Medical Bits – Vol. 3.1: Your Health and Medical News

Vaccine Update

SARS-CoV2 Vaccine Deployment – “The Magic Has Started”

Many of you wonder about the efficacy of the different vaccines and want to know which one they should get The answer: whichever comes your way! Roll up your sleeves and get the jab! And to keep up with developments you might want to listen to this podcast!

At this time, there are nine vaccines against COVID-19 that have been approved in different nations. There are many more in the “pipe- line”. In the US, only two mRNA vaccines have been deployed so far: the Pfizer – BioNTech and the Moderna – NIH-NIAID received preliminary approval and Emergency Use Authorization (EUA) in December, 2020. Both vaccines had an impressive 95% efficacy reported in their phase IIB-III clinical trials and 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 60% and the likelihood of severe disease declined even further. This impressive protection was achieved with excellent safety.

Considering these encouraging immunogenic responses (ability to trigger an immune response) and effectiveness, most of you are probably scrutinizing the news for evidence of protective results from the (bumpy) immunization campaign! Of course, we must reach high vaccination rates in order to see those results. After a slow start, we are not likely to be near the levels of vaccine penetration in our community until the Spring.

Israel has been the nation with the highest share of their population vaccinated. By February 1st, the number of hospitalizations among those over-60’s dropped precipitously! Three weeks before, 70% of them had already been vaccinated. As reported by The Economist, on February 1st, researchers from around the world read the tweet: “We say with caution, the magic has started.” Eran Segal from the Weizmann Institute of Israel had been posting updates about the Israeli COVID-19 experience. By February 6th, 85% of the over-60’s and 40% of the general population had received at least one dose of the mRNA Pfizer vaccine (and a few Moderna’s).

As you can see in this graphic from The Economist, hospitalizations in the cohorts with high vaccination rates, is plummeting!

Despite this exciting news, we all read with a bit of concern the rise of new mutants of the virus which make it more contagious. As discussed in prior “Bits”, this is not unexpected, as viruses replicate trillions of times in each host, leading to multiple opportunities for genetic alterations and mutations. Of course, the most infectious eventually get the upper hand, as they are more effectively transmitted between unsuspecting humans. Thus, the B.1.1.7 and the B.1.351 variants are now spreading far and wide. Another P.1 mutant is also spreading.

Despite the drum-beat of worrisome news about novel strains of the virus, we should remain optimistic! The vaccines all appear to make serious disease rare! While disease may still occur in some instances, particularly with the P.1 and B.1.351 variants, disease leading to hospitalizations in vaccinated individuals appears to be uncommon. And data from the clinical trials indicates that infectivity is decreased by more than 50%. Information from Israel suggests that in the few that develop infection after vaccination, the viral load is much lower, making them less infectious.

The SARS-CoV-2 virus relies on its Spike protein to attach to the epithelial cell of the respiratory system to infect the individual and become internalized into those cells to hi-jack the metabolic machinery to replicate. Vaccine development has focused on this protein and all of them inoculate conformational variants of the Spike protein via different means (mRNA particles encoding for them – proteins – attenuated viruses that expose the same antigen protein and inactivated viruses).

We have discussed the different types of vaccines in the past. 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 a bit less effective. But the good news is that science and technology are keeping up with the “bad guys”. Vaccine makers are already tweaking the vaccine and a few are developing “multivalent” vaccines for full protection against different strains. It is also possible that since COVID-19 is here to stay, we may need a booster vaccine to cover new variants in the future. In fact, Britain’s National Health Service, which is planning to vaccinate all “willing” adults by the end of the summer, is planning to deploy a “booster” shot to cover new variants by the fall. Seven new variants were reported today in the US and will continue to become more prevalent.

Here you will find an excellent review of New Variants and Mutations.

Judging from the questions I have received from my patients, many remain concerned about the safety of these messenger-RNA vaccines. Let me emphasize: They are extremely safe!!! Anaphylaxis was reported at 5 and 2.8 events per million doses for the BNT162b2 (Pfizer-Bio-N-Tech) and mRNA-1273 (Moderna – NIAID) vaccines respectively. The vast majority occurred within 30 minutes and in people with a history of allergic reactions. The mechanism appears to involve an IgE mediated reaction and sensitivity to polyethylene glycol may be responsible. If you have a prior history of polyethylene glycol intolerance, you may have to wait for one of the other vaccines such as the Johnson and Johnson or the Novavax vaccines which should be approved later this month.

These vaccines can be stored in regular refrigerators and the Adenovirus- based Johnson & Johnson requires only one shot!

We should pause and remember that not only the vaccine was developed in 10 months, but also new technology was engineered to manufacture antigen and deliver this important achievement!

As indicated on prior “Bits”, vaccines against viruses historically used “attenuated” or debilitated strains of the virus so as to coax the body to build defenses but not cause disease. The novel vaccine development has used genetic engineering, targeting the gene for the distinctive Spike protein that studs the virus’ membrane hoping it would provoke a brisk immunogenic response. Other joint ventures used the spike gene, inserting it into the genome of a harmless adenovirus which after infecting human cells it too, makes them produce spike proteins that trigger an immune reaction.

The frequently updated Coronavirus Vaccine Tracker from the NYT is an excellent resource. As mentioned, there are now 9 vaccines approved in different nations, 20 have reached the final stages of clinical trials and researchers continue to test 69 vaccines. Another excellent Covid-19 Research update from Nature.

Vaccine allocation

When is it my turn to get this long-awaited vaccine?

As previously discussed, the vaccine is being deployed in stages. In mid- September, the World Health Organization and the US National Academy of Sciences, Engineering and Medicine proposed a five-phase plan to fairly allocate a coronavirus vaccine internationally and to US residents respectively. I invite you to read more about it here.

In summary, the allocation of vaccines will attempt to maximize benefits by inoculating first responders and those most likely to become severely ill first. I invite you to read more here.

For specific deployment plans review your state: Maryland – for vaccine registration.

District of Columbia – for vaccine registration or call 855-363-0333.

Virginia – a new comprehensive website will be available later this week for Virginia residents. For now, best to go to your county’s website.

The good news is that vaccine distribution nationwide is accelerating and is now up to 1.7 million doses daily (and above the target of 1.5 million doses set by this administration).

This NYT link has National and International Vaccine Rollout information.

MASSIVE VACCINATION PROGRAMME

As discussed in December, the logistical difficulties of fair administration of a “shot” to all members of our race are daunting. In addition, we will have to contend with unfounded fears, irrational beliefs, dogmas and disinformation populating online and printed media.

This vaccination effort, is essential to protect Humanity and will include every imaginable manner to penetrate society and ascertain adequate uptake to reach at least a 50-60% uptake, considered necessary to obtain “herd-immunity” and it is already under way. Despite a slower than desired distribution, we remain confident that the pace will pick up considerably once additional vaccines become available.

Vaccines have been shipped to hospitals, pharmacies, stationary and mobile teams deployed by public health authorities and even large stadiums for mass-administration.

We have applied to both, DC and Maryland’s Health Departments to procure shipments of vaccines for our patients and will keep you all apprised. But so far, as reported by the NYT, private physicians and your Primary Care Doctor are frustrated by the process and feel somewhat marginalized. But we remain confident that as more vaccines become available and supply starts to become more balanced with demand, things will change. We certainly want to be part of the solution and help on the quest to vaccinate Humanity.

Anti-VAXXERS?

As reported by Nature, The Economist and other publications, the worldwide acceptance of vaccination appears to be no more than 55-70%. It is remarkable that billions of people would expose themselves to the ill- consequences of disease without the immunologic protection afforded by a simple “shot” or two.

But this is not a new phenomenon. In the late 1790’s when Dr. Edward Jenner began vaccinating people with cowpox to prevent smallpox (a disease that carried a 10% mortality and eradicated from the planet in 1977 through vaccination), there were immediate pockets of resistance. Others, such as Napoleon, embraced vaccination at once, jabbing all of his soldiers and considered Jenner “one of the most faithful servants” in his endless European wars.

The acceptance of vaccines appears to be “fluid” and imprecise, but as described in detail by The Economist, there are many members of our species with doubts. We must all work to allay those concerns and promote enhanced penetration of the one modern advance that has decreased morbidity and mortality, extending human life.

Surprisingly, some of our health-care co-workers had concerns about unknown risks, side-effects and the regulatory approval process. The work to answer any and all concerns and to eliminate disinformation from social media continues.

The Centre for Countering Digital Hate (yes, there is such a not-for-profit group!) tracks more than 400 anti-vaccine accounts on Facebook, Instagram, Twitter and YouTube that actively spread COVID-19 misinformation. They have almost 60 million followers! Last week, Facebook agreed to silence the most egregious offenders. It may be too little and too late…

HAIR: ARE YOU LOSING IT?

I don’t know about you, but after a year of incessant news and reports about SARS-CoV-2 and COVID-19, I feel we should be addressing other issues a bit “lighter”. And what’s the lightest part of our body and getting constantly “lighter”? HAIR.

We have on average 100,000 hair follicles on our scalp and they have four phases of growth. They are all on different stages and have no more than 20 growth cycles. Yes… We have a finite amount of hair growth in our lifetime!

Anagen: Growth, lasts between 2 and up to 6 years and 85-90% of hairs are in this stage.

Catagen: Transition, 10 days. <1% in this stage Telogen: Resting, 100 days. 10-15% in this stage Exogen: Shedding.

Hair grows about 1 cm per month and about 150 hairs are shed in a normal “exogen” phase. This is more than we suspect.

Genetic factors are important and the influence may come from both, maternal or paternal side. Some conditions may cause “scarring” and they should be evaluated by your dermatologist. Non-scarring alopecia is what most humans encounter, sooner or later: More than 80% of men and 50% of women show evidence of androgenic alopecia by age 70.

Topical minoxidil can prolong the anagen (growing) phase and enlarge the hair shaft. Stopping the medication may precipitate hair loss and sometimes is associated with a paradoxical worsening of hair loss for the first 4-6 wks. Other medications that may help include finasteride, dutasteride and spironolactone. Most OTC products will thin out your pockets with little hair to show for it.

DEBUNKING MYTHS: Q & A

1. Are some vaccines better than others?

We do not know the answer to this question, as no comparative studies have been completed and they are not likely to be undertaken soon. It is very difficult to compare clinical trials, as all have different parameters, antigen dosing, interval between injections and population studied. It appears both messenger RNA vaccines have similar efficacy. The attenuated adenoviruses vaccines may be ready by January 2021 and it will be most interesting to see those results. We should prepare to accept any vaccine that comes our way!

2. Are the vaccines safe? Can they possibly aggravate pre- existing conditions? What is the duration of protection?

These are all important questions and the answers are ongoing. The only clinical trial available for full review demonstrated that the vaccine triggered an excellent immunologic response across all age groups, was highly protective and caused 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 protection is anticipated to last at least 6-12 months and possibly longer as the cellular immunity is long-lasting and appears to be triggered as well. As reported above, the incidence of anaphylactic reactions (mostly in those with polyethylene glycol intolerance) is below 5/million inoculations and develops within 20 minutes of administration.

3.  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.

4. Are all Coronavirus tests the same?

No. One is the virus test, to learn if you are actively infected and the other is the antibody test to learn if you have been infected in the past and have immunity. The most accurate virus test is the Polymerase Chain Reaction – PCR which identifies the gene of the virus in nasopharyngeal secretions or saliva. It is more accurate but more expensive and labor intensive. Rapid tests identify specific viral antigen or coronavirus proteins implying active infection. They are less accurate but faster and cheaper.

A new Home Test developed by an Australian company was approved in December.

Some of our patients ask if we offer the antigen tests: NO. Due to concern for increasing traffic and bringing in individuals who could possibly carry the virus and expose other patients, we decided not to offer testing.

5. Where can I be tested?

Locally, there are several sites (Sibley Hospital – 202-537-4190 but best to have an order from your doctor sent in advance; Kelly Goodman, NP offers testing through Capital Dx – 202-684-7167; AllCare Family Medicine 301-825-8880 in Glen Echo; ARCpoint labs in Spring Valley 202-880-3389 and MedStar Urgent Care in Chevy Chase 301-215-9440. You must call for an appointment in advance. There are now mail-options: CareCube and Pixel by LabCorp, will mail a test and you send back a sample; they promise to send your results within 12 to 34 hours and 36 hours respectively.

6.  Asymptomatic individuals do not transmit COVID-19. Myth! Multiple studies indicate that nearly ½ of transmissions are from people not feeling ill and about a third of all infected patients remain asymptomatic.

7. Do antibodies last and could I get re-infected with COVID-19? The fact that after more than 8 million cases worldwide only one case was confirmed to have developed reinfection by the summer of 2020, indicates that this is a very rare phenomenon. In late August, a 33-year-old Hong Kong resident, who had his initial infection in the early Spring, tested positive again upon return from Spain via the UK. He remained asymptomatic and mounted a vigorous antibody response to the second strain, confirmed by genetic analysis. Antibodies last several months and our cellular immunity takes over after antibody titers

Antibody titers appear to remain elevated for 4-5 months after infection and then they start to decline. Gleaning information from the SARS-CoV1 epidemic of 2002, adequate titers of neutralizing antibodies remained elevated 2-3 years after acute infection.

8. COVID-19 is associated with increased risk of clotting and therefore we should take aspirin or blood thinners. No. Patients who develop severe COVID-19 disease and usually those requiring ICU support, may go on to develop small clots and disseminated intravascular coagulation. For those patients, anticoagulation treatment may be warranted and is decided by the ICU team at the time of care. Use of preventive blood thinners is unfounded!

9. Is the virus mutating to be able to be infectious through the skin? No! There is no evidence that this is The virus utilizes special receptors located in the respiratory epithelium called ACE-2 (Angiotensin Converting Enzyme type II) to be internalized and infect epithelial cells. Furthermore, the probability of becoming infected from packages and surfaces is extremely low. Stop wasting time and disinfecting surfaces and packages. Not likely to get to your upper airway in an adequate infectious dose. Additionally, it seems that smokers and asthmatics have a lower incidence of COVID-19 related disease, probably due to mild airway inflammation that may decrease the density of those ACE-2 receptors in the respiratory epithelium and possibly decreasing the internalization of virus into the respiratory mucosa, necessary step for development of disease.

10. Is the virus mutating such that development of an effective vaccine is in peril? 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 but more “aggressive” behavior and potential to cause worse disease has not been seen. SARS-CoV2 is a stable, non- segmented RNA virus. Yet, the infectivity of the virus appeared to have increased early on in the pandemic 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. Now, new variants with heightened infectivity are at work such as 1.1.7 which are displacing other less “efficient” strains.

11. UV light / silver and copper-based agents destroy SARS-CoV2 and are effective preventive or treatment modes. Myth!

While prolonged UV light may inactivate the virus, using UV light has no immediate effects and is potentially harmful. Metal-based products have no known effect on the virus

12. Do masks help decrease the severity of illness and could they diminish Influenza transmission? Likely YES! There appears to be a relationship between the infectious dose and severity of The rate of asymptomatic infection was estimated at 40% by the CDC in mid-July, but they have been reported to be > 80% with universal masking. In a closed Argentinian cruise ship outbreak, where all passengers and staff were provided with masks, the rate of asymptomatic infection was 81% (compared to 20% in earlier ship outbreaks).

13. Should people who recovered from COVID-19 infection 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.

14. 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.

What can we do to prevent infection and disease?

Keep cool, do not panic, eat a nutritious and diverse diet, stay active and be happy!

AND EXERCISE!!!

If you have 7 minutes daily, you can start to improve your fitness right now, and 11 more minutes will get you in shape!

Use a properly fitted mask while in public indoor places.

Take a multivitamin daily and don’t forget your 1000-2000 IU of vitamin D3. Possibly Zinc 11mg supplements. Ivermectin, Hydroxychloroquine and Azithromycin have all been debunked.

Be ready to accept the JAB as soon as possible!

And let’s continue to make the best lemonade with the “lemons” nature has thrown our way!

Fear is not a rational response. This too shall pass! Do not anguish about rare problems unless you have won the lottery more than once.

Remember that the only certainty in life is… death… and the only fountain of youth proven by science, experience and millennia are exercise, laughter, humor and a good positive attitude!

Let’s try to concentrate on better times ahead and continue to enjoy every minute of this most interesting JOURNEY and continue to cherish your family time!!!

 Carlos E. Picone, MD

5215 Loughboro Rd NW, Suite 400

Washington, DC 20016

301-656-7374

cpicone@chevychasepulmonary.com

References:

https://www.nejm.org/coronavirus https://www.cdc.gov/coronavirus/2019-nCoV/index.html

https://www.who.int

https://clinicaltrials.gov/

https://www.nature.com/articles/d41586-020-00154-w]

https://science.sciencemag.org/content/early/2020/05/12/science.abc5312 https://www.nejm.org/doi/full/10.1056/NEJMp2005630?query=featured_coronavirus https://www.youtube.com/watch?v=-Gn8oJY1VHY&feature=youtu.be https://www.cfr.org/backgrounder/what-world-doing-create-covid-19-vaccine https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805090/ https://www.nejm.org/doi/full/10.1056/NEJMcibr2009737?query=featured_coronavirus https://jamanetwork.com/journals/jama/fullarticle/2767840

https://www.nature.com/articles/d41586-020-00502-w

https://www.nap.edu/catalog/25914/discussion-draft-of-the-preliminary-framework-for-equitable-allocation-of- covid-19-vaccine

https://www.economist.com/briefing/2020/11/14/an-effective-covid-19-vaccine-is-a-turning-point-in-the- pandemic

https://www.economist.com/briefing/2021/02/13/vaccine-hesitancy-is-putting-progress-against-covid-19-at-risk https://www.nature.com/articles/d41586-020-00502-w

ANNEX: COVID-19 Timeline

From Nature:

• 21 December, 2019, a few patients became ill with severe pneumonia in Wuhan, Hubei province of
• 31 December, 2019, a new virus is identified in samples from 4 patients with pneumonia of unknown cause. All patients had been present at the Huanan Seafood Market in Wuhan. Viral genome isolated and sequenced. Initially named 2019-NCoV (Novel Coronavirus 2019).
• 8 January, 2020 – Nature reports on the new virus, cause of mysterious “deadly pneumonia” in Wuhan,
• 21 January, 2020 – First US case confirmed in Washington State. 30 yo man returning from Wuhan,
• 23 January, 2020 – China closes
• 24 January, 2020 – Second US case. 60 yo woman returning to Chicago after visiting
• 28 January, 2020 – Human-to-human transmission confirmed in Germany.
• 3 February, 2020 – Study of live virus
• 6 February, 2020 – Retrospective autopsies completed in mid-April in Santa Clara, CA confirms that first deaths occurred in early
• 14 February, 2020 – Chinese authorities reveal number of infections in medical staff: 1,716 health workers had contracted the virus, 6 of whom died
• 17 February, 2020 – First case in Africa
• 25 February, 2020 – S. emergency funding for coronavirus response
• 26 February, 2020 – Brazil reports first case in South America
• 28 February, 2020 – Coronavirus spreads to sub-Saharan Africa
• 4 March, 2020 – Multiple drugs under investigation for coronavirus
• 5 March, 2020 – China study suggests children are as likely to be infected as adults, but most do not become
• 11 March, 2020 – Transgenic animals for CV research in high demand
• 11 March, 2020 – Coronavirus becomes a pandemic, says
• 13 March, 2020 – US President declares “national emergency”. It is no longer a “Chinese virus that will blow over by the spring”.
• 17 March, 2020 – First vaccine clinical trials begin in U.S. (National Institute of Allergy and Infectious Diseases (NIAID) and Moderna (biotechnology company in Cambridge, MA) – “launched in record speed,” 66 days from genetic sequencing of virus to the first human injection of the vaccine
• 18 March, 2020 – Deaths in Italy surpass those in
• 19 March, 2020 – No new cases confirmed in Hubei,
• 25 March, 2020 – Retrospective studies in Lombardy confirm that the virus was present in Northern Italy in early January
• 1 April, 2020 – Over 80% of ICU patients with COVID-19 have underlying medical
• 2 April, 2020 – Worldwide cases surpass 1,000,000.
• 7 April, 2020 – No new reported COVID-19 deaths in China
• 8 April, 2020 – Tracking App reveals lack of smell is key
• 15 April, 2020 – Trump – in his infinite wisdom and trust-worthy scientific knowledge – suspends WHO funding. Leonardo Da Vinci’s birthday celebrated by “scapegoating” the
• 15 April, 2020 – Worldwide infections surpass 2,000,000.
• 21 April, 2020 – Mars probe HOPE ships from UAE to Japan for launch after July 15th when Mars and Earth are aligned. It should reach the Red Planet by
• 21 April, 2020 – https://1daysooner.org/volunteer 15,000 people volunteer to be exposed to virus and accelerate vaccine development.
• 27 April, 2020 – The five ways Trump is undermining environmental protection under the cover of the Pandemic: https://www.nature.com/articles/d41586-020-01261-4
• 29 April, 2020 – Remdesivir speeds up recovery!
• 7 May, 2020 – First CRISPR testing kit approved in US. It works by programming the CRISPR machinery to detect snippets of the virus genetic material and expedites results to 1
• 15 July, 2020 – Only medications with proven efficacy so far: Remdesivir (antiviral) and dexamethasone, when used in patients with pneumonitis seems to expedite recovery, but not early on. In fact, it may worsen outcomes when used at the outset of disease. Non- Invasive oxygen delivery may be associated with better
• 16 July, 2020 – mRNA vaccine able to generate adequate immunogenic responses and phase III clinical trial to begin
• 20 July, 2020 – Recombinant Adenovirus vaccine that encodes SARS- CoV2 Spike protein is highly immunogenic on phase I/II clinical trials conducted in the UK and phase III trials to start
• 27 September, 2020 – Over 33,000,000 cases and almost 1,000,000 deaths worldwide. Over 7,000,000 cases in the US and 205,000 deaths. Pandemic tracker: https://coronavirus.jhu.edu/map.html
• 9 November 2020 – Pfizer – Bio-N-Tech vaccine reported preliminary efficacy of over 90% and buoying humanity (and the markets) into cheers. It requires two sequential injections
• 10 December 2020 – Pfizer/Bio-N-Tech mRNA vaccine approved and deployed initially in Great Britain and
• 15 November 2020 – The US reaches 11 million cases and almost 250,000
• 15 December 2020 – The US reaches 17 million cases and almost 310,000 deaths. Worldwide, over 74 million cases and 1.7 million deaths.
• December 2020 – B.1.1.7 variant emerged in Britain, found to be roughly 50% more infectious. Now detected in more than 70
• Late December 2020 – B.1.351 variant appears in South Africa which decreases the efficacy of AZ vaccine by 20%.
• Late December 2020 – P1 variant detected in Brazil
• 7 Feb 2021 – B.1.1.7 variant is doubling every 10 days in the US
• 11 Feb 2021- Illinois confirms first case of B.1.351
• 15 February 2021 – 28 Million confirmed cases in the US and almost 500,000