕 𝐢𝐧𝐯𝐨𝐥𝐯𝐞𝐦𝐞𝐧𝐭 𝐢𝐧 𝐌𝐄/𝐂𝐅𝐒: https://www.medrxiv.org/content/10.1101/2024.09.26.24314417v1.full-text

Healthrising link: https://www.healthrising.org/blog/2024/11/06/network-medicine-me-cfs-severely-ill/

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬, 𝐞𝐬𝐩𝐞𝐜𝐢𝐚𝐥𝐥𝐲 𝐭𝐡𝐞 𝐌𝐄/𝐂𝐅𝐒-𝐥𝐢𝐤𝐞 𝐩𝐡𝐞𝐧𝐨𝐭𝐲𝐩𝐞: https://www.medrxiv.org/content/10.1101/2024.11.07.24316777v1

𝐖𝐡𝐚𝐭'𝐬 𝐥𝐞𝐟𝐭 𝐭𝐨 𝐬𝐭𝐚𝐫𝐭 𝐭𝐫𝐞𝐚𝐭𝐢𝐧𝐠 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐚𝐧𝐭𝐢𝐯𝐢𝐫𝐚𝐥𝐬 𝐜𝐡𝐫𝐨𝐧𝐢𝐜𝐚𝐥𝐥𝐲 𝐚𝐧𝐝 𝐡𝐲𝐝𝐫𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐧𝐞 𝐢𝐧 𝐫𝐞𝐩𝐥𝐚𝐜𝐞𝐦𝐞𝐧𝐭 𝐝𝐨𝐬𝐞𝐬 i𝐧 𝐭𝐡𝐨𝐬𝐞 𝐰𝐢𝐭𝐡 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚?

𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡𝐢𝐧𝐠 𝐟𝐫𝐨𝐦 𝐚 𝐫𝐨𝐨𝐦
I am a patient of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) caused by Epstein-Barr virus (EBV) since 2013. It took away my medical career and left me home sick for years. Because of this, I decided to do research to better understand the disease I developed that few were studying at the time. I reviewed countless scientific articles because I had no other choice. My quality of life was so low, housebound, that I felt that if I did not find something to make me better, the suffering would lead me to consider suicide. Together with my ex-girlfriend, I developed a research proposal on the relationship between EBV and the development of ME/CFS in a subgroup of patients, and how HLA-II alleles might be involved. I sent hundreds of emails to research groups in Spain and abroad, but I only received a response from CIMA of the University of Navarra, from the great team of Dr. Bruno Paiva and Aintzane Zabaleta. They supported the hypothesis, and we collaborated in several review articles. Since before 2019, we already knew that ME/CFS was related to HLA-II alleles, especially because EBV infects by binding its glycoprotein gp-42 to HLA-II, and is related to several autoimmune diseases in people with HLA-II susceptible alleles.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐕𝐢𝐫𝐮𝐬 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐎𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐨𝐫 𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐅𝐚𝐭𝐢𝐠𝐮𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞” : https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.656797/full

Despite all this, I was ignored and ridiculed by patients and researchers alike. At first, many said that EBV could not cause ME/CFS, based on studies that did not classify patients according to the pathogen causing the disease, making it almost impossible to identify specific genetic variations of HLA-II in relation to pathogens.

When Long COVID came along, I tried to join patient and research groups to contribute and help, arguing that Long COVID was the same as ME/CFS. I was rebuffed, which was understandable, as no one wanted their disease to be related to ME/CFS, which was stigmatized as psychosomatic. Over time, many Long COVID patients were diagnosed with ME/CFS, meeting the same criteria. I warned that EBV reactivation would bring problems in these patients, just as it does in immunodeficiencies, and I was called crazy. Now it has been shown that EBV reactivation is implicated in Long COVID symptoms and the development of autoimmune diseases.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐯𝐢𝐫𝐮𝐬-𝐚𝐜𝐪𝐮𝐢𝐫𝐞𝐝 𝐢𝐦𝐦𝐮𝐧𝐨𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐢𝐧 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬-𝐈𝐬 𝐢𝐭 𝐩𝐫𝐞𝐬𝐞𝐧𝐭 𝐢𝐧 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?”:
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04515-7

I also mentioned that HLA-II alleles are key in the development of both diseases, as they are responsible for distinguishing between self and foreign in the body, and determine whether or not the immune response is effective against a pathogen. However, I continued to be ignored. We recently published on the connection between ME/CFS, Long COVID and ASIA syndrome, which includes post-vaccine syndromes, again highlighting the role of HLA-II alleles. ASIA syndromes, which include post-vaccine syndromes and immune checkpoint inhibitor (ICI)-associated hypophysitis, have been linked to HLA-II alleles because of the exaggerated responses they generate. Despite this, I continued to receive ridicule in forums, as some do not consider ASIA syndrome as a valid disease, despite scientific evidence, such as the connection of hypophysitis generated by ICIs with HLA-II alleles.

“𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐀𝐒𝐈𝐀: 𝐚 𝐯𝐚𝐜𝐜𝐢𝐧𝐞- 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐛𝐞𝐡𝐢𝐧𝐝 𝐭𝐡𝐞 𝐨𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬.”
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

Just after publishing this article, my father was diagnosed with bladder cancer and treated with ICIs. Predictably, he developed autoimmune hypophysitis because he possesses the DR-15 allele, just as I do. This same allele was responsible for my autoimmune hypophysitis in 2013 and subsequent development of ME/CFS. What do I say to those who deny the existence of ASIA syndrome, that my father made it up? If he had not insisted on having his cortisol levels checked, he would have died, as routine testing with ICIs does not include this check.

Literature reviews are continually discredited and downplayed, when in fact they are fundamental to understanding that history repeats itself, and that what we believe to be a new disease is not so new. You don't have to go far to see that SARS-CoV, first cousin of SARS-CoV-2, also caused similar problems to Long COVID in a part of the population that got infected, such as the development of autoimmune hypophysitis, hypocortisolism and the same symptoms as ME/CFS and Long COVID.

𝐀𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐨𝐧 𝐞𝐚𝐫𝐥𝐲 𝐒𝐀𝐑𝐒-𝐂𝐨𝐕 𝐝𝐨𝐜𝐮𝐦𝐞𝐧𝐭𝐢𝐧𝐠 𝐜𝐚𝐬𝐞𝐬 𝐨𝐟 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐢𝐧 𝟑𝟗% 𝐨𝐟 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐬𝐭𝐮𝐝𝐢𝐞𝐝:
https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2005.02325.x
https://www.sciencedirect.com/science/article/pii/S0306987704002828?via%3Dihub

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐡𝐚𝐩𝐩𝐞𝐧𝐢𝐧𝐠 𝐰𝐢𝐭𝐡 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?
The same thing that has happened with many other autoimmune diseases such as multiple sclerosis, lupus or rheumatoid arthritis. It has taken decades to show that behind the immune hyperactivity they present, there was a persistent pathogen and a genetic susceptibility linked to HLA-II.

Finally, an article has come to light that gives me peace of mind, because after so much rejection and scorn, science is confirming the objective relationships between the development of Long COVID, ME/CFS and HLA-II alleles.
https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1

𝐍𝐞𝐱𝐭 𝐩𝐨𝐢𝐧𝐭𝐬 𝐭𝐡𝐚𝐭 𝐈 𝐛𝐞𝐥𝐢𝐞𝐯𝐞 𝐰𝐢𝐥𝐥 𝐛𝐞 𝐜𝐨𝐧𝐟𝐢𝐫𝐦𝐞𝐝:
Patients with susceptible HLA-II alleles do not achieve effective control of SARS-CoV-2 in Long COVID nor EBV in ME/CFS.
Hypocortisolism in these patients is caused by autoimmune hypophysitis or damage to the hypothalamus, related to HLA-II alleles.
Hypocortisolism, by promoting immune hyperactivation, perpetuates immune exhaustion in these diseases.
Hypocortisolism increases IFN-gamma levels, which increases MHC-II expression in antigen-presenting and non-antigen-presenting cells.
Both immune hyperactivity caused by persistent infection and increased MHC-II expression by IFN-gamma promote reactivations of EBV and other latent pathogens, as well as the formation of neoantigens, which creates a favorable environment for the development of autoimmune diseases, as well as increasing the likelihood of formation of ectopic EBV lymphoid aggregates, which increases the likelihood of developing autoimmune diseases
In these diseases, chronic antivirals will be administered if no treatment can be found that completely eliminates the infection.
Hydrocortisone replacement will be prescribed to those with permanent pituitary damage.

I share all this to remember that, despite the difficulties or lack of support, it is important to keep going, because with time, truth and progress everything comes to light, proving that you were not crazy, as many believed.

Also, some people think that I have received money for my work, but I want to clarify that during all these years of research I have not received a penny. My only motivation has been to contribute to research. I have done everything from a room with a computer, since I have not yet finished my degree and I have no income and no home of my own.

I wish I had not gotten sick in the middle of my medical career, but later, so that I could have helped more and things would have come out sooner. And I hope we have more economic resources to continue with this line of research.

A hug to all of you and keep going. And I would also like to thank that without the Ramsay Award Program 2019 of Solve ME/CFS Initiative and without the team of Dr. Bruno Paiva and Aintzane Zabaleta from CIMA of the University of Navarra I would not have been able to improve or advance in this hypothesis.

 

[Aidan Walsh]

View attachment 54790
𝐖𝐡𝐚𝐭 𝐦𝐨𝐫𝐞 𝐢𝐬 𝐧𝐞𝐞𝐝𝐞𝐝 𝐭𝐨 𝐭𝐚𝐤𝐞 𝐬𝐞𝐫𝐢𝐨𝐮𝐬𝐥𝐲 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥 𝐨𝐟 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐝𝐮𝐞 𝐭𝐨 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒?

These two new preprints present findings supporting hypocortisolemia and the involvement of Epstein-Barr virus (EBV) and SARS-CoV-2 in ME/CFS and Long COVID.

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐚𝐧𝐝 𝐄𝐁𝐕 𝐢𝐧𝐯𝐨𝐥𝐯𝐞𝐦𝐞𝐧𝐭 𝐢𝐧 𝐌𝐄/𝐂𝐅𝐒: https://www.medrxiv.org/content/10.1101/2024.09.26.24314417v1.full-text

Healthrising link: https://www.healthrising.org/blog/2024/11/06/network-medicine-me-cfs-severely-ill/

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬, 𝐞𝐬𝐩𝐞𝐜𝐢𝐚𝐥𝐥𝐲 𝐭𝐡𝐞 𝐌𝐄/𝐂𝐅𝐒-𝐥𝐢𝐤𝐞 𝐩𝐡𝐞𝐧𝐨𝐭𝐲𝐩𝐞: https://www.medrxiv.org/content/10.1101/2024.11.07.24316777v1

𝐖𝐡𝐚𝐭'𝐬 𝐥𝐞𝐟𝐭 𝐭𝐨 𝐬𝐭𝐚𝐫𝐭 𝐭𝐫𝐞𝐚𝐭𝐢𝐧𝐠 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐚𝐧𝐭𝐢𝐯𝐢𝐫𝐚𝐥𝐬 𝐜𝐡𝐫𝐨𝐧𝐢𝐜𝐚𝐥𝐥𝐲 𝐚𝐧𝐝 𝐡𝐲𝐝𝐫𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐧𝐞 𝐢𝐧 𝐫𝐞𝐩𝐥𝐚𝐜𝐞𝐦𝐞𝐧𝐭 𝐝𝐨𝐬𝐞𝐬 i𝐧 𝐭𝐡𝐨𝐬𝐞 𝐰𝐢𝐭𝐡 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚?

𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡𝐢𝐧𝐠 𝐟𝐫𝐨𝐦 𝐚 𝐫𝐨𝐨𝐦
I am a patient of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) caused by Epstein-Barr virus (EBV) since 2013. It took away my medical career and left me home sick for years. Because of this, I decided to do research to better understand the disease I developed that few were studying at the time. I reviewed countless scientific articles because I had no other choice. My quality of life was so low, housebound, that I felt that if I did not find something to make me better, the suffering would lead me to consider suicide. Together with my ex-girlfriend, I developed a research proposal on the relationship between EBV and the development of ME/CFS in a subgroup of patients, and how HLA-II alleles might be involved. I sent hundreds of emails to research groups in Spain and abroad, but I only received a response from CIMA of the University of Navarra, from the great team of Dr. Bruno Paiva and Aintzane Zabaleta. They supported the hypothesis, and we collaborated in several review articles. Since before 2019, we already knew that ME/CFS was related to HLA-II alleles, especially because EBV infects by binding its glycoprotein gp-42 to HLA-II, and is related to several autoimmune diseases in people with HLA-II susceptible alleles.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐕𝐢𝐫𝐮𝐬 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐎𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐨𝐫 𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐅𝐚𝐭𝐢𝐠𝐮𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞” : https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.656797/full

Despite all this, I was ignored and ridiculed by patients and researchers alike. At first, many said that EBV could not cause ME/CFS, based on studies that did not classify patients according to the pathogen causing the disease, making it almost impossible to identify specific genetic variations of HLA-II in relation to pathogens.

When Long COVID came along, I tried to join patient and research groups to contribute and help, arguing that Long COVID was the same as ME/CFS. I was rebuffed, which was understandable, as no one wanted their disease to be related to ME/CFS, which was stigmatized as psychosomatic. Over time, many Long COVID patients were diagnosed with ME/CFS, meeting the same criteria. I warned that EBV reactivation would bring problems in these patients, just as it does in immunodeficiencies, and I was called crazy. Now it has been shown that EBV reactivation is implicated in Long COVID symptoms and the development of autoimmune diseases.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐯𝐢𝐫𝐮𝐬-𝐚𝐜𝐪𝐮𝐢𝐫𝐞𝐝 𝐢𝐦𝐦𝐮𝐧𝐨𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐢𝐧 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬-𝐈𝐬 𝐢𝐭 𝐩𝐫𝐞𝐬𝐞𝐧𝐭 𝐢𝐧 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?”:
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04515-7

I also mentioned that HLA-II alleles are key in the development of both diseases, as they are responsible for distinguishing between self and foreign in the body, and determine whether or not the immune response is effective against a pathogen. However, I continued to be ignored. We recently published on the connection between ME/CFS, Long COVID and ASIA syndrome, which includes post-vaccine syndromes, again highlighting the role of HLA-II alleles. ASIA syndromes, which include post-vaccine syndromes and immune checkpoint inhibitor (ICI)-associated hypophysitis, have been linked to HLA-II alleles because of the exaggerated responses they generate. Despite this, I continued to receive ridicule in forums, as some do not consider ASIA syndrome as a valid disease, despite scientific evidence, such as the connection of hypophysitis generated by ICIs with HLA-II alleles.

“𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐀𝐒𝐈𝐀: 𝐚 𝐯𝐚𝐜𝐜𝐢𝐧𝐞- 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐛𝐞𝐡𝐢𝐧𝐝 𝐭𝐡𝐞 𝐨𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬.”
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

Just after publishing this article, my father was diagnosed with bladder cancer and treated with ICIs. Predictably, he developed autoimmune hypophysitis because he possesses the DR-15 allele, just as I do. This same allele was responsible for my autoimmune hypophysitis in 2013 and subsequent development of ME/CFS. What do I say to those who deny the existence of ASIA syndrome, that my father made it up? If he had not insisted on having his cortisol levels checked, he would have died, as routine testing with ICIs does not include this check.

Literature reviews are continually discredited and downplayed, when in fact they are fundamental to understanding that history repeats itself, and that what we believe to be a new disease is not so new. You don't have to go far to see that SARS-CoV, first cousin of SARS-CoV-2, also caused similar problems to Long COVID in a part of the population that got infected, such as the development of autoimmune hypophysitis, hypocortisolism and the same symptoms as ME/CFS and Long COVID.

𝐀𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐨𝐧 𝐞𝐚𝐫𝐥𝐲 𝐒𝐀𝐑𝐒-𝐂𝐨𝐕 𝐝𝐨𝐜𝐮𝐦𝐞𝐧𝐭𝐢𝐧𝐠 𝐜𝐚𝐬𝐞𝐬 𝐨𝐟 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐢𝐧 𝟑𝟗% 𝐨𝐟 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐬𝐭𝐮𝐝𝐢𝐞𝐝:
https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2005.02325.x
https://www.sciencedirect.com/science/article/pii/S0306987704002828?via%3Dihub

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐡𝐚𝐩𝐩𝐞𝐧𝐢𝐧𝐠 𝐰𝐢𝐭𝐡 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?
The same thing that has happened with many other autoimmune diseases such as multiple sclerosis, lupus or rheumatoid arthritis. It has taken decades to show that behind the immune hyperactivity they present, there was a persistent pathogen and a genetic susceptibility linked to HLA-II.

Finally, an article has come to light that gives me peace of mind, because after so much rejection and scorn, science is confirming the objective relationships between the development of Long COVID, ME/CFS and HLA-II alleles.
https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1

𝐍𝐞𝐱𝐭 𝐩𝐨𝐢𝐧𝐭𝐬 𝐭𝐡𝐚𝐭 𝐈 𝐛𝐞𝐥𝐢𝐞𝐯𝐞 𝐰𝐢𝐥𝐥 𝐛𝐞 𝐜𝐨𝐧𝐟𝐢𝐫𝐦𝐞𝐝:
Patients with susceptible HLA-II alleles do not achieve effective control of SARS-CoV-2 in Long COVID nor EBV in ME/CFS.
Hypocortisolism in these patients is caused by autoimmune hypophysitis or damage to the hypothalamus, related to HLA-II alleles.
Hypocortisolism, by promoting immune hyperactivation, perpetuates immune exhaustion in these diseases.
Hypocortisolism increases IFN-gamma levels, which increases MHC-II expression in antigen-presenting and non-antigen-presenting cells.
Both immune hyperactivity caused by persistent infection and increased MHC-II expression by IFN-gamma promote reactivations of EBV and other latent pathogens, as well as the formation of neoantigens, which creates a favorable environment for the development of autoimmune diseases, as well as increasing the likelihood of formation of ectopic EBV lymphoid aggregates, which increases the likelihood of developing autoimmune diseases
In these diseases, chronic antivirals will be administered if no treatment can be found that completely eliminates the infection.
Hydrocortisone replacement will be prescribed to those with permanent pituitary damage.

I share all this to remember that, despite the difficulties or lack of support, it is important to keep going, because with time, truth and progress everything comes to light, proving that you were not crazy, as many believed.

Also, some people think that I have received money for my work, but I want to clarify that during all these years of research I have not received a penny. My only motivation has been to contribute to research. I have done everything from a room with a computer, since I have not yet finished my degree and I have no income and no home of my own.

I wish I had not gotten sick in the middle of my medical career, but later, so that I could have helped more and things would have come out sooner. And I hope we have more economic resources to continue with this line of research.

A hug to all of you and keep going. And I would also like to thank that without the Ramsay Award Program 2019 of Solve ME/CFS Initiative and without the team of Dr. Bruno Paiva and Aintzane Zabaleta from CIMA of the University of Navarra I would not have been able to improve or advance in this hypothesis.

I was tested for Hypophystitis it was Negative, I have low Cortisol am in blood plus 24 hour urine collection samples. I also have a small 4mm pituitary tumor they said likely born with this not causing issues, it has never grown bigger either.

I had high pressure spinal fluid years ago went on 80mg of prednisone, it resolved. I took cortisol for am low 5 mg Cortef CFS never resolved but helped only some

 

[cfs since 1998]

View attachment 54790
𝐖𝐡𝐚𝐭 𝐦𝐨𝐫𝐞 𝐢𝐬 𝐧𝐞𝐞𝐝𝐞𝐝 𝐭𝐨 𝐭𝐚𝐤𝐞 𝐬𝐞𝐫𝐢𝐨𝐮𝐬𝐥𝐲 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥 𝐨𝐟 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐝𝐮𝐞 𝐭𝐨 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒?

These two new preprints present findings supporting hypocortisolemia and the involvement of Epstein-Barr virus (EBV) and SARS-CoV-2 in ME/CFS and Long COVID.

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐚𝐧𝐝 𝐄𝐁𝐕 𝐢𝐧𝐯𝐨𝐥𝐯𝐞𝐦𝐞𝐧𝐭 𝐢𝐧 𝐌𝐄/𝐂𝐅𝐒: https://www.medrxiv.org/content/10.1101/2024.09.26.24314417v1.full-text

Healthrising link: https://www.healthrising.org/blog/2024/11/06/network-medicine-me-cfs-severely-ill/

𝐌𝐨𝐫𝐧𝐢𝐧𝐠 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐢𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬, 𝐞𝐬𝐩𝐞𝐜𝐢𝐚𝐥𝐥𝐲 𝐭𝐡𝐞 𝐌𝐄/𝐂𝐅𝐒-𝐥𝐢𝐤𝐞 𝐩𝐡𝐞𝐧𝐨𝐭𝐲𝐩𝐞: https://www.medrxiv.org/content/10.1101/2024.11.07.24316777v1

𝐖𝐡𝐚𝐭'𝐬 𝐥𝐞𝐟𝐭 𝐭𝐨 𝐬𝐭𝐚𝐫𝐭 𝐭𝐫𝐞𝐚𝐭𝐢𝐧𝐠 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐚𝐧𝐭𝐢𝐯𝐢𝐫𝐚𝐥𝐬 𝐜𝐡𝐫𝐨𝐧𝐢𝐜𝐚𝐥𝐥𝐲 𝐚𝐧𝐝 𝐡𝐲𝐝𝐫𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐧𝐞 𝐢𝐧 𝐫𝐞𝐩𝐥𝐚𝐜𝐞𝐦𝐞𝐧𝐭 𝐝𝐨𝐬𝐞𝐬 i𝐧 𝐭𝐡𝐨𝐬𝐞 𝐰𝐢𝐭𝐡 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚?

𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡𝐢𝐧𝐠 𝐟𝐫𝐨𝐦 𝐚 𝐫𝐨𝐨𝐦
I am a patient of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) caused by Epstein-Barr virus (EBV) since 2013. It took away my medical career and left me home sick for years. Because of this, I decided to do research to better understand the disease I developed that few were studying at the time. I reviewed countless scientific articles because I had no other choice. My quality of life was so low, housebound, that I felt that if I did not find something to make me better, the suffering would lead me to consider suicide. Together with my ex-girlfriend, I developed a research proposal on the relationship between EBV and the development of ME/CFS in a subgroup of patients, and how HLA-II alleles might be involved. I sent hundreds of emails to research groups in Spain and abroad, but I only received a response from CIMA of the University of Navarra, from the great team of Dr. Bruno Paiva and Aintzane Zabaleta. They supported the hypothesis, and we collaborated in several review articles. Since before 2019, we already knew that ME/CFS was related to HLA-II alleles, especially because EBV infects by binding its glycoprotein gp-42 to HLA-II, and is related to several autoimmune diseases in people with HLA-II susceptible alleles.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐕𝐢𝐫𝐮𝐬 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐎𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐨𝐫 𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐅𝐚𝐭𝐢𝐠𝐮𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞” : https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.656797/full

Despite all this, I was ignored and ridiculed by patients and researchers alike. At first, many said that EBV could not cause ME/CFS, based on studies that did not classify patients according to the pathogen causing the disease, making it almost impossible to identify specific genetic variations of HLA-II in relation to pathogens.

When Long COVID came along, I tried to join patient and research groups to contribute and help, arguing that Long COVID was the same as ME/CFS. I was rebuffed, which was understandable, as no one wanted their disease to be related to ME/CFS, which was stigmatized as psychosomatic. Over time, many Long COVID patients were diagnosed with ME/CFS, meeting the same criteria. I warned that EBV reactivation would bring problems in these patients, just as it does in immunodeficiencies, and I was called crazy. Now it has been shown that EBV reactivation is implicated in Long COVID symptoms and the development of autoimmune diseases.

“𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐯𝐢𝐫𝐮𝐬-𝐚𝐜𝐪𝐮𝐢𝐫𝐞𝐝 𝐢𝐦𝐦𝐮𝐧𝐨𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐢𝐧 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬-𝐈𝐬 𝐢𝐭 𝐩𝐫𝐞𝐬𝐞𝐧𝐭 𝐢𝐧 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?”:
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04515-7

I also mentioned that HLA-II alleles are key in the development of both diseases, as they are responsible for distinguishing between self and foreign in the body, and determine whether or not the immune response is effective against a pathogen. However, I continued to be ignored. We recently published on the connection between ME/CFS, Long COVID and ASIA syndrome, which includes post-vaccine syndromes, again highlighting the role of HLA-II alleles. ASIA syndromes, which include post-vaccine syndromes and immune checkpoint inhibitor (ICI)-associated hypophysitis, have been linked to HLA-II alleles because of the exaggerated responses they generate. Despite this, I continued to receive ridicule in forums, as some do not consider ASIA syndrome as a valid disease, despite scientific evidence, such as the connection of hypophysitis generated by ICIs with HLA-II alleles.

“𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐀𝐒𝐈𝐀: 𝐚 𝐯𝐚𝐜𝐜𝐢𝐧𝐞- 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐛𝐞𝐡𝐢𝐧𝐝 𝐭𝐡𝐞 𝐨𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬.”
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full

Just after publishing this article, my father was diagnosed with bladder cancer and treated with ICIs. Predictably, he developed autoimmune hypophysitis because he possesses the DR-15 allele, just as I do. This same allele was responsible for my autoimmune hypophysitis in 2013 and subsequent development of ME/CFS. What do I say to those who deny the existence of ASIA syndrome, that my father made it up? If he had not insisted on having his cortisol levels checked, he would have died, as routine testing with ICIs does not include this check.

Literature reviews are continually discredited and downplayed, when in fact they are fundamental to understanding that history repeats itself, and that what we believe to be a new disease is not so new. You don't have to go far to see that SARS-CoV, first cousin of SARS-CoV-2, also caused similar problems to Long COVID in a part of the population that got infected, such as the development of autoimmune hypophysitis, hypocortisolism and the same symptoms as ME/CFS and Long COVID.

𝐀𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐨𝐧 𝐞𝐚𝐫𝐥𝐲 𝐒𝐀𝐑𝐒-𝐂𝐨𝐕 𝐝𝐨𝐜𝐮𝐦𝐞𝐧𝐭𝐢𝐧𝐠 𝐜𝐚𝐬𝐞𝐬 𝐨𝐟 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 𝐢𝐧 𝟑𝟗% 𝐨𝐟 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐬𝐭𝐮𝐝𝐢𝐞𝐝:
https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2005.02325.x
https://www.sciencedirect.com/science/article/pii/S0306987704002828?via%3Dihub

𝐖𝐡𝐚𝐭 𝐢𝐬 𝐡𝐚𝐩𝐩𝐞𝐧𝐢𝐧𝐠 𝐰𝐢𝐭𝐡 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?
The same thing that has happened with many other autoimmune diseases such as multiple sclerosis, lupus or rheumatoid arthritis. It has taken decades to show that behind the immune hyperactivity they present, there was a persistent pathogen and a genetic susceptibility linked to HLA-II.

Finally, an article has come to light that gives me peace of mind, because after so much rejection and scorn, science is confirming the objective relationships between the development of Long COVID, ME/CFS and HLA-II alleles.
https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1

𝐍𝐞𝐱𝐭 𝐩𝐨𝐢𝐧𝐭𝐬 𝐭𝐡𝐚𝐭 𝐈 𝐛𝐞𝐥𝐢𝐞𝐯𝐞 𝐰𝐢𝐥𝐥 𝐛𝐞 𝐜𝐨𝐧𝐟𝐢𝐫𝐦𝐞𝐝:
Patients with susceptible HLA-II alleles do not achieve effective control of SARS-CoV-2 in Long COVID nor EBV in ME/CFS.
Hypocortisolism in these patients is caused by autoimmune hypophysitis or damage to the hypothalamus, related to HLA-II alleles.
Hypocortisolism, by promoting immune hyperactivation, perpetuates immune exhaustion in these diseases.
Hypocortisolism increases IFN-gamma levels, which increases MHC-II expression in antigen-presenting and non-antigen-presenting cells.
Both immune hyperactivity caused by persistent infection and increased MHC-II expression by IFN-gamma promote reactivations of EBV and other latent pathogens, as well as the formation of neoantigens, which creates a favorable environment for the development of autoimmune diseases, as well as increasing the likelihood of formation of ectopic EBV lymphoid aggregates, which increases the likelihood of developing autoimmune diseases
In these diseases, chronic antivirals will be administered if no treatment can be found that completely eliminates the infection.
Hydrocortisone replacement will be prescribed to those with permanent pituitary damage.

I share all this to remember that, despite the difficulties or lack of support, it is important to keep going, because with time, truth and progress everything comes to light, proving that you were not crazy, as many believed.

Also, some people think that I have received money for my work, but I want to clarify that during all these years of research I have not received a penny. My only motivation has been to contribute to research. I have done everything from a room with a computer, since I have not yet finished my degree and I have no income and no home of my own.

I wish I had not gotten sick in the middle of my medical career, but later, so that I could have helped more and things would have come out sooner. And I hope we have more economic resources to continue with this line of research.

A hug to all of you and keep going. And I would also like to thank that without the Ramsay Award Program 2019 of Solve ME/CFS Initiative and without the team of Dr. Bruno Paiva and Aintzane Zabaleta from CIMA of the University of Navarra I would not have been able to improve or advance in this hypothesis.

I agree that science needs to look at EBV, considering that EBV is now conclusively linked to multiple sclerosis, and may have an important role in other autoimmune diseases including RA, Sjogren's, and lupus. I am currently working on a persuasive essay on this topic.

The problem is some of us have gotten worse with antivirals, in some cases a lot worse. I myself and a few others developed small fiber neuropathy pretty rapidly after starting valacyclovir. Do you have a theory for that?

 

[Violeta]

I agree that science needs to look at EBV, considering that EBV is now conclusively linked to multiple sclerosis, and may have an important role in other autoimmune diseases including RA, Sjogren's, and lupus. I am currently working on a persuasive essay on this topic.

The problem is some of us have gotten worse with antivirals, in some cases a lot worse. I myself and a few others developed small fiber neuropathy pretty rapidly after starting valacyclovir. Do you have a theory for that?

I found this about valacyclovir.

"Some people with a weak immune system who take valacyclovir may develop a condition called thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). These conditions can cause small blood clots throughout the body, reducing blood flow to organs like the brain, heart, and kidneys."

Do small blood clots cause small fiber neuropathy?

 

[cfs since 1998]

I found this about valacyclovir.

"Some people with a weak immune system who take valacyclovir may develop a condition called thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). These conditions can cause small blood clots throughout the body, reducing blood flow to organs like the brain, heart, and kidneys."

Do small blood clots cause small fiber neuropathy?

Maybe, but the other symptoms don't match TTP or HUS very well. Thank you for pointing this out though, I will look more closely at these.

 

[Manuel]

𝐈𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐜𝐞 𝐨𝐟 𝐭𝐡𝐞 𝐬𝐚𝐥𝐢𝐯𝐚 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐜𝐮𝐫𝐯𝐞 𝐟𝐨𝐫 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒..

𝐖𝐡𝐲 𝐩𝐞𝐫𝐟𝐨𝐫𝐦 𝐢𝐭?
The blood cortisol tests I had done in the morning (at 11 o'clock) always came out within normal ranges, even after the EBV-caused hypophysitis I had at the onset of my disease in 2013. However, these values 𝐝𝐨 𝐧𝐨𝐭 𝐫𝐞𝐟𝐥𝐞𝐜𝐭 𝐭𝐡𝐞 𝐚𝐜𝐭𝐮𝐚𝐥 𝐥𝐞𝐯𝐞𝐥 𝐰𝐡𝐞𝐧 𝐈 𝐰𝐨𝐤𝐞 𝐮𝐩, since, by the time I got to the blood draw, it had been a while since I woke up.

In contrast, the saliva cortisol test 𝐝𝐨𝐞𝐬 𝐚𝐥𝐥𝐨𝐰 𝐲𝐨𝐮 𝐭𝐨 𝐦𝐞𝐚𝐬𝐮𝐫𝐞 𝐭𝐡𝐞 𝐥𝐞𝐯𝐞𝐥 𝐣𝐮𝐬𝐭 𝐚𝐟𝐭𝐞𝐫 𝐰𝐚𝐤𝐢𝐧𝐠 𝐮𝐩, because you can take the sample directly in bed, before starting any activity. This gives a more accurate picture of the circadian rhythm.

𝐀𝐝𝐯𝐚𝐧𝐭𝐚𝐠𝐞𝐬 𝐨𝐟 𝐬𝐚𝐥𝐢𝐯𝐚 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥
You can take the samples comfortably from home.
Allows cortisol to be measured at different times of the day, giving a complete picture of the 𝐜𝐢𝐫𝐜𝐚𝐝𝐢𝐚𝐧 𝐫𝐡𝐲𝐭𝐡𝐦.
Measures free, metabolically active 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥, rather than the total cortisol usually measured in blood.
A single morning blood cortisol sample does not accurately reflect the full circadian rhythm.

𝐁𝐨𝐭𝐭𝐨𝐦 𝐥𝐢𝐧𝐞:
The morning peak cortisol should be normal. In my case, it is well below expected, something that is also seen in many studies on Long COVID and ME/CFS.

𝐖𝐡𝐚𝐭 𝐭𝐨 𝐝𝐨 𝐢𝐟 𝐲𝐨𝐮 𝐡𝐚𝐯𝐞 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐨𝐫 𝐌𝐄/𝐂𝐅𝐒?
Perform this test to confirm possible hormone deficiencies.
If the cortisol curve is low, your endocrinologist should order a 𝐂𝐑𝐇 𝐨𝐫 𝐢𝐧𝐬𝐮𝐥𝐢𝐧 𝐬𝐭𝐢𝐦𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐭𝐞𝐬𝐭 in the hospital to assess pituitary function and ACTH secretion.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧!
With other 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 and 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬, so that more people know the importance of this test and benefit from a more accurate diagnosis.

https://x.com/manruipa/status/1857416405819232631

 

[Manuel]

𝐖𝐞 𝐢𝐧𝐯𝐢𝐭𝐞 𝐲𝐨𝐮 𝐭𝐨 𝐫𝐞𝐚𝐝 𝐭𝐡𝐢𝐬 𝐢𝐧𝐜𝐫𝐞𝐝𝐢𝐛𝐥𝐞 𝐫𝐞𝐯𝐢𝐞𝐰 𝐛𝐲 𝐂𝐨𝐫𝐭 𝐉𝐨𝐡𝐧𝐬𝐨𝐧!

In this summary, Cort Johnson explores several articles, including ours:

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

In his analysis, he highlights how two different perspectives converge in a central conclusion: the crucial role of the pituitary gland in these conditions. Both could be a consequence of persistent infection.

𝐇𝐢𝐠𝐡𝐥𝐢𝐠𝐡𝐭𝐬:
𝐎𝐮𝐫 𝐚𝐩𝐩𝐫𝐨𝐚𝐜𝐡: autoimmune damage to the pituitary, possibly caused by persistent infections, is key to hormonal deficiencies, especially ACTH, leading to hypocortisolemia.

𝐀𝐧𝐨𝐭𝐡𝐞𝐫 𝐚𝐩𝐩𝐫𝐨𝐚𝐜𝐡: elevated intracranial hypertension can damage the pituitary, generating similar hormonal deficiencies.

𝐒𝐡𝐚𝐫𝐞𝐝 𝐜𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧: the pituitary plays a crucial role in the development of 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐌𝐄/𝐂𝐅𝐒, underlining the importance of addressing these dysfunctions.

This analysis shows how different research can complement each other to improve our understanding of these pathologies.

𝐃𝐨𝐧'𝐭 𝐦𝐢𝐬𝐬 𝐢𝐭!
Link to Cort Johnson's summary: https://www.healthrising.org/blog/2024/11/14/exhausted_immune-t-cells-chronic-fatigue-syndrome/

 

[Violeta]

Cort does really good reviews.

And thank you, Manuel, for keeping us up to date on this.

 

[Oliver3]

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.

Definitely not a myopic view. This should never have been given to young people. Ever!
Fine people in older age groups or at risks categories take the chance. There's still no real evidence that they actually saved lives?
Why? Well it's not called COVID 19 for any old reason is it. This was around in the UK I at least December 2019. Confirmed everyone in my hoe town came down with a nasty " flu" with a dry cough.blood draw Nurses have since today ne it was COVID 19. If you remember the incessant tracking of numbers for a whole year n more...telling us about 100,000 cases on this day , 45 ,000 on that....this went on a year before any vaccines were put in arms. ( And that's only the people who bothered to get tested)
Virtually everyone was exposed to some degree to the virus in my opinion before the whole vaccine schedule has been swung into action.
You NEEDED to get the infection
You needed long term immunity.
This whole thing has been an utter debate and I so angry about it.

I' get my blood drawn often enough and the nurse that does mine was a front line COVID nurse in the NHS during the pandemic ( she had enough of seeing the whole thing).

She told me after vaccines were administered still births , strokes Nnd heart attacks skyrocketed


She said that they also started feeding d dimed info into the system on request of the government. It got to a point where every young person who came into a and e , no matter what the illness , were screened routinely
That feedback led to Astra zeneca being puked

She also said the suicide rate, particularly amongst teenagers due too lockdown was horrendous.

Anybody denying this aspect now, well it's either being blind deliberately or just blind and.....

Thinking about vaccines being a cause of autoimmunity is nothing new is it ( 1986 legislation in America to grant legal indemnity is proof of that isn't it) but I wonder if one of the reasons m.e
Research is constantly not funded is that the roads to a cause are gonna lead in a big way to a big causal factor in m.e.


I used to think modern medicine was phenomenal. It still is
But it's arrogance and vested interests are creating chimera.
The Amish did just fine during the pandemic. I don't know anyone who died of COVID but I know of one death and many many vascular injuries definitely caused by the vaccines.

Honestly I can't help but vent as I'm appalled by people refusing to believe what is in front of them

 

[Manuel]

𝐀𝐧𝐨𝐭𝐡𝐞𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞 𝐬𝐡𝐨𝐰𝐢𝐧𝐠 𝐡𝐨𝐰 𝐡𝐲𝐩𝐨𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐢𝐬𝐦 𝐜𝐨𝐮𝐥𝐝 𝐛𝐞 𝐭𝐡𝐞 𝐤𝐞𝐲 𝐭𝐨 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃.

“Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the “Long COVID syndrome”.

https://link.springer.com/article/10.1007/s11102-024-01463-3

If you are an ME/CFS or Long COVID patient, share this post and take this list of markers to your endocrinologist to assess for the presence of secondary adrenal insufficiency:

𝐁𝐚𝐬𝐞𝐥𝐢𝐧𝐞 𝐭𝐞𝐬𝐭𝐬:
Morning serum cortisol (7-9 am).
Basal plasma ACTH (7-9 am).
24h saliva cortisol (4 samples in 24h): Useful in cases of mild hypocortisolism, where ACTH and cortisol levels in blood may be normal in the morning.
24h urine free cortisol.
DHEA-S.
Androstenedione.
Aldosterone and plasma renin (rule out primary adrenal insufficiency).

𝐃𝐲𝐧𝐚𝐦𝐢𝐜 𝐭𝐞𝐬𝐭𝐬:
Synacthen test (ACTH stimulation): to rule out primary adrenal insufficiency.
Insulin tolerance test (ITP): To assess secondary adrenal insufficiency, although it is more invasive and has a higher risk of side effects (hypoglycemia).
CRH stimulation: Differentiates between primary and secondary adrenal insufficiency, more useful in secondary/tertiary cases.
Methyrapone test: Detects secondary adrenal insufficiency, is more physiologic than insulin test and with fewer side effects.

𝐈𝐦𝐚𝐠𝐢𝐧𝐠 𝐭𝐞𝐬𝐭𝐬:
Pituitary MRI with contrast.
Adrenal CT (if ACTH is high).

𝐈𝐧𝐝𝐢𝐫𝐞𝐜𝐭 𝐦𝐚𝐫𝐤𝐞𝐫𝐬:
Serum 17-hydroxyprogesterone.
Primary: Elevated.
Secondary: Low or normal.
Serum electrolytes (sodium, potassium).
Primary: Hyponatremia and hyperkalemia.
Secondary: Normal.
Glycemia (associated hypoglycemia).
Primary: Low.
Secondary: May be normal.
Serum prolactin (pituitary stalk disorders).

 

[Manuel]

𝐀𝐧𝐨𝐭𝐡𝐞𝐫 𝐧𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞 𝐬𝐡𝐨𝐰𝐢𝐧𝐠 𝐭𝐡𝐞 𝐠𝐫𝐞𝐚𝐭 𝐬𝐢𝐦𝐢𝐥𝐚𝐫𝐢𝐭𝐲 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃.

Years ago, when we said that Myalgic Encephalomyelitis(ME/CFS) had an infectious origin, many researchers and patients rejected this theory. However, it is now gaining strength. Even the similarity between Myalgic Encephalomyelitis and Long COVID was also rejected.

This new article provides further evidence of the similarity between Myalgic Encephalomyelitis and Long COVID. It demonstrates that immune exhaustion occurs in both pathologies and that persistent infection is responsible.

The article raises the 𝐟𝐨𝐥𝐥𝐨𝐰𝐢𝐧𝐠 𝐪𝐮𝐞𝐬𝐭𝐢𝐨𝐧𝐬, which I will answer based on what we currently know from our reviews:

𝐖𝐡𝐚𝐭 𝐚𝐫𝐞 𝐭𝐡𝐞 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬 𝐜𝐚𝐮𝐬𝐢𝐧𝐠 𝐭𝐡𝐞 𝐢𝐧𝐢𝐭𝐢𝐚𝐥 𝐩𝐫𝐢𝐦𝐢𝐧𝐠 𝐞𝐯𝐞𝐧𝐭, 𝐚𝐧𝐝 𝐚𝐫𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭 𝐓 𝐜𝐞𝐥𝐥 𝐜𝐥𝐨𝐧𝐨𝐭𝐲𝐩𝐞𝐬 𝐚𝐥𝐭𝐞𝐫𝐞𝐝 𝐢𝐧 𝐌𝐄?

Any uncontrolled infection in an individual with HLA-II alleles deficient against that infection.

𝐀𝐫𝐞 𝐦𝐞𝐦𝐛𝐞𝐫𝐬 𝐨𝐟 𝐚 𝐬𝐢𝐧𝐠𝐥𝐞 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧 𝐟𝐚𝐦𝐢𝐥𝐲 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐢𝐛𝐥𝐞 𝐟𝐨𝐫 𝐭𝐡𝐞 𝐨𝐧𝐬𝐞𝐭 𝐨𝐟 𝐌𝐄, 𝐨𝐫 𝐜𝐚𝐧 𝐦𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬 𝐢𝐧𝐜𝐢𝐭𝐞 𝐭𝐡𝐞 𝐢𝐥𝐥𝐧𝐞𝐬𝐬?

Any intracellular pathogen (viruses, bacteria or parasites). Herpesviruses are most associated with the development of ME/CFS because of their ability to generate latency and because some, such as Epstein-Barr virus, infect by binding to HLA-II molecules.

𝐈𝐬 𝐭𝐡𝐞𝐫𝐞 𝐚 𝐫𝐨𝐥𝐞 𝐨𝐟 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐡𝐞𝐫𝐩𝐞𝐬𝐯𝐢𝐫𝐮𝐬 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧𝐬 𝐨𝐫 𝐚𝐥𝐭𝐞𝐫𝐞𝐝 𝐚𝐜𝐭𝐢𝐯𝐢𝐭𝐲 𝐨𝐟 𝐞𝐧𝐝𝐨𝐠𝐞𝐧𝐨𝐮𝐬 𝐫𝐞𝐭𝐫𝐨𝐯𝐢𝐫𝐮𝐬𝐞𝐬?

Yes, as in any other immunodeficiency. Reactivations of latent pathogens, such as herpesviruses or Parvovirus B19, increase immune depletion and generate damage characteristic of these pathogens. They may even contribute to the development of autoimmune outbreaks.

𝐖𝐡𝐚𝐭 𝐜𝐨𝐧𝐝𝐢𝐭𝐢𝐨𝐧𝐬 𝐥𝐞𝐚𝐝 𝐭𝐨 𝐥𝐨𝐧𝐠-𝐭𝐞𝐫𝐦 𝐬𝐜𝐚𝐫𝐫𝐢𝐧𝐠 𝐨𝐟 𝐂𝐃𝟖+ 𝐓 𝐜𝐞𝐥𝐥𝐬 𝐚𝐧𝐝 𝐬𝐮𝐛𝐬𝐞𝐪𝐮𝐞𝐧𝐭𝐥𝐲 𝐜𝐨𝐧𝐭𝐫𝐢𝐛𝐮𝐭𝐞 𝐭𝐨 𝐌𝐄 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬?

Any persistent infection generates immune exhaustion of CD8 T cells due to chronic antigen persistence. Another key factor is the development of autoimmune diseases (such as autoimmune hypophysitis) as a consequence of infection. Autoimmune hypophysitis causes a cortisol deficit, which leads to increased immune hyperactivity and consequently aggravates immune exhaustion.

𝐚𝐧𝐝 𝐝𝐨 𝐝𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬 𝐞𝐦𝐩𝐥𝐨𝐲 𝐯𝐚𝐫𝐲𝐢𝐧𝐠 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦𝐬, 𝐭𝐡𝐞𝐫𝐞𝐛𝐲 𝐢𝐧𝐟𝐥𝐮𝐞𝐧𝐜𝐢𝐧𝐠 𝐭𝐡𝐞𝐢𝐫 𝐩𝐫𝐨𝐩𝐞𝐧𝐬𝐢𝐭𝐲 𝐭𝐨 𝐢𝐧𝐝𝐮𝐜𝐞 𝐓 𝐜𝐞𝐥𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧?

Exhaustion occurs primarily through chronic persistence of antigens in all of them. Each will have other pathways to evade the immune response.


𝐎𝐧 𝐩𝐫𝐨𝐩𝐨𝐬𝐞𝐝 𝐭𝐡𝐞𝐫𝐚𝐩𝐢𝐞𝐬:

We disagree with one of the treatments suggested in the article.
If infection were the sole cause of these pathologies, therapy with checkpoint inhibitors (CPIs) to decrease immune depletion might be useful. However:

This proposal does not take into account the autoimmunity present in these diseases, which also arises as a consequence of infection in patients with HLA-II alleles.

The use of ICIs in patients with autoimmune diseases increases the risk of aggravating autoimmunity, especially increasing the risk of autoimmune hypophysitis.

𝐖𝐡𝐚𝐭 𝐬𝐡𝐨𝐮𝐥𝐝 𝐛𝐞 𝐝𝐨𝐧𝐞?

Eliminate the underlying cause, i.e. persistent infection and the consequences of autoimmunities.
If viruses are the culprits, they should be treated chronically with antivirals until a therapy capable of completely eliminating them is developed.
Treat the consequences of developed autoimmunities. For example, if hypocortisolism is present, it should be treated with hydrocortisone in replacement doses (not supraphysiological doses that immunosuppress) to prevent immune hyperactivity.

𝐍𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: https://www.pnas.org/doi/epub/10.1073/pnas.2415119121

More information in X: https://x.com/manruipa/status/1864281296228213041

I attach in the thread more publications with information about the relationship between ME and Long COVID.





#LongCovid #MECFS #Health

 

[Manuel]

Recommendations for those patients with Long COVID, Myalgic Encephalomyelitis or post-vaccinal syndromes with hypocortisolism in the morning.

Many patients are afraid of the symptoms generated by corticosteroids in supraphysiological doses. Let us remember that in these diseases supraphysiologic doses would not be given but substitute doses as those produced by a healthy person.

Options before starting with full replacement doses of hydrocortisone:

Take doses of Panax ginseng that simulate the circadian rhythm of cortisol. It could be useful for those with mild hypocrotisolism.

If there is only mild hypocortisolism in the morning, one could take only low doses of hydrocortisone in the morning. When there have been years with mild hypocortisolism, the sensitivity of the glucocorticoid receptors can increase, causing that if the substitutive dose is given suddenly, it can generate symptoms. Therefore, in these cases the ideal is to first test the tolerance in the morning of 5mg of hydrocortisone. Some will find this dose sufficient to improve and others will need to continue to increase the dose up to a full replacement dose. This depends on the damage to the pituitary or adrenal gland.

Choose at the outset one of the two options and do not combine them. The combination of Panax ginseng and hydrocortisone should be done with care as both increase the effect of cortisol in the body. Therefore, if not done correctly, the combination can cause symptoms of hypercortisolism. Therefore, it is best to test tolerance separately to begin with and then decide whether to combine them. For example, one could treat with Panax ginseng in those who only take 5mg of hydrocortisone in the morning, to stimulate the afternoon cycle after the morning dose of hydrocortisone.

#LongCovid #MECFS #Health

Share this information with physicians and patients - it's time to better understand these conditions and their repercussions!

More information in X: https://x.com/manruipa/status/1868677757531472183

 

[Manuel]

𝐏𝐨𝐬𝐭𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐝𝐨𝐞𝐬 𝐍𝐎𝐓 𝐦𝐞𝐚𝐧 𝐲𝐨𝐮 𝐬𝐡𝐨𝐮𝐥𝐝 𝐛𝐞 𝐚𝐧𝐭𝐢𝐯𝐚𝐜𝐜𝐢𝐧𝐞!

Lately, there is a big buzz on networks about a new study that apparently “proves” that COVID-19 vaccines can cause post-vaccination syndromes in some patients. Predictably, many are using this as ammunition for anti-vaccine discourse. 𝐁𝐮𝐭 𝐭𝐡𝐞 𝐫𝐞𝐚𝐥𝐢𝐭𝐲 𝐢𝐬 𝐦𝐮𝐜𝐡 𝐦𝐨𝐫𝐞 𝐜𝐨𝐦𝐩𝐥𝐞𝐱 𝐚𝐧𝐝 𝐰𝐞 𝐡𝐚𝐝 𝐚𝐥𝐫𝐞𝐚𝐝𝐲 𝐰𝐚𝐫𝐧𝐞𝐝 𝐚𝐛𝐨𝐮𝐭 𝐭𝐡𝐢𝐬 𝐢𝐧 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥.

𝐓𝐡𝐞 𝐤𝐞𝐲 𝐢𝐬 𝐍𝐎𝐓 𝐭𝐡𝐞 𝐯𝐚𝐜𝐜𝐢𝐧𝐞, 𝐛𝐮𝐭 𝐡𝐨𝐰 𝐲𝐨𝐮𝐫 𝐢𝐦𝐦𝐮𝐧𝐞 𝐬𝐲𝐬𝐭𝐞𝐦 𝐫𝐞𝐬𝐩𝐨𝐧𝐝𝐬.

What these studies are showing is NOT that vaccines are “dangerous”, 𝐛𝐮𝐭 𝐭𝐡𝐚𝐭 𝐭𝐡𝐞𝐫𝐞 𝐚𝐫𝐞 𝐩𝐞𝐨𝐩𝐥𝐞 𝐰𝐢𝐭𝐡 𝐚 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐩𝐫𝐞𝐝𝐢𝐬𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧 𝐰𝐡𝐨 𝐨𝐯𝐞𝐫𝐫𝐞𝐚𝐜𝐭 𝐭𝐨 𝐜𝐞𝐫𝐭𝐚𝐢𝐧 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬, either by infection or vaccination. 𝐓𝐡𝐢𝐬 𝐢𝐬 𝐧𝐨𝐭 𝐧𝐞𝐰.

𝐏𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐡𝐚𝐯𝐞 𝐛𝐞𝐞𝐧 𝐚𝐫𝐨𝐮𝐧𝐝 𝐟𝐨𝐫 𝐝𝐞𝐜𝐚𝐝𝐞𝐬 𝐚𝐧𝐝 𝐡𝐚𝐯𝐞 𝐛𝐞𝐞𝐧 𝐝𝐞𝐬𝐜𝐫𝐢𝐛𝐞𝐝 𝐰𝐢𝐭𝐡𝐢𝐧 𝐭𝐡𝐞 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞/𝐀𝐝𝐣𝐮𝐯𝐚𝐧𝐭 𝐈𝐧𝐝𝐮𝐜𝐞𝐝 𝐈𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐀𝐒𝐈𝐀). Prior to COVID-19, similar syndromes had already been documented after vaccination against HPV, hepatitis B and even influenza.

𝐓𝐡𝐞 𝐫𝐞𝐚𝐬𝐨𝐧 𝐰𝐡𝐲 𝐬𝐨𝐦𝐞 𝐩𝐞𝐨𝐩𝐥𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩 𝐭𝐡𝐞𝐬𝐞 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬 𝐢𝐬 𝐧𝐨𝐭 𝐭𝐡𝐞 𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐢𝐭𝐬𝐞𝐥𝐟, 𝐛𝐮𝐭 𝐭𝐡𝐞𝐢𝐫 𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐬. If these same people had been infected with the virus, they probably would have developed the same pathology.

𝐎𝐮𝐫 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧𝐞𝐝 𝐢𝐭 𝐞𝐚𝐫𝐥𝐢𝐞𝐫: 𝐇𝐋𝐀-𝐈𝐈 𝐢𝐬 𝐭𝐡𝐞 𝐤𝐞𝐲.
Our model predicts that the predisposition to develop 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐜𝐟𝐬 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐥 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 depends on the combination of certain HLA-II alleles that determine how the immune system responds to the SARS-CoV-2 antigen. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full


𝐖𝐡𝐚𝐭 𝐡𝐚𝐩𝐩𝐞𝐧𝐬 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐚𝐥𝐥𝐲 𝐩𝐫𝐞𝐝𝐢𝐬𝐩𝐨𝐬𝐞𝐝 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐚𝐥𝐬?
𝐅𝐚𝐢𝐥𝐮𝐫𝐞 𝐨𝐟 𝐂𝐃𝟒 𝐓-𝐜𝐞𝐥𝐥 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧.
In individuals with certain HLA-II, CD4 T cells fail to efficiently control the immune response after contact with antigen (either virus or vaccine).
This generates an 𝐮𝐧𝐜𝐨𝐧𝐭𝐫𝐨𝐥𝐥𝐞𝐝 𝐞𝐱𝐩𝐚𝐧𝐬𝐢𝐨𝐧 𝐨𝐟 𝐂𝐃𝟖 𝐓 𝐜𝐞𝐥𝐥𝐬 in an attempt to compensate for the deficit.

𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐡𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐞𝐩𝐥𝐞𝐭𝐢𝐨𝐧
This dysregulated response leads to overproduction of antibodies and excessive CD8 T-cell activation.
Over time, CD8 T cells become exhausted, reducing the ability to control chronic infections.

𝐑𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐥𝐚𝐭𝐞𝐧𝐭 𝐯𝐢𝐫𝐮𝐬𝐞𝐬 𝐬𝐮𝐜𝐡 𝐚𝐬 𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐕𝐢𝐫𝐮𝐬 (𝐄𝐁𝐕)
The already weakened immune system cannot keep other viruses such as EBV or varicella-zoster virus (VZV) under control.
This results in symptoms of chronic fatigue, dysautonomia and neurological deterioration, as seen in Long COVID and myalgic encephalomyelitis.

𝐏𝐫𝐞𝐬𝐞𝐧𝐭𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐚𝐮𝐭𝐨𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 𝐚𝐧𝐝 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲.
As inflammation and the presence of viral antigens in tissues persist, the possibility of the immune system confusing these antigens with self proteins increases, generating autoimmunity.
This mechanism is similar to that observed in diseases such as multiple sclerosis or lupus following viral infections.

𝐖𝐡𝐚𝐭 𝐝𝐨 𝐭𝐡𝐞 𝐧𝐞𝐰 𝐬𝐭𝐮𝐝𝐢𝐞𝐬 𝐬𝐚𝐲? 𝐓𝐡𝐞𝐲 𝐯𝐚𝐥𝐢𝐝𝐚𝐭𝐞 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥.

Recently, 𝐭𝐡𝐞𝐬𝐞 𝐤𝐞𝐲 𝐬𝐭𝐮𝐝𝐢𝐞𝐬 𝐡𝐚𝐯𝐞 𝐜𝐨𝐧𝐟𝐢𝐫𝐦𝐞𝐝 𝐭𝐡𝐞 𝐩𝐢𝐥𝐥𝐚𝐫𝐬 𝐨𝐟 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥:

𝐓𝐡𝐞 𝐘𝐚𝐥𝐞 𝐭𝐞𝐚𝐦'𝐬 𝐩𝐫𝐞𝐩𝐫𝐢𝐧𝐭 𝐨𝐧 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐟𝐨𝐮𝐧𝐝:
Persistence of Spike protein in the blood of patients with postvaccinal symptoms.
Immune dysfunction with abnormal CD8 T-cell activation.
Reactivation of Epstein-Barr virus, a key marker of immune exhaustion.
https://www.medrxiv.org/content/10.1101/2025.02.18.25322379v1

𝐓𝐡𝐞 𝐬𝐭𝐮𝐝𝐲 𝐢𝐧 𝐍𝐚𝐭𝐮𝐫𝐞 𝐨𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐫𝐞𝐯𝐞𝐚𝐥𝐞𝐝:
Reduced cortisol levels, indicating dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, one of the central axes in our model.
CD8 T-cell expansion with progressive immune exhaustion.
EBV and VZV reactivation in patients with persistent symptoms.
https://www.nature.com/articles/s41586-023-06651-y

𝐏𝐍𝐀𝐒 𝐬𝐭𝐮𝐝𝐲 𝐨𝐧 𝐂𝐃𝟖 𝐓 𝐜𝐞𝐥𝐥 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧 𝐢𝐧 𝐌𝐒/𝐂𝐅𝐒 𝐫𝐞𝐯𝐞𝐚𝐥𝐞𝐝:
Transcriptional reprogramming predisposing CD8+ T cells towards exhaustion.
Elevated expression of exhaustion markers after exercise stimulus.
Correlation with chronic viral infections as a contributing factor in the pathogenesis of ME/CFS.
https://www.pnas.org/doi/10.1073/pnas.2415119121

𝐓𝐡𝐞 𝐫𝐞𝐯𝐢𝐞𝐰 𝐢𝐧 𝐉𝐨𝐮𝐫𝐧𝐚𝐥 𝐨𝐟 𝐈𝐦𝐦𝐮𝐧𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐒𝐜𝐢𝐞𝐧𝐜𝐞𝐬 𝐨𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐇𝐋𝐀:
Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID.
https://www.immunologyresearchjourn...he-root-of-persistent-antigens-and-long-covid

𝐏𝐫𝐞𝐩𝐫𝐢𝐧𝐭 𝐢𝐧 𝐦𝐞𝐝𝐑𝐱𝐢𝐯 𝐨𝐧 𝐇𝐋𝐀 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐦𝐚𝐫𝐤𝐞𝐫𝐬 𝐢𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐟𝐨𝐮𝐧𝐝:
Association of Long COVID with HLA-DRB1, HLA-DQA1 and HLA-DQB1 alleles.
Genetic correlation between Long COVID, chronic fatigue syndrome, fibromyalgia and depression.
https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1

𝐓𝐡𝐞 𝐩𝐫𝐞𝐩𝐫𝐢𝐧𝐭 𝐨𝐧 𝐯𝐢𝐫𝐚𝐥 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐬𝐩𝐮𝐭𝐮𝐦 𝐨𝐟 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐌𝐄/𝐂𝐅𝐒 𝐫𝐞𝐯𝐞𝐚𝐥𝐞𝐝:
ME/CFS patients, compared to controls, have a significantly higher EBV load.
https://www.preprints.org/manuscript/202502.0185/v1

𝐓𝐡𝐞 𝐬𝐭𝐮𝐝𝐲 𝐢𝐧 𝐅𝐫𝐨𝐧𝐭𝐢𝐞𝐫𝐬 𝐢𝐧 𝐂𝐞𝐥𝐥𝐮𝐥𝐚𝐫 𝐚𝐧𝐝 𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐌𝐢𝐜𝐫𝐨𝐛𝐢𝐨𝐥𝐨𝐠𝐲 𝐬𝐡𝐨𝐰𝐞𝐝:
Hypothalamic-pituitary-adrenal (HPA) axis dysfunction and its impact on immune regulation.
https://www.frontiersin.org/journal...logy/articles/10.3389/fcimb.2024.1501949/full

𝐓𝐡𝐞 𝐬𝐭𝐮𝐝𝐲 𝐢𝐧 𝐒𝐩𝐫𝐢𝐧𝐠𝐞𝐫 𝐍𝐚𝐭𝐮𝐫𝐞 𝐨𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐇𝐏𝐀 𝐚𝐱𝐢𝐬 𝐟𝐨𝐮𝐧𝐝:
Evidence of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with COVID-19 and Long COVID. Hypopituitarism in some patients after SARS-CoV-2 infection.
Possible relationship between virus-induced chronic inflammation and alterations in cortisol production.
Impact on immune regulation due to persistent hormonal deficiencies.
Pituitary defects may persist long after initial infection, possibly contributing to “prolonged COVID syndrome.”
https://link.springer.com/article/10.1007/s11102-024-01463-3

𝐏𝐫𝐞𝐩𝐫𝐢𝐧𝐭 𝐢𝐧 𝐦𝐞𝐝𝐑𝐱𝐢𝐯 𝐨𝐧 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐢𝐭𝐬 𝐫𝐞𝐥𝐚𝐭𝐢𝐨𝐧𝐬𝐡𝐢𝐩 𝐭𝐨 𝐯𝐢𝐫𝐚𝐥 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 𝐟𝐨𝐮𝐧𝐝:
Matunine hypocortisolism similar to those observed in patients with Long COVID.
Relationship between ME/CFS and neuroimmune axis dysfunction.
https://www.medrxiv.org/content/10.1101/2024.09.26.24314417v2

𝐀𝐥𝐥 𝐭𝐡𝐞𝐬𝐞 𝐬𝐭𝐮𝐝𝐢𝐞𝐬 𝐫𝐞𝐢𝐧𝐟𝐨𝐫𝐜𝐞 𝐭𝐡𝐞 𝐢𝐝𝐞𝐚 𝐭𝐡𝐚𝐭 𝐭𝐡𝐞𝐬𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐬𝐡𝐚𝐫𝐞 𝐚 𝐜𝐨𝐦𝐦𝐨𝐧 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦, 𝐚𝐬 𝐝𝐞𝐬𝐜𝐫𝐢𝐛𝐞𝐝 𝐢𝐧 𝐨𝐮𝐫 𝐦𝐨𝐝𝐞𝐥.

𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧: 𝐭𝐡𝐢𝐬 𝐢𝐬 𝐧𝐨𝐭 𝐚 𝐩𝐫𝐨𝐛𝐥𝐞𝐦 𝐮𝐧𝐢𝐪𝐮𝐞 𝐭𝐨 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬, 𝐢𝐭 𝐢𝐬 𝐚𝐧 𝐢𝐦𝐦𝐮𝐧𝐞 𝐬𝐲𝐬𝐭𝐞𝐦 𝐩𝐫𝐨𝐛𝐥𝐞𝐦.

𝐓𝐡𝐢𝐬 𝐢𝐬 𝐧𝐨𝐭 𝐚𝐛𝐨𝐮𝐭 𝐛𝐞𝐢𝐧𝐠 𝐟𝐨𝐫 𝐨𝐫 𝐚𝐠𝐚𝐢𝐧𝐬𝐭 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬. It's about understanding that some people have a genetic predisposition that makes them more vulnerable to developing post-viral and post-vaccine diseases.

𝐓𝐡𝐞 𝐫𝐞𝐚𝐥 𝐩𝐫𝐨𝐛𝐥𝐞𝐦 𝐢𝐬 𝐭𝐡𝐚𝐭 𝐭𝐡𝐞𝐫𝐞 𝐢𝐬 𝐬𝐭𝐢𝐥𝐥 𝐧𝐨 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐬𝐜𝐫𝐞𝐞𝐧𝐢𝐧𝐠 𝐭𝐨 𝐢𝐝𝐞𝐧𝐭𝐢𝐟𝐲 𝐰𝐡𝐨 𝐡𝐚𝐬 𝐭𝐡𝐞𝐬𝐞 𝐚𝐭-𝐫𝐢𝐬𝐤 𝐇𝐋𝐀-𝐈𝐈 𝐚𝐥𝐥𝐞𝐥𝐞𝐬 𝐛𝐞𝐟𝐨𝐫𝐞 𝐜𝐞𝐫𝐭𝐚𝐢𝐧 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐚𝐫𝐞 𝐠𝐢𝐯𝐞𝐧 𝐨𝐫 𝐛𝐞𝐟𝐨𝐫𝐞 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧.

The debate should not be “vaccine yes or no”, 𝐛𝐮𝐭 𝐡𝐨𝐰 𝐝𝐨 𝐰𝐞 𝐦𝐨𝐯𝐞 𝐭𝐨𝐰𝐚𝐫𝐝𝐬 𝐩𝐞𝐫𝐬𝐨𝐧𝐚𝐥𝐢𝐳𝐞𝐝 𝐦𝐞𝐝𝐢𝐜𝐢𝐧𝐞 𝐭𝐡𝐚𝐭 𝐩𝐫𝐞𝐯𝐞𝐧𝐭𝐬 𝐭𝐡𝐞𝐬𝐞 𝐚𝐝𝐯𝐞𝐫𝐬𝐞 𝐫𝐞𝐚𝐜𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐬𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐚𝐥𝐬.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐭𝐨 𝐤𝐞𝐞𝐩 𝐭𝐡𝐞 𝐝𝐢𝐬𝐜𝐮𝐬𝐬𝐢𝐨𝐧 𝐬𝐜𝐢𝐞𝐧𝐭𝐢𝐟𝐢𝐜, 𝐧𝐨𝐭 𝐢𝐝𝐞𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥.

More information in this post: https://x.com/manruipa/status/1893679885559759258