The End of Monoclonal Antibody Treatment of COVID-19

National Public Radio (NPR) reviewed the end of the outpatient use of monoclonal antibodies to combat SARS 2 Coronavirus (COVID last week. These synthetically produced antibodies were infused into patients infected with COVID and were at high risk to develop severe disease requiring hospitalization or death. It cost about 200 million dollars to invent, develop and then use the drug in trials to gain FDA approval for human usage. Drug manufacturers were willing to take the risk developing these products because the US government financially guaranteed their purchase.

The antibodies were synthetic Y shaped molecules which bound to the viruses spike protein rendering it incapable of invading human cells and alerting our own immune system that the virus was present facilitating the virus’s destruction. Over time, the virus learned to mutate and evade a particular monoclonal antibody rendering it ineffective. When 30% or more of the new COVID variants in a region became able to resist the monoclonal antibody, the CDC and FDA withdrew the product. Drug manufacturers continued to develop new monoclonals due to the Federal guarantee of purchase.

Bebtelivimab was the last product that worked well against COVID and on Monday, November 21, 2022 it was withdrawn as well. The Federal government stopped guaranteeing purchase of these products so drug manufacturers have now discontinued their expensive development.

Let me explain how this impacts my patients locally. Baptist Health BOCA Raton Regional Hospital had a robust outpatient monoclonal antibody program. I phoned or text messaged Lisa, the nurse practitioner program director the patient name , demographics and reason for participation and she scheduled and her team administered the drug within the seven day window required. No one became ill from the infusions. No one had to stop their usual medications due to drug drug interactions. No one progressed to severe disease requiring hospitalization and no one died. I referred at least 100 high risk patients including myself in the last 2.5 years and now that weapon is gone. No one treated cleared the virus and then had a rebound recurrent period of sickness.

So we are now left with Paxlovid and Lagevrio oral pills. One has multiple drug interactions with so many of the common medications the high risk population takes daily for cardiac, renal , diabetic and mental health it requires cessation or a reduction in dosage. The other is just not that effective. Patients taking these drugs also at times clear the virus then several days later have a mild rebound of symptoms and are contagious for a few days more.

We head into winter with an aggressive flu bug, respiratory syncytial virus in epidemic proportions and one less successful weapon against COVID-19. As I reflect on this past Thanksgiving holiday, I am grateful for the BRRH monoclonal antibody team and everyone connected with its development. I wonder what our elected Congressional officials were thinking when they stopped funding the development of these effective and safe, but expensive, products?

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COVID-19 Burnout

I was supposed to be visiting the NY Metropolitan area this week to celebrate a family high school graduation. Children and family were traveling from all over the country for this celebration when the parents of the graduate contracted COVID-19. The graduate stayed healthy and attended the ceremony and all post ceremony celebrations. Our family gathering was postponed, and my wife and I stayed home cancelling our flights and hotel reservations. The infected group were all vaccinated months ago and young, healthy and placed on Paxlovid . They are recovering. The fact that all will recover is what is important in a scene played out in homes across the globe all dealing with COVID and family gatherings.

At the same time this was occurring the FDA approved a Pfizer three-shot vaccine and Moderna two-shot vaccine protocol for COVID for children six months to five years old. It provided great joy in my south Miami daughter’s household since her four-year-old son has been attending pre-school and summer camp with no real protection other than a mask. My grandson has been the only child in his class and group wearing a mask indoors and the school psychologist asked my daughter if he could remove it because it was a barrier to playing with the other children.

The vaccine for young kids is not a foolproof shield but at least provided protection against serious illness. The FDA approval was a great comfort to parents hoping to have their kids vaccinated prior to the start of the next school semester in August. Then, the Governor and Florida Surgeon General announced Florida was not ordering the vaccine because they believed healthy kids did not need it despite all the infectious disease, public health and virology experts reviewing the data and approving the vaccine. Morale fell to a new low.

The very next day the Governor announced that doctors and pharmacies could order the vaccine through the Florida Shots website and had that option all along. That is not the way we ordered the vaccine earlier in the pandemic. We ordered it though the Florida Department of Health.

Supporters of the Governor blamed this ordering confusion on “big government bureaucracy”. If that is the case, then why not just announce from the beginning that pharmacies, doctors and health systems can order the vaccine through the Florida Shots website?

In the political gamesmanship of placing barriers in the way of our youngest and most vulnerable children being vaccinated, did the Governor forget that most physician offices do not have freezers capable of storing the vaccine at -90 degrees Centigrade? Also ignored was the plight of those who have relied on their county or city health department to provide the vaccines for their children for years and now those public health facilities will not have the vaccines.

My office was bombarded this week with calls from patient’s testing positive for COVID-19, all with mild symptoms of fatigue and upper respiratory viral symptoms. The current treatment options are to supply supportive care such as fluids, cough medicine, Tylenol and rest or prescribe the Pfizer pill Paxlovid. The Paxlovid must be started within five days of onset of symptoms.

So many patients walk around with cold symptoms for several days before home testing that it’s difficult to start the medicine within the five day window advised by the manufacturer. Paxlovid interacts with so many popular and common prescription medications for seniors which must be discontinued and washed out of your system prior to starting Paxlovid that they can’t start the medication on time.

The best option, in my opinion, remains receiving an infusion of the monoclonal antibody Bebtolivimab within seven days of onset of symptoms. Boca Raton Regional Hospital has a program that gets you in within a few days but several patients have been so anxious and worried that they would not wait for an appointment. Several called private services to come to their homes and treat them with monoclonal antibodies. These companies have popped up out of nowhere and their reputation and reliability are relatively unknown. Are they really administering Bebtolivimab? At least at the hospital I know the product is the real thing and the monitoring staff is well trained and experienced.

Also, several patients have insisted on Paxlovid and stopped their blood pressure, cholesterol and antidepressant medicines. Two of them took the Paxlovid and improved, then rebounded with a positive test and return of all symptoms several days later. They all recovered in a few days, but the potential rebound is another reason I prefer offering the monoclonal antibody infusion.

I have not mentioned the Merck oral medication Lagevrio ( molnupravir) because it used new technology involving disrupting the genetics of the virus. I would like to see the adverse effects of this drug and its efficacy and safety profile after being on the market for twelve or more months prior to considering it.

COVID remains a “bummer”. We are in a much better place to prevent serious illness than we were three years ago but human behavior, the demonizing of science for political gain and the resilience of this virus continue to wreak havoc on my life and those around me.

Disappointment in Decision-Making Regarding COVID-19

I received an email from the Chief Medical Officer at my main local hospital informing me that elective surgical and diagnostic procedures had been cancelled due to understaffing because of COVID-19 infections. He mentioned 136 employees testing positive yesterday and 36 nurses not reporting to work this morning for the day shift due to COVID. Nearby Holy Cross Medical Center has stopped delivering babies due to a shortage of staff.

I subscribe to numerous physician run newsletters that discuss expert opinions on many specialty topics. The physician writers are all at the stage of life where they and their children are young and they are grappling with in-person schooling and infection. They write about hosting large holiday gatherings and now learning that multiple attendees are ill and positive with COVID-19.

While there have been few hospitalizations so far in this young professional vaccinated group, they worry about infecting their young unvaccinated children and elderly parents with chronic illnesses. These are leaders in the health care public policy and influence pedaling industry today and their lack of discipline and ability to delay gratification has put us all in the unenviable position of having to face an absence of available medical services due to further spread of COVID-19

I have no more success with my own highly educated children who do not work in health care. My eldest child hosted a holiday gathering in Venice, California to celebrate their Christmas Canal Boat Parade and multiple attendees reported being sick four days later. She then boarded a plane to New Mexico with friends.  Upon their return, two of the three travelers are home with COVID-19

We are in a major surge of infection with a highly transmissible virus. Texas Children’s Hospital is full of children too young to be vaccinated and struggling to breathe and survive. Locally, Jack Nicklaus Children’s Hospital and Joe DiMaggio Children’s Hospital are facing similar problems.

I urge you to stay home. Wear a mask if you go out in public which is a N95 or KN95 mask or triple layer cloth surgical mask. Avoid eating out at restaurants even outside. Stay out of gyms. Stay out of country club dining rooms and card rooms. “The Board” can make those places clean but they can not make them safe from a respiratory virus with twice the transmissibility of smallpox and measles. The economy will suffer but can recover with intelligent leadership. Sadly, businesses will suffer too but they can recover. Lost children and seniors cannot be replaced.

Should I Measure My COVID Antibodies?

On a daily basis I get asked by patients to please add an antibody test to their necessary blood work monitoring chronic conditions and medications to see if they have immunity against COVID-19. Some want the information just to feel comfortable that they have responded to their vaccine administration. Some have had COVID-19 and want to see if their immunity is sufficient to avoid taking a COVID-19 vaccine or booster shot? Some who have not been vaccinated and have been ill recently but not tested just want to know if the illness was COVID-19.

The topic was just reviewed in the online journal MedPage Today. First of all, the test you order to determine if you developed immunity based on receiving the vaccine is different than the test you order to measure antibodies arising from a previous infection. Nathan Landau, PhD, a virologist with the NYU Grossman School of Medicine believes we do not yet have the data to determine if antibodies we develop from infection or vaccination are appropriate to provide immunity. “The real answer is we just don’t know. It takes time to gather that data, to know what titers people have and what their chance of getting infected is.”

To determine the level of antibody that is needed to prevent infection scientists must first perform neutralization assays or tests. These are not performed in the commercial labs that do antibody tests for COVID-19. The neutralization assay is the Gold Standard . The test is performed by taking the blood of an infected individual, isolating the blood serum and then diluting it into different strengths. The different strengths are then mixed with the live Sars2 Coronavirus in a set amount. They then observe if the virus is killed off.

 In order to kill the virus you must have neutralizing antibodies. The commercial labs only measure the total antibody not specifying how much of that is actually successful in neutralizing the live virus. The neutralization assay looks to see what dilution of the antibody kills off 50% of the virus.

For example a dilution of 1:100 means 1 milliliter of serum was mixed with 99 milliliter of saline. At this point we do not know what dilution is necessary to prevent infection. This data is known for diseases such as measles, German measles and different strains of hepatitis.

There has just not been enough time yet to make this determination but the research is ongoing and conclusions should be released soon. What is known is that the mRNA vaccines produce more immunity than the non mRNA vaccines. They also know that the antibody produced from a vaccine is superior to the immunity from infection against new variants and reinfection. The commercial tests are expensive, time consuming and use reagents affected by supply chain problems.

Relief From Migraine Headaches Erenumab (Aimovig) versus Topiramate

Patients with frequent migraine headaches, which disabling symptoms, were in the past treated with oral medications called beta blockers such as propranolol or metoprolol to prevent recurrences. Drugs such as amitriptyline (Elavil) and other antidepressants were used as well. Triptans, caffeine, acetaminophen, narcotics, and Ergot alkaloids rounded out the therapy. The headaches could be crippling and disabling for suffering patients. In recent years, physicians have added topiramate (Topamax) and injectable Aimovig (Erunumab) to the regimen.

Recently a double blinded controlled research project looked at 777 adults with at least four migraine headache days per month. To be in the study these individuals needed to have never been treated with migraine medications. Patients were randomly assigned to receive either Aimovig 70 mg, the 140 mg injection monthly or topiramate at a dosage of 50- 100 mg per day.

The study ran for twenty-four weeks. This was a phase 4 head-to-head study of the efficacy of one versus the other (Clinical Trials.gov Identifier: NCT03828539. The endpoints were at least a 50% reduction in monthly migraine days plus ability to remain in the study without leaving due to side effects from the medication.

The results and conclusion were that Aimovig injections resulted in fewer migraine headache days per month and less discontinuation due to side effects of the medication. Only about 11% of the Aimovig patients stopped the drug due to side effects (fatigue, nausea, disturbance in attention and dizziness) versus almost 40% in the Topiramate group (parasthesias, disturbance in attention, fatigue, and nausea).  The Aimovig group had a 55.4% of its participants achieve at least a 50% reduction in monthly migraine days compared with 31% in the topiramate group.

Patients with recurrent and severe headaches need a full neurological evaluation to determine the exact cause and type of headache they are experiencing. Once the cause and type of the headache are known, it is wonderful to have this calcitonin gene-related peptide receptor antagonist available to prevent migraines in sufferers of these severe headaches.

Omicron the new COVID Variant & the Pandemic

Last week my office staff and I met to discuss loosening some of our COVID-19 precautions due to the low positivity rate in the area and the vaccination status of the local population. We all enjoyed the return to normal this Thanksgiving inviting family to celebrate with us for the first time in two years. My children, their spouses and kids all flew home for a joyful few days. Then came news of a new variant out of South Africa, Omicron.

It is too soon for scientists to know very much other than structurally there are multiple mutations on the P-spike. It is felt that this makes the virus more transmissible than previous versions including the Delta strain.

We don’t yet know if the Omicron variant will produce more severe illness. It is too soon to know the incubation period and most significant period of disease transmission. We do not know if the COVID-19 vaccines will work against Omicron or if it will dodge our immune response. Nor do we know if it will bypass the immune response of those previously infected? I expect it will take at least three weeks to get some of the answers but probably three months to have a better idea.

The travel restrictions imposed by world leaders are too little and probably too late. Banning foreign nationals from entering your country while permitting citizens to return assumes the virus recognizes national flags and only infects foreign nationals. This decision is an outrage. Returning citizens need to be tested frequently while being quarantined for about 14-days. That is the type of travel restriction required. It is highly probable the new strain is already in the USA.

We need mass testing to start again so we can identify infection quickly and we need the lab capability to identify the infecting viral strain. In the meantime, while we learn about what we are dealing with, we need to once again wear masks, keep our social distance and avoid crowded indoor venues.

My practice will continue to screen patients over the phone and at the door. We will limit entry into our office and require masks to be worn. We will stagger patient visit times so that patients coming and going are not in close proximity. If necessary, we will return to telehealth visits only.

On the bright side, we are much more prepared for a new surge than before. More individuals are vaccinated and boosted. The COVID treatment pills work via a mechanism that is independent from the genetic mutations on the P-spike protein. Vaccine manufacturers have already begun preparing a vaccine against the Omicron strain that will take three months to reach the market. It is disheartening to face this crisis again, but we will, and hope the knowledge we need to acquire is learned quickly.

Vitamin D & Autoimmune Disease

Karen Costenbader, MD, of the Brigham and Women’s Hospital in Boston reported at a plenary session of the American College of Rheumatology that adults taking 2000 IU of Vitamin D and one gram of omega 3 fatty acids daily were less likely to develop autoimmune disease than adults taking a placebo. Costenbader’s research group reviewed data from the Vitamin D and Omega 3 Vital trial which included 2,000 men ages 50 and older and women 55 and older.

In her work, Dr. Costenbader looked at almost 17,000 participants who had blood tests for Vitamin D levels and Omega 3 fatty acids. The study groups were followed for over a five-year period. Those supplemented with Vitamin D and Omega 3 fatty acids reduced the incidence of autoimmune disease by 25- 30%.

Vitamin D supplements and Omega 3 Fatty Acid supplements are readily available, inexpensive and non- toxic when taken in appropriate dosages. Their use should be encouraged.

Prediabetes & Exercise

Prediabetes is a condition that identifies individuals who have an increased risk of becoming Type II diabetics. It is diagnosed with either a fasting blood glucose measurement of 100-125 or an elevated Hemoglobin A1C level. The Hemoglobin A1C level provides a look at the average blood sugar level over the previous 8-12 weeks and is fairly independent of the previous few meals.

Gone are the days of the physician saying to his patient, “your blood sugar was elevated at 120” and the patient responding, “Well it was my birthday this week and I had some cake and alcoholic drinks causing the elevation.” The hemoglobin A1C removes that reason.

When physicians diagnose patients with “prediabetes” we try and educate the patient and family encouraging dietary education on a healthy eating lifestyle, weight reduction if they are overweight and regular exercise. Fortunately, in the senior citizen age group, newly diagnosed prediabetics usually don’t end up developing full blown diabetes if they watch their weight and get active.

A recent study published in BMC Endocrine Disorders found that aerobic exercise was best at controlling Hemoglobin A1C levels but resistance training was not far behind. Those individuals who engaged in both aerobic training plus resistance training showed better weight control and fasting blood glucose levels than the control groups or aerobic training alone. When evaluating the data both aerobic training and resistance training helped. The message to me for my patients is, if you are a prediabetic, start exercising doing what you enjoy doing. Make it fun, not work. Couple that with a dietary education from a trained dietitian or diabetes peer educator and you will do well.

Zinc For Colds This Season?

Two weeks ago, my wife was doing her weekly childcare activity of love watching our two toddler grandchildren while our adult kids were on a business trip. The 3.5-year-old had brought home a viral respiratory infection the week before, gave it to his one-year-old brother and both kids were now in the tail stages of recovering from annoying but not serious illnesses.

In today’s world, coming home from school with a sore throat, runny nose and malaise means tea and honey, warm soup and a COVID-19 test. Both kids were negative but several days later my wife, then I, had similar symptoms. My wife’s symptoms settled in her sinuses and 10 days later her doctor put her on antibiotics and nasal spray. I was fortunately much less symptomatic but still have some nasal congestion and dry cough. We have a commercial preparation of a zinc product to prevent and reduce the symptoms of these infections but did not get around to taking them. In the past the literature wanted us to take these lozenges every two hours and I was not going to set an alarm at night to wake up to suck on a zinc tablet.

Jennifer-Hunter, PhD, from the Western Sydney University and associates studied the questions about zinc products’ effect on preventing and abating the common cold and published their findings in the online version of the BMJ Open on November 1, 2021. They looked at 28 randomized controlled studies with 5,456 patients. Their results showed that oral or intranasal zinc did prevent about 5 infections of those exposed per 100 persons when compared to a placebo. They found that if you challenged healthy individuals with a human rhinovirus inoculation the sublingual zinc did not prevent a clinical cold. Those who continued the zinc tended to have resolution of symptoms two days earlier than those who took placebo. For those who took the zinc prep there were more episodes of nausea and mouth and nose irritation.

I appreciate the science and think I will pass on the zinc for now and stick with avoidance of sick individuals plus chicken soup, tea and honey when I catch the virus anyway.

FDA Approves New Non-Verbal Computerized Test for Cognitive Impairment

Many of you are used to the Mini Mental Status Test or Montreal Cognitive Assessment Test during which an examiner asks you verbal questions and there are some pictures to interpret. This week the FDA approved a new test taken on an iPad or tablet using images of animals. The test asks you to classify the pictures as either an animal or nonanimal. The advantage of using the nonverbal picture test is it eliminates bias based on level of education and culture. In addition, it eliminates a successful score on subsequent tests due to a “learning the test” effect.

The test results can be incorporated into a patient’s electronic health medical record and become a part of the patient’s permanent chart. The test was given to 230 volunteers. There were eighty individuals with mild cognitive impairment, 55 with mild Alzheimer’s Disease and 95 healthy individuals. The results revealed the test was as sensitive as current verbal tests currently used to detect early dementia.

CognICA is the name of this new test and will be available for purchase in the next few months