Thank you for keeping an open dialogue with me about Covid vaccines. As you know, I opted against vaccination. However, over Christmas I caught Covid, but luckily it was a mild flu like illness. So, I guess I should be OK from here on out.
I’m glad your illness was mild, but I’m a little hesitant about predicting how things will play out in the future. First of all, just as vaccination doesn’t provide iron-clad protection so too natural immunity via infection is not 100% effective in preventing re-infection. Therefore, with the extended nature of the pandemic, following Covid avoidance precautions still makes sense.
Another concern I have is the frequency of post-Covid sequelae especially neurologic ones. By now, the general public is well aware of Covid illness’ predilection to impact the sense of taste/smell. As it turns out, this is just the tip of the proverbial iceberg. At this point in the pandemic, it seems that roughly 70% of infected individuals suffer some sort of extended neurological issue. For many it’s the smell/taste scenario and for others protracted headaches. Of much graver concern is research done by Oxford University on 45,000 people in the UK which showed loss of brain mass as measured by CT scanning. The loss was primarily in the frontal and temporal lobes which subserve the senses of taste and smell but also cognition.
In this regard, the Oxford scientists conducted performance tests on some of the Covid patients and found they were slower in processing information than non-infected counterparts. Also, there was no correlation between the severity of the illness (hospitalized verses non-hospitalized) and the loss of brain matter.
These facts set up a comparison with Alzheimer’s disease where a common symptom is loss of sense of smell along with frontal/temporal lobes pathology. In fact, some neuro scientists posit that Alzheimer’s disease is caused by chronic inflammation in genetically susceptible individuals to a prior viral infection. What isn’t known is the potential for brain mass recovery in these individuals. Neuroplasticity allows marked recovery of the brain from many insults. Perhaps this will still be true with “Covid brain”. But for now, I think it’s still best to not catch the illness.
Ivermectin in an FDA approved drug for the treatment of intestinal strongyloidiasis (round worm) and onchocerciasis (filarial worm). It is also used in veterinary medicine to treat parasites in pets and in livestock.
Because of significant use of Ivermectin off label to either try and prevent or to try and treat Covid, scientists have scrutinized its potential. Of interest in vitro (in a test tube) Ivermectin does inhibit replication of the virus. Unfortunately, in vivo (in actual patients) multiple studies have confirmed that it fails to either prevent Covid or treat Covid. Despite these scientific facts, thousands of Americans have taken Ivermectin for Covid. These individuals obtain either veterinary Ivermectin or prescription Ivermectin.
This wouldn’t be a problem if Ivermectin were a perfectly safe drug. Unfortunately, that isn’t the case. Oregon Health and Science University recently reported in the New England Journal of Medicine a plethora of cases of Ivermectin toxicity.
The usual treatment of Strongyloides is 12 to 14 mg either one time or twice. But some individuals using the drug for Covid are using much larger doses and for longer periods of time. The University of Oregon has compiled a study of Ivermectin toxicity. To date no one has died, but there have been many patients hospitalized and many requiring ICU care for their toxicity. The majority of these individuals were using veterinary products without prescription guidance. Some were taking as much as 100 to 125 mg a day. The main toxic effects were gastrointestinal, cardio vascular or neurologic. The neurologic side effects included generalized weakness, ataxia and seizures.
As the Covid pandemic continues it is critical that good scientific inquiry and open-mindedness prevail. But at this point in time good science indicates that Ivermectin is not helpful and can be harmful.
The FDA has recently approved (emergency use authorization) two oral antivirals and a monoclonal antibody for Covid.
The antivirals are designed for out patient use in mild to moderate Covid-19. Both have proven to be active against the original Corona virus and its new variants.
Paxlovid uses two agents: nirmatrelvir (a viral protease inhibitor) and ritonavir (a CYP3a inhibitor). The treatment is for 5 days and can be used down to the age of 12.
Lagevrio contains molnupiravir a nucleoside analog that can be used down to 18-year-olds but not in pregnant women. Again, it is a 5-day treatment.
The monoclonal therapy is Evusheld and it contains two long lasting (6 months) antibodies: tixagevimab and cilgavimab. It is not a vaccine but a prophylaxis for people who are immune compromised (whether or not they have also been vaccinated) and for patients who can not receive one of the existing vaccines.
Many immunocompromised individuals have a poor response to the vaccines and Evusheld provides an additional method of protection.
My sister is on a JACK medicine for her ulcerative colitis but she said it may soon be used for allergies. Is that true?
Well, kind of. First of all, not to be too picky but there is a whole family of JAK drugs and the “JAK” refers to Janus kinase which is a pathway that transmits signals across cell membranes. The JAK system plays important roles in embryonic development, stem cell development, blood cell production and inflammation signaling.
This last role is why it can be targeted to prevent inflammation, because left to its own devices it transduces signals from cytokines (chemical messengers) into cells leading to inflammation. I’m pretty sure your sister is taking tofacitinib which is also being used to treat rheumatoid arthritis and most recently Covid-19.
You might have heard about a phenomenon in severely ill Covid patients called cytokine storm. Basically, these particular individuals have an unbridled inflammatory response to Covid which causes the severe lung inflammation. Tofacitinib has saved the lives of thousands of ICU hospitalized Covid patients by abrogating this “over the top” inflammation.
But to get to the point of your question, the JAK system has great potential to help a myriad of allergic conditions. Just as Covid related cytokine storm, and autoimmune diseases such as your sister’s rheumatoid arthritis are due to failure to properly regulate the immune system, so too is allergy.
The currently available JAK drugs are taken orally and therefore work systemically. Because of their systemic nature there is some potential for untoward side effects such as immune suppression. The research on JAK’s for
allergy has focused on site delivery either by inhalation to treat asthma or by skin application to treat eczema. Research on both of these applications is very promising. In fact, the FDA just approved the first topical JAK for treating eczema: Opzelura (ruxolitinib cream). For both asthma and eczema, the JAK drugs will provide an alternative to steroids to treat the inflammation that causes both conditions.
There is still much to learn about Corona virus. One area that is particularly problematic is how to protect patients that are immunocompromised (roughly 5% of the US population) due to organ transplant, auto-immune/rheumatic diseases, cancer, and dialysis.
It has been long understood that the efficacy of many vaccines is attenuated in immunocompromised patients and this also seems to be the case for Covid-19 vaccines. Timing of the vaccine is important and it should be administered between chemotherapy cycles. For patients with stable rheumatology conditions suspending daily doses of mycophenolate and methotrexate for 1 to 2 weeks is advised.
A very small study has been done on administering a third dose of the m-RNA vaccine or administering the Johnson & Johnson vaccine to patients who already received two doses of an RNA vaccine. In the patients who had only very low antibody titers after their first two m-RNA vaccines, 100% developed excellent titers after a 3rd vaccine. However, in the patients with no detectable antibodies after their first two m-RNA vaccines, only 25% developed high antibody titers. Much larger study trials are underway to better address this issue. For the time being as America is unmasking, the previous guidelines for mask wearing and social isolation are still advised for immunocompromised patients.
The answer is yes: they are working well and luckily the foibles are generally mild. Globally there are eleven different vaccines currently in use, but so far only 2% of the world’s population has been vaccinated. We need to do better, including vaccines that don’t have elaborate requirements for transport or refrigeration. Another 251 vaccines are at some stage of development including 60 that are entering human trials. Let me tell you about some of the very promising ones.
Vaxxinity Pharmaceuticals has created a vaccine using proteins from the Corona Virus spike protein that are the ones that allow the virus to attach to and invade human cells. Another company, Novavax, has also developed a spike protein vaccine but theirs is directed to the entire protein, not just the “latch-on” portion. Both vaccines are very promising and early trials indicate they will work against corona variants.
Vaxart Pharmaceuticals had developed on oral vaccine that uses the common cold virus (adenovirus) to carry pieces of the corona virus through a hybrid technology. Johnson and Johnson and AstraZeneca use the same technology in their injected vaccines which work very well.
There are two big advantages for an oral vaccine. One is that it is easily administered, not requiring refrigeration. The other is a dual protection mechanism. Oral vaccines, uniquely, provide both “blood stream” protection (as do all injected vaccines) but also mucus membrane protection. Oral vaccines lead to antibodies being present on the mucus membranes of the nose,
mouth and lungs as a first line of defense against the virus. Historically there was a similar segue for polio vaccines from Dr. Salk’s injected vaccine to Dr. Sabin’s oral “sugar cube” vaccine.
Another advantage of Vaxart is that it elicits an immune response to both the spike protein and the N protein on the Corona virus (Johnson and Johnson and AstraZeneca only elicit spike protein antibodies). This may be important for mutant variants because they alter the spike protein much more rapidly than the N protein.
Valneva Pharmaceuticals is using a killed whole virus vaccine with two adjuvants (substances that enhance immune response). Several killed virus vaccines are already in use (made by Sinopharm, Sinovac and Bharat Biotech) but they do not include the immune booster adjuvants.
Inovio Pharmaceuticals uses a DNA vaccine that is injected just under the skin with multiple tiny needles and then zapped into cells via a handheld wand that releases a split-second pulse of electricity. From there the cells produce the spike protein which cues an immune response. No other vaccine uses this delivery system. So far, patients report much less discomfort from the vaccine and also fewer side effects. Since the vaccine consists of only DNA and saline it can be stored at room temperature.
Many drugs have been considered for treatment of Covid-19 and several monoclonal antibodies have been granted emergency use authorization by the FDA. However, the only FDA approved drug for treating Covid-19 is the IV antiviral Remdesivir that inhibits RNA polymerase.
Fluvoxamine is one of many SSRI’s (Selective Serotonin Reuptake Inhibitors) that are used to treat anxiety and depression. However, Fluvoxamine is structurally unrelated to the other SSRI’s. In addition to its serotonin modulating activity, it is a strong agonist (stimulator) of sigma-1 receptors in the endoplasmic reticulum.
Sigma-1 receptor stimulation has been shown to limit SARS-COV-2 replication and to modulate the inflammatory response to sepsis in animals. It is the overwhelming inflammatory response called cytokine storm that causes the life threatening acute respiratory distress syndrome in Covid-19.
So far, two very small studies in humans have been very promising. In a double-blind study of 152 people with Covid-19, ½ received fluvoxamine and ½ placebo. Clinical deterioration occurred in none of the fluvoxamine recipients whereas 6 of the placebo group deteriorated.
A second non-placebo-controlled study was done in 113 people with Covid-19. The participants were free to choose taking the medicine or not. Of the fluvoxamine receivers (65 in number) all were well after two weeks. In those not accepting the drug (48 in number) six were hospitalized, two were on ventilators and one died.
Now these are very small trials, so good science requires expanded studies. Right now, there is a large placebo-controlled trial under way which should be completed by September.
Two recently completed studies on people who sustained mild (non-hospitalized) infections with Covid revealed good immune response for the three months of the study. The recovered patients had both lymphocyte and antibody immunity to Covid. This is good news. What isn’t known yet is how long this immunity will last. Studies are ongoing in this regard.
Development of safe and effective vaccines for Covid-19 have been a global priority for thousands of scientists. Most of the participants in the varied trials are young and middle-aged adults. This has led to a concern that the good results in younger adults might not apply to older adults. Older age is a major risk factor for individuals having more severe disease and fatal outcome. It is also known that in general older adults do not have as robust an immune response to vaccination as do younger adults.
Emory University just completed a study of the m-RNA-1273 vaccine in older adults with their results being published in the New England Journal of Medicine. They looked at two age groups: 56-70 years, and greater than 71 years. Both groups received the recommended initial dose followed by the booster dose 28 days later.
The laboratory markers that were analyzed were assessment of T-cell response, and assessment of neutralizing antibody production. Both T-cells and antibodies are critical in providing protection against Covid-19. As it turns out, both age groups had excellent responses in their T-cells and antibodies.
The other parameter that was studied was adverse events, including: arthralgia, fatigue, fever, chills, headache, muscle ache, nausea, local reaction at injection site, and pain at injection site. First of all, there were no serious adverse events. Secondly, the side effects were similar in both groups with two exceptions: the 71 and older group were more likely to experience fatigue and fever than the 56-70 age group.
These results should be a source of reassurance and comfort to all those baby-boomers out there.
Yes. And let me tell you why. In 1720 the average life expectancy in this country was 25. A hundred years later in 1820 it was 41. Then in 1920 it hit 54. Currently it is in the mid-70’s. Despite all the marvels of modern medicine from antibiotics, to trans-vascular heart surgery, to organ transplantation, the major reasons for this improvement in life expectancy boil down to the big three S’s: sanitation, shoes, and shots.
It is hard to believe but the “why didn’t I think of that” realization that the sources of drinking water should be kept separate from human and animal waste is very recent. It came with the scientific discovery of microbes (viruses and bacteria) and how they are transmitted.
Then the universal use of footwear came into play. Prior to that innovation a majority of humans went bare-footed for at least part of the year depending on climate. As a result, most humans picked up worm infestations through their bare feet that found their way to the intestinal tract: hookworms primarily, but also other species. Once the worms set up housekeeping in the GI tract, they were there to stay (until the person died). Their presence affected health in two ways: reducing available calories and vitamins from food intake, and by causing chronic anemia.
The final “S” is shots, as in vaccines. In 1798 Edward Jenner developed smallpox vaccination. About 90 years later Louis Pasteur, often called the father of immunotherapy, developed anthrax and rabies vaccines. It wasn’t until 1924 that Emil Von Behring developed the tetanus vaccine. The polio pandemic was stopped in 1955 when Jonas Salk developed the polio vaccine. Prior to vaccines, those five diseases killed countless millions of children and adults.
It all comes down to the old adage of “an ounce of prevention is worth a pound of cure”. Sanitation, shoes, and shots all work by preventing illness. So, yes, I will get the coronavirus vaccine.