Hi Dr. Jeffrey Mark here. I was originally going to just share with you two recent studies that may shed some light on the question of why some people with SARS COV-2 develop a complicated course that requires hospitalization and have higher risk of death while others do much better. The studies show that genetic mutations and autoimmune antibodies can result in lower levels of interferon in people with viral infections. But, since I’ve had questions and concerns I wanted to comment on the breaking news of about President Trump and his COVID-19 treatments first.
His medical team has reported that within 72 hours of contracting the disease, President Trump had a fever, mild shortness of breath, and fatigue. He has been given Remdesivir, 8mg of Regeneron’s monoclonal antibody, and been flown to Walter Reed Army Medical Center for close observation. We had a discussion on monoclonal antibodies including Eli Lilly’s monoclonal antibody, a sister monoclonal antibody to Regeneron’s antibody in our update 2 weeks ago in Optimize Your Energy Part 4 and Pandemic Update. Fortunately, President Trump has reportedly been taking Vitamin D, Zinc, and Pepcid. We’ve discussed the many benefits of vitamin D including optimizing the immune system, antioxidant properties to protect against oxidative stress and free radical damage, and helping avoid dysfunctional clotting formation. With Zinc, we discussed the suppression of viral replication but you need a zinc ionophore like Quercitin. We didn’t discuss Pepcid but there is a retrospective observational study by Dr. Raymond McKay, a cardiologist at the Hartford HealthCare (HHC) Heart & Vascular Institute, called the “Famotidine (Pepcid) Study,” which recently released data based on 900 hospitalized HHC patients that showed patients taking Pepcid were 45 percent less likely to die in the hospital and less likely to have combined adverse outcomes leading to death. The patients were also 48 percent less likely to need help breathing from a ventilator. Pepcid use also led to lower levels of inflammatory markers in the study.
There have been many comments on some disparities with details given from the White House Staff Physician Sean Conley and chief of staff Mark Meadows but by evaluating Mr. Trump’s overall risk factors he is in the higher risk category. We know from his publically released White House physical on June 3rd, 2020 at age 73, height 6 foot 3 inches and weight of 244 lbs he has a body mass index just greater than 30 putting him in the obese category. He had a blood pressure of 121/79 with a pulse oximetry of 98% on room air on that examination. We know that there is a 5 times higher risk for complications including hospitalization from age group 65 to 74 as compared to people aged 18 to 29 from a study published by the University of Cambridge. There is a 90x higher risk for death. The estimated risk of death at age 74 would be 4%. Presently , he has the additional risk factors of being male and overweight which further increases the 4% chance of death for just being age 74. President Trump is currently in the 2nd phase of the coronavirus infection. Phase 1 includes the time from viral exposure to viral detection, then progression to maximal infectivity with or without symptoms. In phase 2 , the immune system begins to react to the virus and hopefully there is an appropriate reaction including the secretion of interferon, which will we will talk more about in a minute, and then in the ideal case a drop in the viral load or titers or the amount of virus and a tapering of the acute or immediate inflammatory process as the virus load is being reduced and slowly cleared. If the immune system has trouble clearing the virus or thinks it has trouble clearing the virus it can go all out and even has the equivalent of a "nuclear option" which can cause a cascade of damaging oxidative inflammation including the cytokine storm and bradykinin storm, which we've discussed before. The earliest sign of the immune system inappropriately responding to the infection is progressive shortness of breath and a drop in the oxygenation level. Oxygenation should be above 92% and if the pulse oximeter drops below 90% then supplemental oxygen is given. Depending on the institution, Remdisivir may also be given if there are signs of increasing shortness of breath or decreasing oxygenation levels. In President Trump’s case he was given Remdisevir and an 8mg dose of Regeneron's monoclonal antibody. It was mentioned that he had drops in his oxygenation although to what degree and for how long is not clarified. We did learn over the weekend he has started a 5 day regimen of Dexamethasone. This is usually reserved when there is a persistent need for supplemental oxygen but before progression to ventilator support. In the President’s case it may have been given him just being overly cautious in the most optimistic viewpoint but this does bring concern if there was the usual indication for the Dexamethasone. Unfortunately, the details are incomplete so one cannot say. The next twenty four to forty eight hours will be critical. Hopefully, his immune system with the assistance of the Remdesivir and monoclonal antibody will bring down the viral load significantly and start to decrease an overly aggressive inflammatory response from a taxed desperate immune system that may be starting to throw everything it has at a virus it may have trouble clearing.
Usually people are in phase 2 for 7 days and at the end of that time, 80% of people’s immune system would have succeeded to clearing the virus and beginning to ramp down on the inflammatory response while continuing to produce high levels of antibodies against the virus. Unfortunately for the other 20% there is a progression to phase 3 with hospitalization and higher risk for ventilation, ICU, and death. For over the past 6 months physicians and scientists have struggled with the question of why some people with SARS COV-2 develop a complicated course that requires hospitalization and have higher risk of death while others do much better. We discussed how low vitamin D levels and lower glutathione levels may contribute but now there are 2 studies one of which can account for 14 % of these complications and deaths.
An article in Science described these studies. The role of interferon was first explored in the paper entitled “Interferon Responses could Explain Susceptibility to Severe COVID-19”. By Dr. Nancy Gough, PhD. It hypothesized how impaired or delayed antiviral signaling could be a treatable cause of serious COVID-19. Interferons are made by cells to tell each other that there is an invading virus and it also inhibits its spread and kills the virus by activating certain proteins and the immune system. Uninfected cells outside the body can detect the virus and produce interferon. Cells inside the body and even infected cells can procedure interferon. There is a type 1 interferon and type 3 interferons. The type 3 interferon tells epithelial cells to turn on antiviral genes. The concern is that SARS COV-2 could block genes to turn on the interferons and therefore block the antiviral genes from turning on. 2 papers now support this hypothesis. The first was published on September 24, 2020 entitled “Inborn errors of type 1 interferon immunity in patients with life-threatening COVID -19 by lead author Qian Zhang in Science. A gene mutation was present in many patients with severe COVID-19 . Human fibroblasts that had these genetic defects were vulnerable to COV SARS-2 because they could not make TLR3 and IRF7 dependent type 1 interferon. The other paper was entitiled “Auto-antibodies against type 1 interferones in patients with life – threatening COVID -19 by lead author Paul Bastard also published on September 24, 2020 in Science. This study found that as we get older we make antibodies that actually bind to type 1 interferon and therefore neutralize the ability of the corresponding type 1 interferones to block SARS-CoV-2 infection and present in only 4 of 1,227 healthy individuals. The auto-Abs neutralize lFN-alpha 2 and IFN-gamma. In healthy people these antibodies were not present. When you have any of the autoantibodies there are much lower levels of interferon. Therefore , in order to have optimal interferon levels and function during a viral infection you cannot have a mutation or auto antibodies. The 20 % after the 7 days spent in phase 2 that go on to more complications and hospitalization may not have adequate interferon levels or innate immune response. Supplemental interferon may be considered and I’ve used supplemental interferon over 20 years ago when that was we had to treat hepatitis C. Ways to enhance interferon production include hyperthermia. There is paper published May, 1988 in the Journal of Interferon research entitled “Hyperthermia in Humans Enhances Interferon gamma synthesis and alters the peripheral lymphocyte population.” Therefore, we should be careful not to initially suppress the fever from a viral infection as to allow the body to produce as much interferon that it can to fight the virus.
So for people including President Trump, with COVID-19 in Phase 1 or 2, my recommendations are to get plenty of rest, avoid treating the fever for the first 24 hours if possible, and to take supplements. We’ve previously discussed about the benefits of Vitamin D, Zinc, Quercetin, N-acetyl cysteine or Glutathione which are among the other supportive nutrients found in products such as MitoMax, Immune Defense, and ViraX.
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Take Care and Stay Healthy.
Jeffrey Mark, M.D.