Medical Bits – Vol. 3.5: Your Health and Medical News
At the outset of the pandemic, I developed an upper respiratory tract infection with rhinitis and severe congestion. I boarded a flight to Argentina to visit family. Upon arrival, I immediately recognized the distinctive features of tinnitus and mild associated hearing loss. My patients know how common and disturbing this problem can be. The prevalence of hearing loss doubles with every decade increase in age. Approximately half of persons reaching Medicare age and up to 80% of those older than 85 years of age have hearing loss sufficiently severe to impair communication.
Some of my patients indicate that progressive hearing loss is part of the “intelligent design” and adaptation to survive decades of marriage (for those in a relationship) and to limit the barrage of bad news and competing stimuli for our dwindling brainpower. Kidding aside, all recognize that untreated hearing loss damages communication affecting relationships with family, friends and co-workers. In addition, it may lead to a reduced quality of life, social isolation, and it is associated with higher rates of hospitalization, falls, depression, dementia and death.
Hearing loss is conductive (outer or middle ear), sensorineural (dysfunction in the cochlea or spiral ganglion), or mixed. Audiograms evaluate hearing thresholds across frequencies necessary for human communication.
The peripheral auditory system includes the outer ear, the middle ear, and the inner ear (cochlea), which contains the mechano-sensory hair cells that convert the mechanical energy of sounds into neural signals. These cochlear hair cells are innervated by spiral ganglion neurons, which in turn through the auditory nerve send their signals to the auditory nuclei of the brain stem.
The sensory hair cells are delicate and susceptible to damage from various stresses and do not regenerate. Hence, loss implies progressive acoustic impairment, which can also lead to degeneration of spiral ganglion neurons, complicating treatment with cochlear implants. Here is an excellent summary: review of Hearing Loss by Dr. Lisa Cunningham.
The degenerative effects of aging and the accumulated effects of “toxic noise”, toxic drugs and chemicals are the main causes of age- related hearing loss. It is usually bilateral, symmetric and most pronounced at higher frequencies > 2000 Hz with the consequent reduction in the ability to discern speech. Exposure to excessive noise and harmful sounds are ubiquitous in modern life. Think concerts, movie theaters, fitness classes, power sports, motorcycles, shooting, power tools. Numerous drugs are associated with cochlear damage: macrolide antibiotics (azithromycin); aminoglycosides (gentamicin family); cisplatin chemotherapy and derivatives. Smoking, obesity and diabetes also have strong association with additional hearing loss.
Sadly, today’s busy medical practice often does not permit enough time to explore and attempt to mitigate the social consequences of hearing loss.
Hereditary hearing loss among newborns affects 1:1000 births and there are over 100 genetic abnormalities and more than 500 syndromes with associated hearing compromise. It is not easy to separate genetic and environmental factors, but estimates of the heritability of adult-onset hearing loss range from 25-55%. The majority of single genetic defects compromise the normal functioning of the cochlea and those delicate sensory hair cells.
Most of you remember the progressive hearing loss and severe tinnitus that stroke Ludwig Van Beethoven in his late 20’s, leading to months of suicidal ideation and his final resolution to live for and through his art. Composition of his Misa Solemnis and Ninth Symphony required his prodigious musical memory and laying a stick over his piano which he would then bite to enhance the transmission of “sounds” and vibrations to his otosclerotic ears and damaged cochlear cells. He died at 56 of complications from cirrhosis and chronic pancreatitis and is buried in Vienna next to Frank Schubert.
Development of sudden hearing loss over less than 72 hours is a medical emergency and usually caused by viral, vascular or autoimmune injury that responds to immediate use of corticosteroids and occurs to about 4000-5000 fellow citizens annually.
Curiously, the USA is one of the few developed economies where there is no insurance assistance for hearing aids. President Biden issued an executive order this past Spring to expedite the availability of Over-The-Counter (OTC) hearing aids for mild to moderate hearing loss. But availability of the devices and discounting the price does not equate to usage as demonstrated by the Scandinavian experience, where it is a covered benefit and yet, the rate of use among the candidates is less than 15% in Finland but over 50% in Denmark.
- Use earmuffs or earplugs in noisy environments
- Limit time in loud venues
- Avoid ototoxic drugs
- Screen with audiologic testing if you (or family) notice declining acuity
- Use hearing aids if warranted
- For some, cochlear implants may be indicated and cost-effective
Fortunately, most of you have already been vaccinated and our region enjoys one of the highest vaccination rates of the nation. Some who have not been inoculated have been reluctant in part due to questions about safety and the novelty of the mRNA technology. Others, mostly West and South voice their “independence” or have made decisions based on unwise politization of this important public health issue. Some people have doubts because of “government meddling” and support of the vaccination programs. But let’s remember that the basic functions of government are to administer justice, enhance communication (roads, tracks, air-traffic, wires, wireless, etc), basic education and to regulate and provide public health. Vaccines were developed by private companies with financial public support. But science and only science have driven this very successful effort.
Due to that lower vaccination rates of Southern and some Mid-West States, Critical Care-trained physicians have been asked to work away from home. Many ICU’s are now full, with shortages beds, nurses and trained physicians. Even oxygen is in short supply.
In my personal experience working at several hospitals in and around Atlanta, out of over 100 patients with COVID-19 associated pneumonitis and respiratory failure seen over the course of two separate weekends, only one patient had been fully vaccinated in December of 2020 and had uncontrolled diabetes and obesity (known risk factors for severe disease).
More than 4 billion vaccines have now been deployed worldwide and several new studies are able to put into context some of the few adverse effects from vaccination for physicians and their patients to make better informed decisions for those few “hold-outs” and may also help parents trying to decide if their adolescent children should be vaccinated or if those younger than 12 should be immunized once the vaccine approved for children, later this fall.
This past week, a study involving the largest Israeli healthcare system published their observations, demonstrating that the excess risk for each one of the reported significant adverse events in this population of 1.7 million individuals, was many folds higher from infection with SARS-CoV2 than from vaccination.
The only exception was a minimal increased risk of Herpes Zoster (shingles) (but you should all be vaccinated with the two-shots of recombinant Shingrix Vaccine) and development of lymphadenopathy. This is not unexpected, as we want vaccination to trigger an immunologic response and activation of lymph nodes and their lymphocytic foci to foster adequate immunologic protection.
Some of you remain concerned about other rare complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) which have now been reported to European and US agencies. Fortunately, VITT are rare occurrences (approximately 1 case per ½ million doses) more common in young women, several on BCP or hormone replacement therapy (but a firm link has not been established) and we now know how to recognize them and effective treatment is available! These are very rare complications and pale in comparison to the benefits of preventing COVID-19 which has a mortality of 0.2-2% (depending on host) and potential long-term damage as discussed over the past few months.
Several new studies report on the efficacy of vaccines and the minimal decline in efficacy with the new Delta variant.
In a case-control study of almost 11,500 fully vaccinated Israeli health care workers (Pfizer-BioNTech), 1500 of them, were exposed to infected individuals or became symptomatic. There were 39 breakthrough cases and in this mostly young (mean age 45) group, all were mild or asymptomatic but the delta variant accounted for only 15% of cases in the study period.
Another study published on August 12th demonstrated a modest decline in efficacy against the Delta Variant of 5-6%
but remained highly effective to prevent hospitalization and severe disease.
At this time, there are twelve vaccines against COVID-19 approved in different nations and 32 vaccines making progress at the final Phase III clinical trials. In the US, the Pfizer – BioNTech received definitive FDA approval on August 23rd, 2021 and the two others are anticipated to be fully approved within the next few weeks. The two mRNA vaccines were deployed in December 2020 after the Pfizer – BioNTech and Moderna – NIH-NIAID received preliminary approval and EUA and full approval in some nations. These vaccines had an impressive 95% efficacy and safety, as reported in their phase IIB-III clinical trials. Both require two injections, but early protection was noted as early as 12 days after the first injection. In the period between injections, the efficacy was almost 75% and the likelihood of severe disease declined even further. On February 27th, the Johnson & Johnson modified adenovirus vaccine received EUA. The Novavax vaccine announced results of phase III clinical trial of its NVX- CoV2373 Vaccine in late June 2021, with 90.4% overall efficacy and 93% efficacy against the five most prevalent SARS-CoV2 variants of concern. Approval is anticipated later this summer. The Gaithersburg company will supply up to 1.1 Billion doses to the international Vaccine Alliance – GAVI, supported by the WHO, the Bill and Melinda Gates Foundation, UNICEF and The Worldbank Group.
COVID-19 Variants and Mutants
There are several open-source databases tracking SARS-CoV-2 genomic sequences, but the largest and most popular is GISAID.
It was originally conceived in 2006 as a “bank” of genomic data from flu viruses, but the Pandemic has expanded its mission to promote the rapid sharing of data from all influenza and coronaviruses to help researchers understand how viruses evolve and spread during epidemics and pandemics. Scientists are able to upload the genomic sequence of the viral strain present in their communities. Their hard work has led to the sharing of more than 1.5 million coronavirus genome sequences from 172 nations, allowing researchers to track the development and movement of new variants across the planet.
Nextstrain, is another open-source consortium that follows numerous infectious diseases and updated several times weekly, tracking the global spread and flow of variants. You can read and explore more here.
How effective are vaccines against the variants reported? The vaccines remain EXTREMELY EFFECTIVE and all appear to make serious disease rare!
Some of you worry about the new variants and the potential for decreasing efficacy of vaccination, a fear that is exacerbated by the News. We should remember that despite the higher transmissibility of the Delta Variant, immunization makes serious disease rare! And another reason to be sure you are all properly immunized. Since some of these new variants require higher antibody titers to achieve neutralization and those titers decline over time, boosters may become necessary after several months as you have already learned over the past few weeks.
There are some exceptional situations where immunocompromised hosts need booster immunization much earlier. That includes patients receiving active chemotherapy for malignant conditions, those with history of lymphoma, leukemia, prior organ transplantation, multiple myeloma or active immunosuppression for treatment of vasculitis, connective tissue diseases or autoimmune conditions. Most people do not fall into this category and can safely wait for their booster shot later this fall and winter.
A recent study outlined the particular risk posed by immunocompromised hosts, who are at risk for prolonged Covid-19 infection. That inability to clear the infection may give rise to multi-mutational SARS-CoV2 variants. The report highlighted the presence of multiple variants of concerns in these vulnerable hosts, suggesting that viral evolution in immunocompromised patients may be an important factor in the emergence of such variants.
We have discussed in the past how SARS-CoV-2 relies on its Spike protein to attach to the epithelial cells of the respiratory system and become internalized into those cells to hi-jack the metabolic machinery to replicate and cause disease. Vaccine development has focused on this protein and all of them inoculate conformational variants of the Spike protein (mRNA particles encoding for them – proteins – attenuated viruses that expose the same antigen protein and inactivated viruses).
The P.1 and B.1.351 mutants, share a mutation that leads to a conformational change in the Spike protein and thus, appear to make the vaccines less effective, requiring higher neutralizing antibodies titers (NAb).
The variant B.1.617 (so called, Delta variant) initially detected in India in late 2020 has “dual” mutations –E484Q and L452R – likely responsible for their severe epidemic this past Spring, as they increase transmission, severity of illness and reduce the neutralization power achieved with vaccinations. We should emphasize that the immunogenic response and titers of antibodies induced by vaccination are highly effective and responsible for a 5-fold decrease in the risk of mild disease and a 29-fold decrease in the risk of hospitalization.
As discussed in the past, science is keeping up with these mutants and the timing of boosters will be announced within a few weeks. For an excellent review of New Variants and Mutations.
A summary from the NEJM follows in this table.
This NYT link has National and International Vaccine Rollout information.
WHY WOULD HUMANS DECLINE VACCINATION?
We must invite those hesitant about vaccination to share their fears, concerns and reasons to avoid vaccination. Here you can find an excellent review about vaccine hesitancy. Open ended questions such as “What do you think about the Covid vaccine?” may provide an opening to discuss and allay concerns. Here is a wonderful interactive feature to help you and those slow to embrace the protective potential of vaccines.
Multiple surveys throughout our Nation have been completed and we now have maps that analyze the different reasons delaying vaccination. The most common:
- 14% of the US population are “COVID Skeptics”.
- 9% are “Cost-Conscious” and can’t afford to take time off or be out of work due to potential side-effects from the vaccine.
- 8% are “Watchful” and waiting to see how safe and effective vaccines really are.
- 4% are “Healthcare system Distrusters” and distrusters of the government in general. Fear of vaccine side-effects or complications is the most quoted.
WHAT TO DO?
- “COVID Skeptics” – Most common in AS, ND, NV- Avoid antagonizing or discrediting their beliefs. Best to acknowledge their thoughts and feelings and provide facts, underlining that vaccination not only protect them, but will protect their families and friends.
- “Cost-Conscious” – Most common in MS, WV, TN, AL and states with high poverty rates. In these places bringing the vaccine “to the people” and into churches, schools, grocery stores, will increase vaccination rates.
- “Watchful” – Most common in DL, HI, RI, OK, WV and WY. People are waiting to see how friends and acquaintances perform after vaccination. For them, best to keep the option of vaccination open and use gentle persuasion and data to nudge them in the “right” direction.
- “Healthcare system Distrusters” – Most common in DC, MD, GA and particularly among African-American and Hispanic minorities. Here it is important for the public health authorities to partner with trusted members of the communities, provide equitable access to vaccination and to have transparent communication to enhance acceptance.
COVID-19 Vaccines: Q & A
1. Do we need vaccine mandates?
In my opinion, YES. We have vaccines that are highly effective, safe and fully authorized. For humans who want to continue to participate in social functions, such as public venues, concerts, sporting events, restaurants, schools or work-places, vaccination should be required. Even if we are immunocompetent and do not fear poor outcomes, it is our personal and social responsibility to assist with the creation of an immunologic wall to prevent disease transmission and the rise of new variants.
2. Is Pregnancy a contraindication to Covid-19 vaccination?
No. In fact, a recent study confirmed no safety concerns with the mRNA vaccines and adequate protection.
The safest or most rational timing of vaccination during pregnancy has not been established, but as indicated in our prior “Bits”, best to inoculate in the second trimester, to ascertain protection to the mother in the third trimester (when infectious complications are more common) and to facilitate the placental transfer of antibodies and protection to the newborn.
3. Do we need to continue to decontaminate surfaces?
No. As we learn more about transmission, we know that this is an airborne disease. It is highly unlikely that we can pick up an “infectious dose” on our fingertips.
4. How long patients continue to shed live viruses?
The median time from symptom onset to viral clearance in culture was 7 days (+/- 5 days) but the median time to clearance of PCR was 34 days. The latest positive viral culture was 12 days after symptom onset. Thus, we may continue to shed the viral particles for a while, but they may be inactive and not likely to cause disease. This period may be significantly longer in immunocompromised patients.
5. Do I need to have oxygen available in case of need?
No. There is no evidence that more oxygen is better. In fact, multiple studies have shown that only patients with persistent oxygen saturation below 89% benefit from Oxygen. This applies to all humans, including patients with COPD, emphysema, heart failure and the rest. Most people discharged home on oxygen, do not need supplemental oxygen upon re-testing 2-3 weeks later. If you are “hoarding” an oxygen concentrator, have your physician return it and use those precious healthcare funds for other beneficial treatments.
6. Are the vaccines safe?
YES. All the vaccines approved in the US are safe, trigger an excellent immunologic response across all age groups, are highly protective and cause minimal injection-site reactions and fatigue/malaise and occasional headaches (symptoms that are generally attributable to all vaccines and due to the immunogenic response triggered by the introduced antigens). The incidence of anaphylactic reactions (mostly in those with polyethylene glycol intolerance) is below 5/million inoculations and develops within 20 minutes of administration and Vaccine-associated clotting (VITT) complications reported above occur to about 1:500,000 people and we now know how to recognize them and treat effectively. Other abnormal immune responses such as persistent body aches, pericarditis, pleuritis, myocarditis and muscle aches have been reported as indicated above, but the incidence is much lower than that caused by active infection with SARS- CoV2
7. What is the duration of the protection elicited by vaccines?
The protection is anticipated to last at least 6-12 months and possibly longer as the cellular immunity is stimulated as well and it is a long-lasting defense.
8. Can vaccines possibly aggravate pre-existing conditions?
Yes. There are few reports of flares of autoimmune and inflammatory conditions such as inflammatory bowel disease, Crohn’s ulcerative colitis and polymyalgia rheumatica reported. But the benefits of vaccination outweigh the risks by many folds.
9. Could the messenger RNA vaccines get integrated into my DNA and cause mutations or long-lasting ill-effects?
No. This is biologically impossible. The small messenger RNA is quickly broken down and does not interact with humans’ DNA. Both vaccines have a tiny segment of mRNA encased in lipids.
10. Asymptomatic individuals do not transmit COVID-19.
They do. Multiple studies indicate that nearly ½ of transmissions are from people not feeling ill and about a third of all infected patients remain asymptomatic.
11. Is the virus mutating such that the efficacy of vaccines is in peril? DO NOT WORRY!
Of course, the virus is mutating, just like any other virus multiplying in the trillions and infecting millions of hosts. As discussed, some of the mutations may lead to increased infectivity and severity of disease. SARS-CoV2 is a stable, non-segmented RNA virus. The infectivity of the virus increased early, as a result of a specific mutation carrying the spike protein D614G substitution, augmenting the virus infectivity and becoming the dominant strain causing disease in Northern Italy and the most prevalent variant throughout the world for most of 2020. New variants with heightened infectivity such as B.1.1.7 and now B.1.617 (so called, Delta variant) are displacing other less “efficient” strains. But vaccines remain effective and you will be ready for a booster vaccine “update” later this fall, when recommended.
12. Should people who recovered from COVID-19 be vaccinated?
Yes. It is not certain how long the immunity will last, and although long term humoral and cellular immunities are anticipated, the recommendation is to be vaccinated 90 days after the acute infection (mine: do it earlier!)
13. Are people who cough or sneeze more infectious than others?
No. Transmission appears to be driven by the viral load of index cases. A higher viral load also increases the risk of developing symptomatic disease shortens the incubation period in a “dose-dependent” manner, as reported by The Lancet.
14. When will vaccines become available for Children?
The clinical trials that led to the approval of the mRNA vaccines included adolescents ages 12-17. As of now, everyone older than 12 can be vaccinated. Children ages 6 months to11 years may have to wait till early fall as the results of the trials initiated in early March 2021 become available.
You have all heard of multiple new treatments or re-purposed treatments against Covid-19 related disease.
It is important to emphasize what is effective and what has been proven to be worthless.
While working in ICU, I have witnessed expensive and potentially deleterious and invasive treatments being imposed sometimes by physicians and more frequently demanded by family members, despite the lack of evidence for benefit or other times possible harm. The Hippocratic oath reminds us: “Primum non Nocere”!
The National Institutes of Health has a wonderful resource available to all which summarizes the evidence in their NIH Covid-Treatment Guidelines, which grows steadily and now stands at over 350 pages. In summary:
- Use Dexamethasone at 6 mg daily for 10 days after diagnosis of COVID-related pneumonitis.
- In hospitalized patients, use IV Tocilizumab.
- If Tocilizumab not available use Sarilumab IV
- Use Casirivimab plus imdevimab SQ or IV for post-exposure prophylaxis in patients at high risk for progression to severe Covid- 19 and unvaccinated.
- May use Sotrovimab in similar settings.
- Azithromycin and Ceftriaxone have no benefit
- Immune convalescent plasma from previously infected patients: marginal benefit
- Plasma exchange – plasmapheresis. No benefit, costly and invasive.
- Colchicine. Insufficient evidence. Do not use
- Interleukin 1 – 6 inhibitors. Insufficient evidence. Do not use.
- Ivermectin. Insufficient evidence. Do not use.
- Janus Kinase Inhibitor Baricitinib. Promising. Use in the right setting.
- Anticoagulants. Only in prophylactic doses.
For core strength, try this 9-minute routine!
Let’s all remember that the only certainty in life, is death and the only fountain of youth proven by science and experience are exercise, laughter, humor and a positive attitude!
- We will no longer see unvaccinated patients at the office (unless special attenuating circumstances exist). We have been working to keep our patients safe for many months, and at this point with the final and complete approval of effective vaccinations, we feel it is imperative to provide a safe environment for our patients.
- Simran Singh, Samantha Morales, Sarah Molinari and Fiona MacNair are our current Medical Assistants and will continue to assist all of you with your healthcare need. Simran Singh at firstname.lastname@example.org is my personal assistant.
Wishing you a happy and healthy fall!
Carlos E. Picone, MD
5215 Loughboro Rd NW, Suite 400
Washington, DC 20016