Medical Bits – Vol. 3.3: Your Health and Medical News
We have reviewed the origins of the novel coronavirus responsible for the pandemic on prior “Bits”. The initial reports of a zoonotic disease affecting bats and probably pangolins as an intermediate host and spreading from “wet-markets” in the Hubei province of China and probably centered in Wuhan have now been further corroborated (although not all mysteries have been solved).
More than 3 million humans (likely at least double) have died as a result of the SARS-CoV2 Pandemic as of April 2021. Sadly, many other public health priorities have been neglected as a result of the pandemic, resulting in additional suffering, diseases and deaths. According to the World Health Organization, an additional 500,000 people may have died from Tuberculosis alone in 2020; Measles cases approached a million, leading to an estimated 210,000 deaths (mostly in infants). Cases of Poliomyelitis doubled and HIV in Sub-Saharan Africa multiplied, as reported in Nature this past week. Immunization and public health campaigns for other ailments worldwide have been upended and Health budgets decimated. And many people in this country have ignored their own problems and healthy routines (gaining on average 12-15 lbs.), skipping check-ups and preventive care! Yet, we should all be smiling and content that the worse in our part of the world, is likely behind.
At this time, there are ten vaccines against COVID-19 approved in different nations and 26 different vaccines making progress at the final Phase III clinical trials. In the US, three vaccines have received Emergency Use Authorization (EUA). Two mRNA vaccines were deployed in December 2020. The Pfizer – BioNTech and the Moderna – NIH-NIAID and received preliminary approval and EUA. 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. By the end of May 2021, the Novavax vaccine is anticipated to be approved, as the pivotal trials being completed in the US, Mexico and the UK are concluded. 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.
You have all read about the few complications induced by the adenovirus vector-based DNA vaccines (Ad26.COV2.S – J&J approved in the US and ChAdOx1nCov-19 – Oxford-AZ approved in the EU) leading to a pause in administration. The mechanism driving these rare complications have now been elucidated. These vector-based vaccines appear to trigger IgG antibodies that recognize a receptor (Platelet Factor 4-PF4) in the surface of platelets (cells that aggregate to form clots and stop bleeding). The activation of platelets leads to the formation of innumerable clots within the circulation in unusual places.
Additional cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) have now been reported to both, European and US agencies, with 230 cases among 34 million recipients of the Oxford-AZ vaccine; 35 cases in 54 million recipients of Pfizer-BioNTech mRNA vaccine; 5 cases among 4 million vaccinated with the Moderna mRNA vaccine and 6 cases were described among over 7 million who received the J&J vaccine. It appears to be a wider phenomenon and not just related to the vector-based vaccines and as we scrutinize those immunized, the recognition of these phenomena is likely to rise.
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!
Thus, on April 23, 2021, the FDA authorized the resumption of vaccination with the single-shot Johnson & Johnson vaccine and we anticipate further progress in the all-important Pandemic Vaccination campaign.
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.
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 1.2 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 consortiums 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 are all EXTREMELY EFFECTIVE and all appear to make serious disease very rare!
Out of more than 75 million fully vaccinated Americans, “breakthrough” infections occurred in less than 0.008%, hospitalizations in 0.0005% and deaths in 0.0001%! And even in Nursing Homes a recent report from the CDC indicates very low risk of disease after vaccination.
An article published this past week, reports that in a cohort of 417 fully vaccinated individuals with the mRNA vaccines only 2 people developed disease with variants (E484K and B1.526 mutants). The study also confirmed that adequate titers of neutralizing antibodies persist for more than 6 months after immunization and likely much longer.
Also, data from the clinical trials indicates that infectivity in those vaccinated is decreased by at least 70%. Information from Israel suggests that in the few individuals that develop infection after vaccination, the viral load is much lower, making them less infectious.
Additional data now published demonstrates that the mRNA vaccines appear to be protective earlier than initially reported and achieve over 92% protection within 2 weeks of the 1st dose.
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).
A new variant, B.1.617 initially detected in India in late 2020 that has new “dual” mutations –E484Q and L452R – is likely fueling their explosive epidemic, as they appear to increase transmission and possibly reduce the neutralization power achieved with vaccinations. Active surveillance (and your vigilance) continue.
We should emphasize that the immunogenic response and titers of antibodies induced by vaccination are effective. And the good news is that science is keeping up with these mutants. If these “bad guys” are able to cause breakthrough infections in vaccinated individuals, we may need a vaccine “update” or booster within a few months. For an excellent review of New Variants and Mutations.
And a summary from the NEJM follows in this table.
Inoculations are proceeding well and ahead of anticipated goals.
For specific immunization plans review your state:
Maryland – for vaccine registration.
District of Columbia – for vaccine registration or call 855-363-0333.
Virginia – new comprehensive website.
Select CVS Pharmacies (according to local vaccination guidelines).
Select Walgreens Pharmacies (according to local vaccination guidelines).
This NYT link has National and International Vaccine Rollout information.
DEBUNKING MYTHS: Q & A
1. What do you think about a Vaccine Passport?
I fully support the idea. It has to be properly implemented with an accurate database. If some people do not want to be vaccinated, we respect them. But certain public venues, use of public transportation or attending schools/colleges should be off limits to them. The same rule should apply to other potentially deadly infectious diseases. But civil liberties and counter-arguments will likely arise.
2. Pregnancy is 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 my recommendation is to inoculate in the second trimester, to ascertain protection to the mother in the third trimester (when infectious complications may happen as immunity against some viral illnesses decreases by pregnancy) and to facilitate the transfer of antibodies to the baby through the placenta and achieve at least partial protection to the newborn.
3. Do I need to use a mask while exercising outdoors?
No. This is a respiratory virus and the likelihood of contracting disease outdoors while exercising and in movement is remote or non-existent. If surrounded by crowds without distancing, best to don your mask.
4. Do I need to continue to decontaminate surfaces?
No. As we learn more about transmission, we know that this is an airborne disease, with the virus aerosolized by sick individuals into the surrounding air and transmissible mostly indoors or among crowds outdoors. It is highly unlikely that we can pick up an “infectious dose” on our fingertips.
5. How long hospitalized 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 longer in immunocompromised patients.
6. 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 a few weeks later. If you are “hoarding” an oxygen concentrator, have your physician return it and use those precious healthcare funds for other beneficial treatments.
7. 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. It is very difficult to compare clinical trials, as all have different parameters, antigen dosing, interval between injections and population studied. We should be ready to accept any vaccine that comes our way!
8. 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 the Vaccine-associated clotting (VITT) complications reported above occur to about 1:200,000 people and we now know how to recognize them and treat effectively.
9. What is the duration of the protection elicited by vaccines?
The protection is anticipated to last at least 6-12 months and possibly a lot longer as the cellular immunity is stimulated as well and it is a long-lasting defense.
10. 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 thousands of folds.
11. 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.
12. 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 economical and faster.
13. 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.
14. 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.
15. Do antibodies last and could I get re-infected with COVID-19?
The fact that after millions of cases worldwide only a few cases of re-infection have been reported is good news. Antibodies last several months and our cellular immunity takes over after antibody titers wane. 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
16. 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, may go on to develop small clots and disseminated intravascular coagulation. For those patients, anticoagulation treatment may be warranted and decided by the ICU team at the time of care. Use of preventive blood thinners is unfounded!
17. Is the virus mutating to be able to be infectious through the skin?
No! There is no evidence that this is possible. 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.
18. 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 possibly severity of illness in few cases. 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 are now at work such as B.1.1.7 which are displacing other less “efficient” strains. But vaccines are effective and if booster doses “updates” are necessary, you will be ready to get another JAB!
19. 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
20. 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 illness. 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).
21. 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 (mine: do it earlier!)
22. 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.
23. When will vaccines become available for Children?
The clinical trials that lead to the approval of the mRNA vaccines included adolescents ages 12-17. As of now, everyone older than 16 can be vaccinated. Those 12-15 will likely be approved for vaccination within the next month, as the data regarding safety and efficacy is robust. Children ages 6 months to11 years may have to wait till the early fall as the results of the trials initiated in early March 2021 become available.
WHAT CAN YOU DO TO LIMIT THE SPREAD OF DISEASE AND HELP CURB THE PANDEMIC?
1. Get vaccinated as soon as possible!!!
2. Help educate your family members, friends, neighbors and anyone out there who has any remaining doubts about the importance of vaccination!!!
3. As Mahatma Gandhi said: “You must be the change you want to see in the World” and “Happiness, is when what you think, what you say and what you do are in Harmony”.
We, The People, have a social responsibility to educate, help each other and promote best practices.
Allow me to repeat:
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!
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 and it is passing! The worse is behind! 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 your taxes coming due May 17th)
The only fountain of youth proven by science and experience are exercise, laughter, humor and a good positive attitude!
Let’s try and 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