Dr. Bruno Paiva and Mr. Manuel Ruiz-Pablos, Hypocortisolemic ASIA: a vaccine- and chronic infection–induced syndrome behind the origin of Long Covid and myalgic encephalomyelitis (Frontiers in Immunology
“The Solve Ramsay Research Grant has been fundamental for our work, as it has provided us with the necessary resources to be able to start the line of research on the possible presence of an acquired immunodeficiency in patients with ME/CFS and Long Covid. The Ramsay grant has allowed us to conduct several review studies and a study in patients with ME/CFS and Long Covid to identify the possible existence of genetic and immunological markers that could demonstrate possible immunodeficiency. These results will be published in the coming months. Without the Ramsay grant, we would not have been able to perform these analyses in patients due to budgetary constraints.”
Dr. Paiva and Mr. Ruiz-Pablos believe ME/CFS, Long Covid, and post-vaccine COVID-19 syndrome are related to (if not examples of) autoimmune/inflammatory syndrome induced by adjuvants (ASIA), a syndrome for which vaccine adjuvants cause symptoms. According to the authors’ model, some patients are genetically dispositioned to have improper immune responses not only to vaccine adjuvants, but also to viruses like EBV or SARS-CoV-2. These improper responses bring about disease. For example, the patients’ T cells may go haywire and attack the body’s own cells and tissues. And patients’ B cells may produce too many antibodies or antibodies that target the body’s molecules (autoantibodies). Most relevant for Paiva and Ruiz-Pablos’s model—this improper immune response may severely damage the pituitary gland. Many patients with ME/CFS have autoantibodies against pituitary tissue. EBV, SARS-CoV-2, and other relevant viruses can infect pituitary cells as well, further damaging the gland.
How could a damaged pituitary gland cause ME/CFS or Long Covid? A damaged pituitary gland produces less adrenocorticotropic hormone, which leads to less cortisol. Cortisol is critical for providing energy to deal with physical or emotional stress and for controlling inflammation and immune responses. With a damaged pituitary gland, a patient may experience hypocortisolism (insufficient cortisol). (In fact, patients with ME/CFS or Long Covid often have chronically low cortisol levels. And patients with especially severe ME/CFS or COVID-19 can have autoantibodies against adrenocorticotropic hormone, further inhibiting cortisol.) In a hypocortisolemic state, a patient may have insufficient energy to deal with physical and emotional stress. After exercising, the patient may become exceptionally tired, dizzy, or disoriented or may experience general malaise; these are hallmark symptoms of ME/CFS and Long Covid. The hyperactive immune system; the chronic viral infection; the hypocortisolism—these may eventually exhaust the immune system, leading to chronic disease or post-vaccine syndrome.
“We have identified a possible pattern of altered immune response in patients with Long Covid [or] ME/CFS [or] induced by vaccines or chronic infections, which could be associated with autoimmune hypocortisolism. The grant allowed us to find possible links between Long Covid, ME/CFS, and post-vaccinal syndromes,” said Mr. Ruiz-Pablos.
This new model also suggests we might prevent ME/CFS and Long Covid by treating patients with corticosteroids to replenish cortisol levels. Also useful would be ginseng and vitamin C (to help make more cortisol and to relieve oxidative stress and inflammation); DHEA (because corticosteroids adversely affect DHEA levels); antivirals; and glutathione-producing supplements (like n-acetylcysteine, alpha-lipoic acid, S-adenosylmethionine, selenium, and B-complex vitamins). This therapeutic cocktail might help normalize cortisol levels and immune responses, boost pituitary functions, reduce inflammation and oxidative stress, and eradicate the virus before the disease takes hold. On the other hand, this model suggests we should not use immune checkpoint inhibitors to boost immune responses. Immune checkpoint inhibitors might worsen autoimmune responses, further damage pituitary tissues, and further exhaust immune systems.
The Spanish team noted that they will next use their model to develop better ways to diagnose and treat patients. Mr. Ruiz-Pablos added, “Our goal is to better understand how this hypocortisolemic syndrome impacts long-term health and how we can identify key biomarkers to improve diagnosis and treatment. The next step is to validate these potential biomarkers in large cohorts of patients and explore whether the therapies proposed in our latest published paper could improve the quality of life of these patients.”
Dr. Paiva and Mr. Ruiz-Pablos are especially grateful to donors and patients for their support. They told us, “We would like to express our sincere thanks to all donors and patients who support Solve and their Ramsay Research Grant program. Your generosity and commitment make research into these diseases possible and allow us to advance our understanding and treatment of Long Covid, ME/CFS, and post-vaccinal syndromes. We are deeply grateful for your continued support, which is critical to improving the quality of life for so many people affected by these debilitating conditions.”