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December 2, 2020

Happy Dance #4 - Moderna Vaccine Data

Monday Moderna released the next batch of data from their phase 3 Vaccine trial that they conducted with the NIH-NIAID.  When they reached a total of 196 Covid-19 cases (out of 30,000 volunteers) the Data Safety and Monitoring Board were allowed to determine how many cases were in the placebo group (185) and how many in the vaccine group (11), a 94% efficacy preventing Covid-19.  When they looked for the first time several weeks ago it was 94.5%.  There were no serious adverse effects- volunteers complained of pain and redness at the injection site, fatigue, muscle and joint aches, and headaches.  There were no serious adverse effects.

Of special note, there were 30 severe cases plus 1 death in the placebo group and none in the vaccine group.  Sometimes vaccinated patients develop worse infections after vaccination, called "vaccine enhancement."  None was seen with this vaccine. The vaccinated group will still be followed for a full 24 months to make sure there are no late side effects. 

The volunteers included 20% Hispanics, 10% blacks, 4% Asians and the efficacy and side effects were the same in all of the subgroups.  There were 33 volunteers over 65 in the Covid-19 group.  

Read Below 


Then Moderna filed an application to the FDA for Emergency Use Authorization.  On Dec 10th the Pfizer application will be reviewed by the VRBPAC, the FDA scientific advisory board.  It is hoped that the FDA VRBPAC will evaluate the Moderna application on Dec. 17th.  As soon as the FDA grants emergency approval, the CDC can approve the distribution of the vaccines.  There may be 40 million doses from both companies for 20 million people (2 doses) by the end of December.  The vaccinated groups of the Phase 3 trials for both vaccines will be completed and published in peer-reviewed medical journals, with much more data.  The FDA will then review the completed trials and make decisions re: Biologic License Applications for final approval. The placebo groups will probably be vaccinated soon, so they can now be protected. 

November 28, 2020

Is Convalescent Plasma of Benefit in Covid-19?

Antibodies from Covid-19 infected patients are of 3 main types: 

1. Convalescent Plasma - donated by a recently recovered patient.

2. Hyperimmune Globulins -the above antibodies that have been partially concentrated and purified.

3.  Monoclonal Antibodies - like the Regeneron Cocktail (2 very specific manufactured antibodies to the spike protein) and the Lilly product which has one specific manufactured antibody.  These were previously discussed here and now both have an Emergency Use Authorization.  Randomized controlled Phase 3 clinical trials are in progress.

The effectiveness of infusing convalescent plasma was never proven because more than 60,000 Covid-19 patients were given without a randomized controlled trial (RCT).  Plasma could be given on a compassionate basis and observational studies are not sufficient to prove benefit.  This week the New England Journal of Medicine published a thorough RCT and proved that convalescent plasma was no better than placebo. 


Results published in New England Journal of Medicine Nov. 24, 2020:  228 patients were randomly assigned to receive convalescent plasma and 105 patients placebo.  The median time from symptoms to enrollment was 8 days, and low oxygen levels were the most frequent reason for the plasma.  Conclusion:  No significant differences were observed in clinical status or overall mortality at 30 days with convalescent plasma. 

For More Information:  The Infectious Disease Society recommends that any patients receiving convalescent plasma should be enrolled in one of the ongoing randomized controlled clinical trials to gather as much data from RCT as possible. 

Published Nov 17, 2020 


November 25, 2020

What You Should Know About Vaccine Distribution

Distribution of the successful vaccines will be a huge challenge.  And the FDA must grant an Emergency Use Authorization (EUA) for each vaccine, when the application is filed by the company, before distribution can begin. The Pfizer application is first reviewed by an independent advisory group, the Vaccine and Related Biologic Products Advisory Committee (VRBPAC) on Dec. 10th.  Members of the committee are drawn from academia, research and clinical practice.  The hearings will be televised on Dec. 10th. 

The VRBPAC can recommend approval of the vaccine, or request more information from the company.  The FDA then makes a final decision, based on the advice from their FDA career scientists and the VRBPAC. 

Once approved, the vaccine distribution plans can begin.  The CDC is in charge of distribution and they have broad recommendations from the National Academies of Sciences, Engineering, and Medicine, who established 4 phases of vaccination beginning with health care workers.  The vaccines will be distributed directly to the states and territories.  The states then need to determine who and how they can immunize the first target group.  State governors have been complaining that they need funds to support the vast organization that will be needed for storage, personnel training, and scheduling the immunizations, and it is not clear that the current gov't is planning to release these additional funds as quickly as necessary.  It is a two dose vaccine and patients will need to be scheduled for the 2nd dose in 3 weeks - which requires careful planning, documentation. and availability of the 2nd dose.  The Pfizer vaccine needs to be maintained at -94 degrees Fahrenheit imposing additional limitations in each state until they each develop their own systems.   Some states are purchasing ultra-cold freezers for large storage and distribution sites, others will rely on dry ice pellets which the vaccine is packed in for shipment from Pfizer.  Read Below




This initial distribution will occur at a time when a new government administration is taking over, including state governors, and there is a surge in cases, and a record number of deaths.  Health care workers are already having difficulty with the increase in hospitalizations.  The US government may be given 20 million doses of the Pfizer vaccine in 2020, for 10 million health care workers (2 doses each) to be divided among the states and territories based on population.  We can only hope this phase of the Pfizer vaccine trial will go smoothly. 

I just scanned an Oct 30th 15 page CDC document of information re: vaccine distribution.  It was a series of answers to questions raised by the state governors and answered by the Dept. of Health and Human Services.  Each state was supposed to develop plans in October.


November 21, 2020

Happy Dance #3

Happy Dance for Pfizer Clinical Trial Results - It was 95% effective!!  There were no serious safety concerns. 

I was awake Wednesday morning when the email from Pfizer arrived in my inbox, just 2 days after Moderna's wonderful preliminary report -  what great news!  The independent Pfizer Data Safety and Monitoring Board (DSMB) broke the blinded study when the number of symptomatic, Covid-19 positive volunteers reached 170 cases.  The number rose quickly from their first look at 94 cases  because of the surge in new cases around the country.  Neither Pfizer, nor the volunteers, knew which group had the positive cases.  The DSMB is a group of scientists and statisticians who are allowed to look at the data at preset intervals.  The results showed that 162 of the infected patients were in the placebo group and 8 were in the vaccinated group, with 9 severe cases in the placebo group and 1 in the vaccinated group (new data since the 1st data review). And 94% of older patients were protected.  Vaccinated patients complained of fatigue and flu-like symptoms, but there were no reported serious adverse effects. 

With these results, Pfizer can now apply for Emergency Use Authorization for the vaccine in order to start vaccinating the placebo group and others.  Health care workers will probably be the 1st group - from the 25  million doses that will come to the US (2 shots per person 21 days apart).   The vaccinated patients will continue to be followed for a full 24 months in order to look for any late adverse effects.  The placebo group will probably be vaccinated as soon as the EUA is received.  Continue reading below.


Pfizer and Moderna vaccines were the first messengerRNA vaccines ever brought to this level, and their effectiveness is very impressive.    This vaccine development platform allowed the mRNA for a portion of the spike protein to be prepared very quickly by Moderna and NIH-National Institute of Allergy and Infections Diseases, with Dr. Tony Fauci as head.  NIH had been studying the coronaviruses for many years, and the spike protein of the virus was known to be the part of the virus which attaches to a receptor on human cells allowing the virus to infect mucosal cells in the nose, trachea and lungs.  

All of the vaccines under development are using techniques to isolate parts of the spike protein and to stimulate the immune system.  There are at least 4 categories of vaccine types, and the mRNA technique is just one of those - the newest.  The messengerRNA (a genetic pattern for a piece of the spike protein)  is prepared and injected into our muscles.  It enters our cells and acts as a template for them to make a small inactive piece of the spike protein.  Our cells then become a factory and as "spike protein" is made, it stimulates an immune response. I find it really fascinating!!

There will be much more information to come from the Pfizer and Moderna studies.  NIH will assess all parts of the immune response in the vaccinated volunteers, which will help scientists to understand the duration of immunity stimulated by the vaccine.  After the FDA receives the EUA application from Pfizer, the scientists appointed to an FDA board will review all of the data and make a decision.  It usually takes weeks for a decision, but the urgency for vaccine approval is such that it may be just a few weeks.  Then distribution can begin.  This will be a topic for another blog post.


November 18, 2020

Happy Dance #2

Happy Dance #2 - Celebrating the preliminary information about the Moderna Vaccine.

I first heard of the National Institutes of Health NIAID/Moderna Vaccine in the Spring, just after the team had created the mRNA.  I was fascinated that a piece of messenger RNA could be made from the Sars-CoV-2 spike protein and injected into animals, and then humans to stimulate our own cells to make the spike protein, which could then turn on our immune response.  The preliminary announcement by Moderna on Monday was very exciting and I'm sure that everyone has heard that the efficacy was 94.5%.   Read Below 


All of the 30,000 volunteers are already enrolled in the clinical trial, and the Data Safety and Monitoring Board (DSMB) was allowed to open the blinded study when a specific number of volunteers had developed symptoms of Covid-19.  They did that last weekend and found that 95 volunteers were Covid-19 positive and 90 of them were in the placebo group.  Additionally 11 cases of severe Covid-19 were in the placebo group and none in the vaccinated group.  The reported adverse symptoms were fever, headache, arm pain, joint and muscle aches - and were transient after the 2 vaccine injections 28 days apart.  Volunteers: 37% of the enrolled group are people of color, 42% are high risk, with comorbidities or are 65+.

The DSMB will next look at the data after a total of approximately 150 cases of Covid-19 occur.  The FDA requires that every vaccine must be >50% effective to apply for FDA approval, and 50% of the volunteers must have been followed for at least 2 months after their second injection. Everyone hopes that it will still remain >90% effective with no cases of severe Covid-19 in the vaccinated group.  If approved, the Phase 3 Clinical Trial can be stopped at that point, although the vaccinated volunteers will be followed for a total of 24 months to make sure it is safe.

All of the data will be reviewed and analyzed, and then an FDA application for an Emergency Use Authorization can be filed.  Once it is approved, the placebo group will be vaccinated and production will be ramped up for distribution.  This mRNA vaccine, unlike the one from Pfizer, requires long term storage at -4 degrees F, but can be kept in a refrigerator for up to one month.