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Covid-19 and Immunocompromised Patients

Covid-19 and Immunocompromised Patients

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. 

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. 

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.

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.

Dear Dr. K; Are you personally going to take the coronavirus vaccine?

Dear Dr. K; Are you personally going to take the coronavirus vaccine?

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. 

Covid-19 and Allergy

Covid-19 and Allergy

Harvard researchers recently published their findings regarding allergic disorders and susceptibility to Covid-19.  The study was conducted on 220,000 people between January and May of this year. 

Previous to this study it has been known that people at greater risk for and from this virus include those: over 65, with pre-existing lung disease, with chronic kidney disease, with diabetes, with hypertension, with heart disease, obesity, with cancer, smokers, with immune compromising illnesses, with organ transplants and with HIV.  Now it appears that underlying allergy also confers greater risk. 

It has been known for many years that underlying allergic respiratory problems predispose to other types of respiratory infections from colds, to ear and sinus infections to bronchitis and pneumonia.  It has also been known for years that treating the underlying allergy reduces this risk.  Now, it seems that allergy predisposes to both catching Covid-19 and having a more serious outcome.  People with either allergic rhinitis or asthma have this increased risk.  The scientists feel the increased risk from allergy is probably multifactorial, but one aspect recently discovered is an increase in one of the cellular attachment proteins: TMPRSS2.

In order to enter the human body Covid-19 has to use certain available “doors” called cell receptors.  The more “doors” available, the more readily the virus can enter.  Allergic inflammation increases the number of TMPRSS2 doors.

The researchers went on to speculate that having good control of the allergic condition (and thereby reducing the inflammation) should help reduce this increased risk. 

Q – Tips: COVID-19

Q – Tips: COVID-19

The two main tests being used during this pandemic are nasal swabs to detect active infection, and antibody tests to detect prior infection.    

The nasal swab uses a polymerase chain reaction (PCR) which is a chemical tool that amplifies tiny amounts of nucleic acid to allow detection of viral RNA.

Antibody tests fall into two main categories:  detection and protective value. The two main detection assays are for either spike glycoprotein (allows the virus to enter human cells) or nucleocapsid phosphoprotein (the most abundant protein).  Both can confirm a prior corona virus infection.  

Neutralizing antibody assay is used to determine if the presence of antibodies can “kill” (neutralize) the corona virus in a test tube.  This type of testing will be used to determine how effective corona virus vaccines will be.