Long COVID and Immune Dysfunction with Dr. Aristo Vojdani: Rational Wellness Podcast 294

Dr. Aristo Vojdani discusses Long COVID and Immune Dysfunction at the Functional Medicine Discussion Group meeting on January 26, 2023 with moderator Dr. Ben Weitz.

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Podcast Highlights

7:14  Between 1990 and 2000 those practicing medicine were facing a new disease that was called chronic fatigue/fibromyalgia.  These patients were fatigued and had trouble getting out of bed for a period of more than six months.  A number of organs were affected, including the gastrointestinal, pulmonary, muscular, skeletal, brain, and the immune systems.  Many articles were published in scientific journals and some felt that Epstein Barr virus was responsible for chronic fatigue/fibromyalgia, while others felt that cytomegalovirus or HSV1 and 2, or HHV-6, HHV-7, HTLV-1, Spumavirus, chlamydia, or mycoplasma infection were responsible.  These were also very similar to the symptoms displayed by patients with a history of exposure to toxic chemicals, molds, mycotoxins, or silicon breast implant.  It became clear that the cause of chronic fatigue/fibromyalgia was multifactorial. In 1999 in the Journal of Internal Medicine, Dr. Vojdani published a letter that a Single aetological agent may not be feasible in chronic fatigue syndrome.  Not much has changed since 1999 with chronic fatigue/fibromylagia, except that the name was changed to myalgic encephalomyelitis/chronic fatigue syndrome and now the SARS-CoV-2 virus may be playing a role as this condition appears to be part of long COVID. 

13:40  10-20% of individuals who had COVID may develop long COVID.  The majority of cases are those that had severe COVID, though not necessarily.  COVID may lead to the reactivation of EBV, HHV-6 and other viruses and this may contribute to the development of long COVID.  These reactivated viruses may produce super antigens in order to hide from the immune system and this may cause a disturbance in the gut microbiota.  By running the Lymphocyte Map test, clinicians can design treatment modalities.

16:12  Dr. Vojdani has published nine articles on COVID in the last few years, including two articles published in Frontiers in Immunology in 2021 and in Clinical Immunology in 2020 reporting their research that 20-25 human tissue antigens strongly reacted with monoclonal antibodies made against the SARS-CoV-2 virus, which is the best evidence of cross reactivity between SARS-CoV-2 and human tissue. This shows the extreme level of potential autoimmunity of the SARS-CoV-2 virus. [Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases, A. Vojdani, E. Vojdani, D. Kharrazian.]  Therefore, autoimmunity is definitely a component of long COVID.  

20:02  What is Long COVID?  According to the CDC, Long COVID is defined as a range of new or ongoing health problems that people can experience four or more weeks following the initial SARS-CoV-2 infection:  1. Shortness of breath, 2. Memory loss, 3. Fatigue, 4. Anosmia (loss of sense of smell), 5. Gastrointestinal distress, 6. Autoimmune symptoms, 7. other symptoms.  There are five major hypotheses: 1. Viral persistence, including in the GI tract and the brain that is not detected by blood tests, 2. Reactivation of latent viruses such as EBV and HHV-6, 3. The expression of viral superantigens in order to hide from the immune system, 4. Disturbance of the gut microbiome, and 5. Multiple tissue damage, immune disorder and autoimmunity. 

23:30   Viral Persistence.  Why does viral RNA persist after recovery from infection?  While we don’t know, there are a number of host factors that affect the immune function of the person.  The immune system should be strong enough to get rid of COVID a week or two later, but if there is an immune disorder or malnutrition, or a lack of exercise, the immune system may be too weak to clear the virus.

27:30  Reactivation of latent viruses, such as EBV, HHV-6, and CMV.  EBV and HHV-6 tend to infect most of us around age 2-4 and some children also develop infectious mononucleosis. EBV tends to become dormant in cells, esp. the B cells and if we suffer some kind of stress, or malnutrition or another viral infection and EBV can become reactivated and thus EBV can play a role in long COVID symptoms.  By age 3, 90% of Americans are infected by HHV-6 via the nasal cavity.  This virus persists in various tissues, including in glial cells. This virus may play a role in a number of autoimmune diseases, including multiple sclerosis, Alzheimer’s, Parkinson’s, myalgic encephalomyelitis, lupus, collagen vascular disease, encephalitis, epilepsy, thyroid autoimmunity, and Guillain-Barre syndrome. Here is the latest paper that Dr. Vojdani has published on COVID: Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

39:14  Expression of Superantigens.  Superantigens are produced by pathogenic viruses as a defense mechanism against the immune system. These superantigens look like human superantigens like human heat shock protein and therefore the immune system may not go after the virus, allowing the virus to divide and spread.  Superantigens cause excessive activation of the immune system and massive cytokine release, which may lead to autoimmunity multiple organ failures and may even may cause death. That’s why it’s so important to look at Lymphocyte Map test from Cytokine Labs. 



Dr. Aristo Vojdani is the Father of Functional Immunology and he has dedicated his life’s research to helping us figure out what are the triggers for autoimmune diseases and many of the tests he has developed for Cyrex Labs are focused on this.  Dr. Vojdani has a PhD in microbiology and immunology and he has authored over 200 scientific papers published in peer reviewed journals. Dr. Vojdani is the co-owner of Immunosciences Lab in Los Angeles, which offers testing for various types of infections, including Lyme Disease. He is the Chief Science advisor for Cyrex Labs, whom he has developed all of the testing for, including the Lymphocyte Map test, Array 2 for Leaky Gut, and Array 5, The Multiple Autoimmune Reactivity Panel, and from Immunosciences, the Autoimmune Viral Trio Panel

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast. Tonight we’re very happy to be joined by one of our favorite speakers, esteemed integrative immunologist, Dr. Aristo Vojdani, who will be telling us how to identify immune system imbalances related to long COVID. And you’ll have some ideas for what we can do about this. I’m Dr. Ben Weitz. I’m going to make some introductory remarks and then I’ll introduce our two sponsors, Integrative Therapeutics and Cyrex Labs, and then I’ll introduce our speaker for this evening.  I encourage each of you to participate and ask questions by typing in your question in the chat box, and I’ll either call on you or simply ask Dr. Vojdani your question when it’s appropriate. Dr. Vojdani usually likes to wait until the end for the questions, but I’m happy to stay as long as we have questions, so there’s no time limit, but Dr. Vojdani will probably talk for about 45 minutes or so and then we’ll do Q and A afterwards. So now I’d like to introduce Steve Snyder from Integrative Therapeutics, one of our sponsors for this evening to tell us some information about some of their products. Steve.

Steve:                                   Hi there. We actually have quite a few that are highly requested for the post COVID long hauler stuff. Rather than just blather on about them, I’m going to put them into the chat, so if anybody has any questions on them or wants to try something, you can reach out to me that way and we can get you taken care of. But thank you. I’m looking forward to hearing Dr. Vojdani’s talk. Thank you.

Dr. Weitz:                            Okay. Thank you, Steve. And now we have Heather Sunshine from Cyrex Labs and she’s going to take a few minutes to tell us about some of the Cyrex Labs.

Heather:                              Thank you, Dr. Weitz. Hello everyone. My name is Heather Sunshine, territory manager at Cyrex Lab. Cyrex is a functional immunology lab and our focus is autoimmunity. We have environmental panel since we understand the environment plays a huge role and is a contributor to autoimmunity. The role of foods and the extrinsic causes such as infections, toxins and environmental antigens are critical triggers of immune dysfunction. So we offer barrier testing. We understand a leaky gut can lead to a leaky immune system and a leaky brain. We also have an Alzheimer’s links panel, and I can’t stress enough early detection of environmental factors that contribute to the pathogenesis of Alzheimer’s disease is the most crucial for developing interventional programs that will slow down or stop the progression of the disease. But what I’m excited to share with you today is the lymphocyte map. The lymphocyte map measures the integrity of the immune system at the cellular level.

                                                We are using advanced flow cytometry method that combines laser technology with monoclonal antibodies to measure the properties of living cells based on size, shape, density and granularity. Therefore, providing high precision count of various lymphocytes subpopulations. It identifies the patterns of balance or imbalance of T-cells, B-cells, and natural killer cells detected in the blood. Learn more about our testing or to sign up for an account, you can visit us at visit@jointcyrex.com or you can email me at heather.s@cyrexlabs.com. Thank you Dr. Weitz, I mean for providing us such a educational and informative forum. I’ve always enjoyed you interviewing top clinicians and educators to help us navigate our health journey, and I’m excited to listen to our chief scientist advisor, Dr. Aristo Vojdani, speak tonight. Thank you.

Dr. Weitz:                            Thank you, Heather. So our speaker for tonight, Dr. Aristo Vojdani. He’s the father of functional immunology and he’s dedicated his life to helping us to figure out what are the triggers for autoimmune diseases. And many of the tests he has developed for Cyrex Labs are focused on this, including his newest test that Heather mentioned, the lymphocyte map. Dr. Vojdani has a PhD in microbiology and immunology. He’s authored over 200 scientific papers, probably 300 by now, published in peer review journals. He’s just informed me he’s published over nine papers just in the last year or so about COVID-19, which is a topic for tonight.  So we’re going to be talking about long COVID, and what are some of the factors, mechanisms for long COVID, how can we test for it, what can we do about it?   And Dr. Vojdani is the chief science advisor for Cyrex Labs who he’s developed all the testing for.  He also is a co-owner of Immuno Sciences Lab in Los Angeles, which offers testing for various types of infections, including his latest test, the Autoimmune Trio Test, that test for antibodies to COVID, Epstein Barr and HHV-6, which Dr. Vojdani will mention tonight. He’s also a professor in the Department of Preventive Medicine in Loma Linda University. Dr. Aristo Vojdani, my friend Ari, thank you so much for joining us tonight and honoring us with your presence.

Dr. Vojdani:                        Thank you so much Dr. Weitz, and thank you for all the participants. I was very happy to see some very, very familiar faces. So about few minutes ago I asked Dr. Weitz, where were you in 1990? And his answer was that at that time, almost two years into finishing my school and I started my clinic. So it’s interesting.  At the same time also, 1989, I started Immunosciences Lab while also I was associate professor at the Charles Drew UCLA School of Medicine.  The reason I brought this issue of 1990, because between 1990, all the way to year of 2000, those who were practicing medicine were facing or facing new disease in subgroup of their patients.  And then they call that chronic fatigue fibromyalgia.  These individuals, they could not get out of bed. They lost their daily activity more than 50% and again, they could not get out of bed more for more than period of six months.  In these individuals, different organs were on fire including gastrointestinal, pulmonary, muscular, skeletal, brain, and of course the immune system or the immune function. That’s why at even another name that was given to this disease was called chronic fatigue and immune dysfunction syndrome. CFIDS.  Then between these years, many, many articles published in different scientific journals, each one of them talking about different factors, some that were talking about, Epstein Barr virus is responsible for chronic fatigue/fibromyalgia. The other were saying no, it is cytomegalovirus. Some that were saying no, it is HSV1 and 2. And some were publishing about HHV-6, HHV-7, HTLV-1, Spumavirus, chlamydia, mycoplasma, and many, many more. In fact, in 1998 and 1999, I published several articles who looked at different patients with chronic fatigue fibromyalgia and found that mycoplasma ferment by PCR then by PCR was elevated in these patients.  Furthermore, we found almost similar symptoms in patients who had history of exposure to toxic chemicals, molds, mycotoxins, silicon breast implant. So everybody was talking about different factors and that’s why in 1999 in Journal of Internal Medicine, as you can see in here based on the several articles that I wrote, scientists from Italy wrote a letter to Journal of Internal Medicine saying that chronic fatigue is almost like Addison’s disease.  And so I had to answer him, and this is the letter that I wrote in 1999, so please bear with me and look at the title.  Single ideological agent may not be feasible in chronic fatigue syndrome.  And I’m not going to read the rest whatever is written in here, but if you’d like to have a copy of this letter, I’ll be very happy to share with you because in here I am saying that chronic fatigue fibromyalgia is multifactorial and therefore it is waste of time to look for a single factor being responsible for its induction and also it is in a waste of time to look for a single medication or remedy for its treatment.  [Here is Dr. Vojdani’s letter: Single aetological agent may not be feasible in chronic fatigue syndrome. Some people, they got really mad at me that a scientist, by saying that a scientist should not be this pessimistic, but I was realistic, I wasn’t pessimistic. So since then, really not much has been changed. We know that chronic fatigue fibromyalgia, which they changed the name to ME/CFS or myalgic encephalomyelitis chronic fatigue syndrome. So still it is multifactorial disorder. And now we see similar or significant overlap between chronic fatigue fibromyalgia with long COVID with only difference is that we know for sure in the case of long COVID, SARS CoV-2 is one out of many factors that playing a role. So let’s go ahead and discussing this issue associated with long COVID.

So based on statistic, 10 to 20% of individuals who had COVID may develop long COVID. Majority of cases are in individual with severe COVID, but not necessarily. Some of them could be, could have even mild COVID and may develop also long COVID.  So I’m going to talk about that. In addition to SARS-CoV-2, Epstein Barr virus, HHV-6 and other viruses may contribute to development of long COVID. Then due to these reactivated viruses, the viruses produce super antigens in order to hide from the immune system, but that the production of super antigens by the viruses causing reactivation of the immune system causing disturbance in gut microbiota. And this altogether could result in hyper inflammation and poly autoimmunity meaning many autoimmune diseases. By the way, I’m going to touch about the importance of laboratory testing including antibodies against SARS-CoV-2, EBV, HHV-6, and also we have to look at gut permeability and autoimmunity. And finally, the importance of lymphocyte map, as it was mentioned by Heather from Cyrex, is becoming very, very important in patient with long COVID. Why? Because based on lymphocyte map and based on their immune print, clinicians can design treatment modalities. So we’ll discuss all of that during the next probably 40 minutes. So let’s go ahead.

                                                Dr. Weitz was kind enough to mention that I did publish nine different articles, including the last one is coming up just this week in the journal called Viruses. But one of the most important article that I published in Frontiers in Immunology in January, 2021 and another one in December or October, 2020, published in Clinical Immunology. In these two, in this research project, we took monoclonal antibodies made against SARS-CoV-2, spike protein and nuclear protein and reacted that with about 60 different human tissue antigens.  And we found about 20 to 25 of those tissue antigens reacted strongly with SARS-CoV-2 monoclonal antibodies.  That is the best evidence of cross reactivity between SARS-CoV-2 and human tissue.  And here you see in this picture the major, major tissues which antibody made against SARS-CoV-2 reacted with.  So let’s right here, tight junctions, leaky gut, skin disorder, nervous system, many tissues, three or four of these 20 something tissue antigens were originated from the nervous system from the brain, thyroid autoimmunity, joint muscle, liver, cellular components such as ANA, ENA, mitochondria, smooth muscle, the muscle we have there.  And also finally, some of the antigens produced by neutrophil such as neutrophil cytoplasmic antigens. And this article so far downloaded by more than 200,000 individuals and most of the articles that I wrote in such a period of two or three years, the most that downloaded or read by different individuals was 3000, 5,000, 10,000. But this one is among the upper 99% of all the articles published in Frontiers in Immunology. So I’m very proud of that. So that’s about the autoimmunity. So now, because the reason I brought that up because autoimmunity you’ll see is a major components of long COVID or individual with long COVID may end up with autoimmune disease.  In fact, those patients which we met during 1990 through 2000, who did suffer from chronic fatigue fibromyalgia, and we tested them for antibodies, we tested them for cell mediated immunity. Unfortunately five years later, 10 years later, majority of them ended up with different autoimmune diseases. So we should not be surprised that autoimmunity is going to be a major components of long COVID.

So what is long COVID? So this is according to CDC, it is defined as a range of new returning or ongoing health problems that people can experience four or more weeks following the initial SARS-CoV-2 infections. And some of their symptoms includes shortness of breath, memory loss, fatigue, anosmia, GI distress, autoimmunity, and believe me, additional 90 different symptoms that I could not mention them in here, but these are the major symptoms.  But for matter of simplicity, I am going to talk about five major hypothesis about long COVID. You may ask why am I calling these hypothesis? Because really right now lots of research is ongoing. We cannot say everything is definite in relation to long COVID. That’s why we have to do more research. So these five major hypothesis, one of them is viral persistence in various tissues including GI, especially gastrointestinal, brain, those tissues that there are receptors for SARS COVID 2. Number two, reactivation of latent viruses such as EBV and HHV-6. I mentioned earlier that the viruses in order to hide from the immune system, they express super antigens. So that’s number three. You have to deal with that. All these together can disturb the gut microbiome. So therefore disturbance of gut microbiome is major component of long COVID and at least, I read at least about 50 different articles published in different scientific journals about the role of gut microbiome in long COVID.  And finally all of that may result in multiple tissue damage, immune disorder and autoimmunity. So we have to talk about all of this. So long COVID. So we mentioned about some of these factors, but we should not forget that the host factors such as obesity, type two diabetes, hyperactivation of the immune system and many other host factors, the exposome factors in general, what we are exposed on daily basis to play a significant role in development of long COVID.

So what is viral persistence? Instead of reading all of that, let me just in one sentence saying that most of us are lucky that when we get COVID five days later, one week later, two weeks later, the virus is gone, the immune system is strong enough to take up the viruses and get rid of them through the macrophages, dendritic cells and cytotoxic lymphocytes and natural killer cells.  So the body overcomes these viruses, but unfortunately in certain individuals due to immune disorder, due to malnutrition, due to lack of exercise, all of that together, which we call that lifestyle medicine, lifestyle in general, may not be able to clear the virus.  And the virus or its particles may stay in the tissue and then later on they may contribute this viral particles become full viruses and they divide and cause significant problem in these patients which may result in long COVID. So this is one of the drawings that we show that ACE two receptor, the SARS-CoV-2 bind into that injects its RNA into the nucleus, the viral nucleic acid RNA replicates itself and then becoming the RNA, becoming the virus and the virus get out of that and divides and finally spread and infect additional epithelial cells, whether they’re in the lungs or in the gut or somewhere else in the body. So infection, replication and spread.  So the question is why does viral RNA sometimes persist after recovery from acute infection? Again, we don’t have really the answer for that. I just touched upon that all depends on the host factors and the immune system and immune function of individual. So some are very lucky they can get rid of the virus and it’s RNA, but the others unfortunately cannot.

So to find out whether or not an individual is suffering from viral persistent, I recommend to do SARS-CoV-2 IgG against spike and nuclear protein. And if it’s significantly elevated, could be in relation to the virus which stayed in the tissue. But also you may ask me, I had four or five and six vaccinations maybe due to that, that I have high levels of spike and nuclear protein and that is definitely possible.  That was just couple of slides about viral persistent.

Now reactivation of latent viruses in long COVID, and I’m going to read this because it’s important. So studies have associated reactivation of viruses such as EBV, HHV-6, CMV with the severity and the length of COVID-19 symptoms viruses and their parts may under certain conditions survive the defensive response of the immune system and hide in tissue reservoir. These latent viruses may then be activated, and this reactivation facilitates the entry of the SARS-CoV-2 into the cells enhancing viral load and severity of the symptoms. So number one is Epstein Barr virus. Remember that I mentioned this virus also, its association with chronic fatigue fibromyalgia. So Epstein virus or herpes type four infects most of us around age two, three, and four.

                                                And some children also develop mono infectious mononucleosis. And these individuals produce high levels of IGM against VCA and EBNA. So however, following the acute phase, this virus loves the B cells and some other cells and become dormant in our cells, especially B cells. As long as our immune system is strong, they do not become reactivated. As soon as we suffer from some kind of stress, malnutrition, other factors, they become reactivated and contribute significantly to different disorders including long COVID. But also Epstein Barr virus, it’s known as one of the major viruses causing or involved in autoimmune diseases. And here I have about eight or nine or 10 of out of 30 different autoimmune diseases associated with Epstein Barr virus, so inflammatory bowel disease, lupus, rheumatoid arthritis, Churg-Strauss syndrome, MS especially, type one diabetes, polyneuropathy, thyroid autoimmunity, celiac disease and autoimmune liver disease or major autoimmune diseases associated with Epstein Barr virus.

                                                So as you can see this article from pathogens journal called pathogens, they’re investigating the role of Epstein Barr virus reactivation in long COVID. And in fact you see in blue this Epstein Barr virus could be involved in prevalence of long COVID symptoms. 30% of the symptoms, or in this case 30% of those who have long COVID may be associated with Epstein Barr virus. And when they measured antibodies against EBV EA-D or early antigen and EBV VCA IgM, as you can see in blue they say we found that 66.7% of long COVID subjects versus 10% of control subjects in our primary study group were positive for EBV reactivation based on what I mentioned. So EBV seems played a significant role in long COVID.  And look at this conclusion, these findings suggest that many long COVID symptoms may not be a direct result of SARS-CoV-2 virus, but maybe the results of COVID inflammation induced by EBV reactivation. Very well said. Okay, so EVB.

Next, human herpes type 6 also was among the viruses, which was evolved in chronic fatigue fibromyalgia also we are getting that around age three. And this virus labs many cells including glial cells and that’s why many patient with multiple sclerosis are having problem with herpes, human herpes type 6, very similar to Epstein Barr virus. This virus also is involved in many autoimmune diseases including Alzheimer’s, Parkinson’s, you see myalgic, encephalomyelitis, lupus, Churg-Strauss syndrome, collagen vascular disease, encephalitis, epilepsy, thyroid autoimmunity, Guillain-Barre syndrome and of course I mentioned multiple sclerosis.   So here some articles supporting that measurements of antibodies against EBV HHV-6 to some degree also cytomegalovirus. So health risk virus infections and post COVID manifestations a pilot observational study. So they showed that EBV reactivation in about 43%, HHV-6 in 25%, which is very significant and combination of EBV and HHV-6 in 32.4%. So looking at EBV and HHV-6 is extremely important and measure IgG and IgM antibody against that in patients with long COVID is becoming very, very important. Okay. So therefore patients with post COVID syndrome and re reactivation of EBV and HHV-6 infections are at high risk of developing various pathologies including rheumatic rheumatologic diseases because we know these two viruses are involved in autoimmune diseases and therefore we should not be surprised why patients with long COVID may develop or will develop autoimmune diseases including rheumatologic diseases.

                                                Now some mechanistic explanation. Epstein Barr virus lytic replication induces ACE two expression and enhances SARS-CoV-2 entry into epithelial cells. So let me show you the pictures. So think about hand and the glove. Okay. So the glove is SARS-CoV-2 and the hand is… No, the hand is SARS-CoV-2 and the receptor is the glove. So by itself SARS-CoV-2 virus that attempts to match, but you see that only three fingers match, but the two others do not match. So this is partial match between SARS-CoV-2 and ACE two receptor. So I hope you are with me so far. Now in addition to SARS-CoV-2, EBV infects the epithelial cells. Now after five fingers, the gloves can fit with four but not with the fifth one. When HHV-6 comes along, you see now there is a perfect match between hand and the glove and therefore EBV and HHV-6 contribute significantly to spread of SARS-CoV-2 into the tissue. And together SARS-CoV-2, EBV and HHV-6 may contribute to long COVID and associated inflammatory and autoimmune disorders.

                                                So that’s for simplicity of mechanistic or mechanism of action. So at immunoscience lab we have this panel we call it Viral Panel Premier, where we look at EBV, CMV, HSV-1, HSV-6, Varicella-Zoster in some individuals also small percentage VCV contributes to long COVID. As you know, also, some individuals who had vaccines had or did suffer from recurrent of shingles, which is induced by Varicella-Zoster. So therefore we will come in this panel to detect the viruses. However, in order to save money, we put together these three viruses, which we call them autoimmune viral trio panel, SARS-CoV-2, EBV and HHV-6 as part of detection of long COVID. But you’ll see additional tests later on as well.

                                                Now let’s move on from pre reactivation of latent viruses to super antigens. What are super antigens? Antigens that are produced by some pathogenic viruses as a defense mechanism against the immune system. They express these super antigens which look like human super antigens, like human heat shock protein 60, 70, 90. So when the body looks or the immune system looks at the virus because they express something similar to human tissue, they may not go after the virus and the virus can divide and spread in our tissue. However, these super antigens may cause non-specific activation of T-cells. They induce polyclonal activation of T-cells, massive cytokine release that you have seen in patient with COVID resulting in excessive activation of the immune system, which may lead to autoimmunity multiple organ failures and unfortunately in some even may cause death. That’s why it’s so important to look at lymphocyte map that discussed by Heather on behalf of Cyrex Laboratories.

                                                So here some articles for example, you see in medical hypothesis about persistent SARS-CoV-2 infections that may contribute to long COVID. The virus super antigens could overstimulate antivirus immune responses and thereby induce negative feedback loops that paradoxically allow the virus to persist. I think earlier I explained that. So here in the same article medical hypothesis, they showed dendritic cells. Okay. Dendritic cells right here. And they take the antigen presented on major histocompatibility to T-cells and then the immune system react against that when we produce some antibodies and we call that balanced immune system, but when in addition, when super antigens right here on the right, when super antigens are presented by dendritic cells to T lymphocytes, they’re activating large subgroup of non specific and then they divide, they become over activated. And this over activated of immune cells can release many pro-inflammatory cytokines can cause damage and damage to our tissue may result in autoimmunity.

                                                So we started with viral persistent activation of latent viruses super antigens. All of these together may contribute to disturbance in gut microbiota in long COVID. And in the next slide you see that some articles about gut microbiota dynamics in a prospective cohort of patients with post COVID syndrome. And I’ll go right away to the next slide, is the good versus bad. Under normal condition we have balance between these two groups of bacteria, but instead of having balance, you see that these groups of bad bacteria are enriched and the good bacteria are depleted. And you see for example, enterococcus intra bacteria. That’s why we measure antibodies against lipopolysaccharides produced by e-coli, salmonella and more, which is part of Array 2 in many patients including long COVID. Also, these pictures may justify the use of prebiotic and probiotics for patients with long COVID. So this is the Array 2 intestinal barrier antigen permeability screen offered by Cyrex.

                                                I sincerely believe that in addition to those viral antibodies I mentioned before, looking at gut barrier dysfunction which is by Cyrex is extremely important to look at. And this should be part of assessment of long COVID. Now, overactivation of the immune system. So we go one step further, all of that together may contribute to overactivation of the immune system. So here I’m trying to explain about the beauty of the immune system. The immune system in people is as diverse as height, beauty, intelligence, and other human features. Our genomes, lifestyles, and exposomes can affect our immuno type. So believe it, depends on our immuno type. For example, I may be Th1 dominant and you are Th17 dominant. When we get exposed to the same virus, I may have one type of reaction and you’ll have different type of reactions and therefore we have to assess our immune system by lymphocyte map in order to help practitioners to design treatment modalities, one for Th1 and another one for Th17 dominance.

                                                So this is about the immune system and that is why so many people get exposed to the same environmental factors and each one of them have different symptomatologies or they exhibit different symptomatologies. So for many, many years in patients with chronic fatigue fibromyalgia, those who were exposed to toxic chemicals, those who were exposed to molds and mycotoxins, those who had silicon breast and implant, we used to do the upper part only. Okay, meaning looking at T-cells, B-cells, CD4, CD8 and the ratio. And yes, many laboratories right now can do that for you, but believe me, I have seen many patients with absolutely normal CD4, CD8 ratio. But when you look at natural killer cells, three kinds, for example, NK/T-cell. NK/T-cell is not is a kind of natural killer cell, which is T-cell, but it regulates the immune system. And I was reading this article yesterday that Epstein Barr virus, for example, can activate NK/T-cell and NK/T-cell release certain factors, can activate Th1 and therefore I may suffer from Th1 dominance.

                                                And that only could be measured by this comprehensive immunophenotyping that’s done only at Cyrex. Many practitioners used to measure cytokines for Th1 or Th2, the same cytokine that you classify that as Th1 for example, interferon gamma could be produced by five different type of cells. So that by itself is not enough. You have to stain directly these cells based on the receptors under surfaces and accurately we can count the number of NK cell, cytotoxic cells, Th1, Th2, regulatory T-cells which keep the balance between different components of the immune system. And finally, T helper 17. This is the kind of panel that I recommend to be part of long COVID or for assessment of immune function and immune system in general. Now many doctors have used the lymphocyte map of Cyrex for many, many patients including for SARS-CoV-2, for long COVID.

                                                And during past year they asked me when we do lymphocyte map, how long we should wait to repeat the test again? My answer always was that six months in some cases, in other cases 12 months. And believe me, if you read this article that was published in Journal Allergy, they’re saying exactly that for mild cases repeated after six months and you see for severe cases repeated after 12 months. So if you do that before, probably you are going to waste your patient’s money. So I’m not here pushing, doing lots of laboratory testing as you can see. So the role of exposome, as I mentioned before, is extremely important in development or becoming Th1 dominant or Th2 dominant or NK/T dominant as you can see in here that if the exposome factor is reactivation of EBV or HHV-6, these two viruses can release super antigen called an enzyme dUTPase.

                                                And that enzyme has significant effect and the cellular components of the immune system can activate the macrophages and dendritic cells, can hyper activate T helper 1, can hyper activate T helper 17, can cause these regulation of regulatory T-cell, can increase NK/T-cell, can activate B-cells to produce too much antibodies. All that together may result in myalgic encephalomyelitis chronic fatigue syndrome and long COVID and overlap between both of them. I think this is a very good slide so far to explain what I mentioned until this point. So the exposomes are actually, the exposome definition is lifetime exposure to external and internal environmental factors. So food additives, preservatives, toxic chemicals, pollutants, bacteria, fungi can change our internal proteins cause oxidation, methylation, citrullination. Also, these exposome factors can change different cells involved in the immune system and the result of that could be inflammation, autoimmunities, allergies, and hyper sensitivities.

                                                That’s why using or ordering lymphocyte map is becoming so important for many patients with exposure to many, many environmental factors including viral reactivation of the immune system and induction of long COVID. So the last part is all that together may contribute to autoimmunity. So you see here that the auto, the wheels or the tires are Th1 one and Th17, okay? And the antibody is the driver. When the immune system is become overactive, the car which is supposed to drive 60 or 70 miles per hour is driving 200 miles per hour. And obviously the results of that will be an accident. And in this case the accident is autoimmunity. So the autoimmunity, there are many stages in autoimmunity.

                                                The green, you see it’s the healthy stage one or silent autoimmunity. You may measure antibodies against thyroid peroxidase, but patient doesn’t have any symptoms. Antibodies are elevated. So we call that the yellow, stage one or silent autoimmunity. But it is at this level that practitioners should detect it, intervene and prevent from stage one to become stage two, which is called autoimmune reactivity, where elevated antibodies with symptoms and loss of function but they are not severe enough to cause destruction of the tissue. If we will not stop autoimmunity at stage two, then it moves to stage three elevated antibodies, significant symptoms and signs and laboratories are abnormal imaging and all that result in significant loss of function, which really you may be able to maintain that patient’s overall health but you are not going to be able to reverse autoimmune diseases.

                                                So couple articles that just let’s review the titles that autoimmunity’s hallmark, post COVID. And believe me, at least more than thousand articles published in the past two, three years about contribution of COVID and post COVID to autoimmunity syndrome. So in the middle you see it’s written latent autoimmunity and poly autoimmunity were found in 83% and 62% are patients respectively. So autoimmunity is major component of long COVID and long COVID from rheumatologic perspective. So now specifically talking about rheumatological disorders and that’s why basic autoimmune panel, particularly anti-nuclear antibody, ENA extractable nuclear antigen, double stranded DNA, rheumatoid factor immune complexes particularly because many labs do not do that. Acting and mitochondrial antibodies, I think the price for this is about, I think altogether, I think it’s covered right there by around $200 something. Many laboratory charged for immune complexes $200. So this should be part of long COVID as well.

                                                And here I would like to share with you a case report of individual with long COVID viral infection and autoimmune reactivity. And this is 28-year-old woman with medical history of previous EBV infection with postviral fatigue. And in 2020 developed myalgia, anosmia and rash. And I’m going to move a little bit faster. And they did some blood testing and they found some abnormalities that I’m going to share with you. So first look at the lymphocyte map. In the lymphocyte map, lymphocytes are significantly elevated, total T-cell is elevated, cytotoxic T-cell is elevated. T helper cells are actually low. But with Th2 dominant, Th1 dominant that that’s very significant. Regulatory T-cells are elevated. They tried to maintain this imbalance. And of course NK/T-cell as I mentioned before, Epstein Barr virus can cause activation of NK/T-cell.

                                                They release certain factors and individuals becomes Th1 dominant. So this is a classical picture of an individual with COVID or long COVID, which based on practitioners try to fix some of these abnormalities. And we did classical autoimmune panel, we found ENA elevated but not 200%. It’s slightly elevated, but that’s significant. That’s why we have to detect the autoimmunity at stage one and not stage two or three. Rheumatoid factor 14, some may say, well that’s only twice higher than reference range. Immune complexes also borderline elevation, but it is significant. Smooth muscle antibody and mitochondrial antibody negative. So we see evidence of autoimmune reactivity in this patient. If we will not treat this patient five years later, that patient will have full-blown autoimmune disease. And then finally we measure SARS-CoV-2 antibody. As you can see significantly elevated, HHV-6, IgG is normal, but look at IgM, very, very elevated among probably 3% to 5% of those who we test on weekly basis have this kind of tighter of antibodies.

                                                And as you can see also there is evidence of EBV reactivation based on IgG against VCA, IGM against VCA, especially early antigen and IgG against nuclear antigen. So there are two items are here. Very significant. IgM against VCA and the early antigen together indicates that reactivation of HHV-6 and EBV and therefore we should not be surprised to see that kind of abnormal panel for autoimmunity. This individual had also abnormal Array 2 meaning Daptomycin is elevated, v is elevated, lipopolysaccharide, both IgG and IgA are highly, highly elevated. So this individual is suffering from leaky gut as well. And also this individual suffering may be from other gastrointestinal disorders including irritable bowel syndrome. And finally this individual had also problem with blood brain barriers. I have seen in 70% of the cases those who have problem with leaky gut also have problem with leaky brain. So all of that we found in this patient and if the doctor who treated this patient will look at the test result based on the test result will treat this individual.

                                                Hopefully after six months or a year we’ll be able to reverse the course of autoimmune disease. So finally in the last three slides I would like to conclude what testing I do recommend for long COVID, MECFS. And these testing are exactly based on the five hypothesis. Viral persistence. We have to measure antibodies against SARS-CoV-2 and nuclear protein. Reactivation of latent viruses. We have to measure IgG and IgM antibodies against EBV and HHV-6 or viral panel premier that is done at immunoscience lab. Completely lymphocyte immunophenotyping because a viral superantigen can activate the immune system and therefore we can detect that by complete lymphocyte immuno phenotyping or lymphocyte map by Cyrex Laboratories. All of that we set can cause disturbance in gut microbiome and intestinal antigen permeability meaning Array 2, which is offered by Cyrex Labs. And finally, multi tissue damage and autoimmunity. We have to look at biomarkers of autoimmunity, autoimmune profile or even Array 5 by Cyrex Laboratories or autoimmune profile by immuno sciences laboratories.

                                                So these are the tests altogether I do recommend for comprehensive evaluation of patients with long COVID, chronic fatigue and fibromyalgia, myalgic encephalomyelitis. Now in relation to treatment, there are many, many articles, but again you see there is no single treatment or modality for disorder which is multifactorial. I’m repeating the same thing that I said in 1998 or 1999. So therefore, based on laboratory testing we have to find, what are the abnormalities? Maybe in one patient is viral persistent, in another one is latent viruses, activation of latent viruses, in another one is disturbance in gut microbiota, in another one’s immune system abnormalities, in another one autoimmunity or combination of all the above. And so therefore you see in some cases we say monoclonal antibodies vaccination, NAD+, hydroxychloroquine, which there are lots of publication. These are all based on articles I read in scientific journals.

                                                Reactivation of latent viruses in a classical antiviral medications, NAD+, vitamin D, strengthening the immune system. And again, the same thing for viral super antigens and disturbance have gut microbiota. You can see some of these change of diet probiotics, prebiotics, acetate, [inaudible 01:05:58], propionate and more. And finally for multiple tissue damage and autoimmunity, identifying which tissue is under attack. Immunosuppressive medication, dexamethasone, vegan diet, highly recommended biologicals that eliminate the B cells that produce antibodies. But believe me, these are not the only suggestions for treatment. There are many more. The other day I was listening to presentation of Dr. Perlmutter, which with Dr. Bland next Tuesday, they’re also going to talk about long COVID and the role of mitochondria and immune dysfunction in long COVID. In one of his slides which I borrowed from him, he mentioned all of these for improved functionality and you can see hyperbaric oxygen therapy, high dose melatonin.

                                                Why? Because I didn’t have time to mention in sub patients with very similar to chronic fatigue fibromyalgia with long COVID, they have problem with hormone such as cortisol, they have low cortisol. I talked about Edison disease that the doctor wrote a letter to the editor. But yes, both of these disorders, patient with this disorders, myalgic encephalitis, chronic fatigue and long COVID, they do suffer from low cortisol and therefore maybe low dose melatonin and some others, and please do not forget here they’re talking about also fasting and exercise. I have two articles, one about fasting, second one is about exercise for prevention of long COVID. And again, don’t forget quercetin, metformin, berberine and many more. So depends on who is the speaker, who is the investigator. Some of them may say use this factor, the other may say use the others. But you have to use combination of all or above because multifactorial disorder could not be cured or managed by a single medicine or single remedy.

                                                So with that I would like to share with you the presentation that I made to you and if you want to read about those five hypothesis in depth, this article hopefully will be published this week. I’ll send a copy two Dr. Weitz and he will share it with you and hopefully you’ll read it and you’ll enjoy it. Thank you so much. This is my ninth article that I’m publishing in scientific journal and this journal is called viruses. Dr. Weitz, thank you so much for inviting me to speak here. It was my pleasure and honor to here.

Dr. Weitz:                            Thank you so much, Ari. Another awesome presentation. I’d like to start by asking a couple of questions. And the first question I have is we’ve heard a lot about one of the negative effects of COVID and also long COVID is cardiovascular micro clotting, a whole series of cardiovascular issues. And you didn’t really mention that.

Dr. Vojdani:                        Well, indirectly, I did mention that in one of the slides that I showed, I showed that monoclonal antibodies react with different tissues including active and striated and smooth muscle. Also, I showed that monoclonal antibodies-

Dr. Weitz:                            So hang on one second.

Dr. Vojdani:                        … fight against nuclear protein cross-reacted with first for lipids or cardiolipin.

Dr. Weitz:                            Okay.

Dr. Vojdani:                        So hundreds of articles published. Yes, I agree with you that due to autoimmunity, to clotting factors and this cross the activity and immune reactivity may end up with some of the disorders that we are familiar with in patients with COVID and long COVID including myocarditis.

Dr. Weitz:                            So is the myocarditis an autoimmune phenomenon or is it just that the virus attacks the heart muscle/.

Dr. Vojdani:                        Myocarditis is an autoimmune disease, but you may say also it has some other components. Yes, but it is classical autoimmune disease that the body attacks the component of the heart cells. And cardiolipin for example, is one of them. And I was listening again to Dr. Perlmutter the other day. He was showing that cardiolipin is the major component of mitochondrial components of the cell.

Dr. Weitz:                            I listened to a presentation by Dr. Mark Houston at the Cassie conference in October and he was talking about a lot of inflammation of the endothelium of the arteries and that being a big factor. And then he had a protocol he recommended to try to treat that.

Dr. Vojdani:                        And also I think Elroy, my son spoke last year at F4N about inflammation and he emphasized all of that autoimmunity against mitochondrial and different components of heart and blood.

Dr. Weitz:                            Somebody asked about, when you talk about high dose melatonin, what dosage are you talking about?

Dr. Vojdani:                        That was the slide I borrowed from Dr. Perlmutter, which on Tuesday at 5:00 PM I think Los Angeles time, he’s going with Dr. Bland and two other speakers are going to talk about long COVID in relation to immunity and mitochondria. So I don’t know the answer, but definitely he knows.

Dr. Weitz:                            Right. Interestingly, the dosage for melatonin for sleep is often very low, three milligrams, something like that. 20 milligrams was the dosage that was popular for more serious conditions like cancer. But recently it’s become popular to use 200 to 300 milligrams of melatonin for things like cancer. So that’s now considered a high dose.

Dr. Vojdani:                        Thank you for the information.

Dr. Weitz:                            Somebody asked, is there any commercially available testing for micro clotting?

Dr. Vojdani:                        No, other than looking at antiphospholipid antibodies or cardiolipin antibodies and alpha beta-2 glycoprotein antibodies, which is related to the platelet antibodies, I think those two are giving some hint about that type of autoimmunity.

Dr. Weitz:                            Anecdotally just I’ve seen in some patients, I’ve seen an elevation of myeloperoxidase, MPO, on labs.

Dr. Vojdani:                        Yes. Yes. Thank you.

Dr. Weitz:                            Somebody asked what is latent immunity? How long a period of time are we talking about?

Dr. Vojdani:                        Six months or longer.

Dr. Weitz:                            Okay, let’s see. Somebody was asking is there any way to verify if somebody had SARS COVID infection or if the antibodies that are found would be coming from the vaccine? I think is what the question is.

Dr. Vojdani:                        I think impossible. Impossible. Honestly, I don’t think so because if we accept that injection of RNA or spike protein results in the production of spike protein in our blood and our immune system is going to take that and will make antibodies against spike protein will be impossible to differentiate whether that antibodies is produced due to infection with SARS-CoV-2 or due to vaccination?

Dr. Weitz:                            Well, the antibodies to the spike protein, but what if they have antibodies to the nuclear receptor? That would only come from the virus.

Dr. Vojdani:                        Yes, yes, you are right. Absolutely, yes. If you do antibodies against nucleo protein and you detect that, that could be due to the virus and not due to vaccination. Thank you so much.

Dr. Weitz:                            Somebody asked, this practitioner said that he’s not practicing in the US or Canada. Do you periodically hold any online discussion forums with other expert colleagues where practitioners can join and learn about Cyrex?

Dr. Vojdani:                        Oh, I think we have webinars. We have many activities with PLMI, Personalized Medicine Institute. We have with RUPPA. So for example, I’m going to have one I believe on April on behalf of RUPPA and immunoscience lab. Yes, we have some of these activities and if Heather is with us to take the name of that individual and when we’ll have such activities, we should invite that individual to participate. I appreciate that.

Dr. Weitz:                            Somebody asked about the use of a nutritional supplement Monolaurin in inhibiting viral infections.

Dr. Vojdani:                        I think there is some anecdotal evidence, but I haven’t seen articles published in the hardcore journals that talking about some of these factors.

Dr. Weitz:                            Is there any truth to the concept of viral shedding?

Dr. Vojdani:                        Yes, it is.

Dr. Weitz:                            Okay, what do we know about it?

Dr. Vojdani:                        I think the viral shedding is the three steps that I showed that infection, replication and spread of the virus is viral shedding.

Dr. Weitz:                            Okay. Well, can that also come from the V?

Dr. Vojdani:                        From what?

Dr. Weitz:                            From the V?

Dr. Vojdani:                        Oh, from the B-cell?

Dr. Weitz:                            No, the vaccine.

Dr. Vojdani:                        Ah, from the vaccine. Okay. If we are introducing RNA, you saw that in the mechanism that when the virus first injects its RNA into the cells and the RNA becomes the whole cell by being surrounded by the membrane and then divides and spreads. I haven’t seen anybody talking about that, but that mechanism is possible.

Dr. Weitz:                            I’m just going through the questions. Anybody has any final questions? Just put it in the chat. Otherwise, we’re going to wrap.

Speaker 5:                           May I ask a question?

Dr. Weitz:                            Sure.

Speaker 5:                           Hi Dr. Vojdani. I was just wondering since for example, COVID vaccine is a little different from other vaccines. It doesn’t have a live virus, but it only has the RNA structure of the virus. That’s what I think it has. Would that also cause viral shedding or is it only when the live virus in a vaccine is present?

Dr. Vojdani:                        Like I said, I really don’t know. I didn’t read anything about this.

Speaker 5:                           Okay.

Dr. Vojdani:                        But is it possible? I believe it is possible, but there is no evidence.

Speaker 5:                           I see. Thank you.

Dr. Vojdani:                        Pleasure.

Dr. Weitz:                            Okay. So I think that’s the rest of the questions. Thank you so much Dr. Vojdani. I’ll share that article with everybody and this is being recorded and it’ll be posted on Tuesday so you can listen to it on the audio version or go to YouTube and watch the whole presentation.

Dr. Vojdani:                        Thank you Dr. Weitz.



Dr. Weitz:                            So thank you everybody and we’ll see you next month. And thank you for making it all the way through this episode of the Rational Wellness Podcast. And for those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcast or Spotify and give us a five-star ratings and review. That way more people will be able to discover the Rational Wellness Podcast. And I wanted to say thank you to all the patients that we’ve been working with at our Weitz Sports Chiropractic and Nutrition clinic who, many of whom, most of whom we’ve been able to help with a range of various health conditions from various types of gut disorders to thyroid and hormonal issues, autoimmune diseases and various other cardiometabolic conditions.  And so I very much appreciate you and I’m excited about going forwards, helping you to improve your health on your journey towards optimal health. And I wanted to let everybody know that I do have a few openings now for new clients and you can take advantage of that by calling my Weitz Sports Chiropractic and Nutrition Santa Monica office at 310-395-3111. And we can set you up for a new consultation for functional medicine nutrition, and we can get that going as early as the new year. So give us a call and I’ll talk to you next week.


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