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Author: Stephen J. Klemawesch, MD

Dear Dr. K; Any good news on Covid vaccines?

Dear Dr. K; Any good news on Covid vaccines?

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. 

Q-Tips: pollen allergy

Q-Tips: pollen allergy

We are currently in grass pollen season and soon to be added is ragweed pollen.  People with grass pollen allergy may have worse symptoms this time of year if they ingest foods that share allergenic components with the pollen.  These grass related foods are: melons, oranges, kiwi, tomato, and peanut.  Ragweed related foods include: melons, banana, artichoke, cucumber, zucchini, echinacea, chamomile and hibiscus tea.

Fluvoxamine for Covid-19?

Fluvoxamine for Covid-19?

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.

Mother and Fetus Get Well Together

Mother and Fetus Get Well Together

Hereditary Angioedema (HAE) is an inherited deficiency of functional C-1-esterase inhibitor (C-1-INH) and is characterized by unpredictable recurrent episodes of painful often disabling swelling of the abdomen or face or extremities. 

In the recent past several new drugs have become available to treat this condition.  One of the most exciting ones is Ruconest,

which is a C-1-esterase inhibitor made by recombinant technology.  Thus, it works by replacing what the patient fails

to make (or fails to make in a functional protein).  By way of explanation C-1-esterase inhibitor is a “gate-keeper” or “watch-dog” for inappropriate activation of our complement system proteins.  If the complement system is activated when it is not needed, it makes the individual sick by causing the tissue swelling which is the hallmark of HAE.

In women with HAE, variations in hormones such as the menstrual cycle or pregnancy can bring on attacks.  A case in point was recently published in the medical literature of a 23-year-old woman who experienced multiple attacks of angioedema during her pregnancy.  Because Ruconest is technically not a drug but a pure replacement protein it is felt to be safe to use during pregnancy.   At 38 weeks the woman had a severe attack as she was going into labor.  Because of concern for the fetus an ultrasound was done and the baby was also having an attack of facial angioedema.  The woman received Ruconest and as her swelling subsided so too did her infant sons swelling.  By the time he was delivered he was back to normal.  This is the first documented account of fetal angioedema successfully treated while treating the mother.

Catnip and Mosquitoes

Catnip and Mosquitoes

Neuroscientists at Northwestern University have made an amazing discovery about catnip, it repels mosquitoes and other insects.  The active component of catnip (Nepeta catoria) is nepetalactone which stimulates a neuroreceptor called TRPA1.  TRPA1 is found in most animals from insects to humans, and transmits pain sensation to the brain.  TRPA1 can also be triggered by hot, cold, and irritants. 

The interesting thing is that when applied to humans as a repellant it does not trigger a pain response in the human, nor does it trigger pain in felines.  In felines it triggers a different receptor involved in pleasure sensation. 

Work is underway to find an effective way to use nepetalactone in an easily applied skin vehicle to provide a non-DEET alternative for summer misery.

Circadian Cycles

Circadian Cycles

The New England Journal of Medicine recently had a review article on circadian mechanisms.  What was once thought to simply control sleep/wake periodicity and females’ monthly cycles is now known to control our complex physiology even down to a cellular level.  Also, they are not unique to humans but have been present in all life forms (plant and animal) for the past 3 billion years. 

This universal presence indicates that circadian cycles are critical for both fitness and survival of all species. 

In humans there are two types of circadian clocks: the master clock in the brain and individual clocks in individual cells.  In the brain, the main timepiece is found in an area comprised of about 20,000 nerve cells called the suprachiasmatic nucleus (SCN).  But, the key input to this area comes from our eyes via photo receptor cones and rods.  The input of light sets the pacemaker cells in the SCN to our specific cycle.  These pacemakers can only reset themselves by one hour per day.    Thus, travel across multiple time zones requires one day for each zone crossed to reset.  This is called jet lag.  But many people experience a similar disruption due to “social jet lag” which occurs when sleep time varies a lot due to work/school hours versus weekends. 

Another source of disruption occurs due to the frequent use of electronic devices such as computers and smart phones.  The blue light emitted by electronics has a very strong clock resetting effect. 

Individual cells contain clock genes referred to as CLOCK-BAMAL1 that regulate DNA, RNA and protein synthesis.  By so doing, cells will perform best at certain times of the day and poorly at other times.  This has important ramifications for our immune systems and allergy.  It has

been shown that allergic reactions are more likely to be severe when there is a dysregulated clock. 

Immune defense against infection can be similarly impaired. Inflammatory diseases such as inflammatory bowel disease and arthritis worsen with clock dysfunction.  Even immune protection against cancer is reduced in shift workers and in people with frequent alterations in circadian cycles.  This has been very clearly shown for breast cancer, colon cancer and prostate cancer.  Curiously, exposure to artificial light at night increases the risk for melanomas, independent of degree of sun exposure.  Also, morning sunlight is more likely to promote skin cancer development than sunlight later in the day.

So, I guess Tom Hank’s character Chuck Noland said it best in the movie Castaway: “We live and we die by time and we must not commit the sin of turning our back on time.” 

Topical Steroids & Bone Density

Topical Steroids & Bone Density

It has been known for a long time that systemic steroids can affect bone density.  This effect is both dose and durations of therapy related. 

Until recently, there has not been a good scientific study of topical steroids and bones.  Danish scientists recently Finished (pun intended) a 15-year study of 723,000 adults using topical steroids.  They found that long term use of medium or high potency steroids did contribute to the development of osteoporosis and also increased risk for bone fractures.   

CrossFit vs Crosswords

CrossFit vs Crosswords

By: Sasha Klemawesch, MD

A few years ago, I wrote about a potential vaccine for Alzheimers. We are still a while away from having one on the market, especially since the initial trials had to be aborted due to brain swelling and other unwanted side effects. (Don’t lose hope though, a new formulation is in development and undergoing clinical validation studies.)

But in the meantime, there are many non-pharmacologic things you can do to keep your brain healthy.

When asked, “What’s the best thing to do to keep your mind sharp and ward off dementia?” Most people (myself included) would answer “crosswords” or some other sort of brain teaser. Turns out…. Yes … and/but … No.

In his new book, “Keep Sharp”, Dr Sanjay Gupta discusses strategies for preserving brain function, and he talks about the myth of the crossword puzzle. If you are someone who does crosswords, or sudoku’s, or some other form of mental exercise every day, you might not be getting as much benefit from them as you had hoped. Over time it becomes a ‘practice-makes-perfect’ phenomenon, where your brain learns how to perform the task and therefore it is no longer a struggle to complete it. The key to enhancing cognitive function (at any age) is to challenge the brain. You want to create new neural connections and force it to forge new pathways. By doing so you literally and figuratively grow your brain size. But the only way to form new neuronal paths is to engage in new activities.

If you love crosswords, by all means, keep doing them. But add in different sorts of puzzles, like cryptograms or kakuros. Even better, do something physically stimulating rather than just mentally so. Physical activity is one of THE most important aspects of maintaining a healthy brain. And despite the name of this article, you do not have to start dead-lifting 300 lbs. or running triathlons. A little exercise goes a long way.

If you spend a good deal of the day watching TV, simply standing at each commercial – yes, just standing up – will have enormous benefits. Better yet, stand and do squats. If you are more a book reader, get up at the end of each

chapter and walk around the kitchen island 10 times or march in place for 1 minute. It might sound inconsequential, but those little things will add up. Even better than doing a few minutes here and there inside your house would be to get outside in the fresh air for a walk. And if you can do it with a friend, all the better. Dr Gupta calls that a “brain trifecta.” By (1) moving, (2) socializing and (3) destressing, you “measurably detoxify” your brain, and the spontaneity inherent to friendly conversations means your brain can’t anticipate what will come up during the interaction, so you end up engaging multiple regions of it. Also, research has shown that there is an inverse proportion between your risk of cognitive decline and the size of your social network.

Finally, don’t waste your time on supplements. There is no magic pill that can prevent cognitive decay. Eating a healthy balanced diet with lots of fresh fruits and veggies, while limiting refined sugar and saturated fats will get you the antioxidants and brain food you need.

Antibodies after Covid-19

Antibodies after Covid-19

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. 

COVID Vaccine in Older Adults

COVID Vaccine in Older Adults

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.