Paper and Threads

Now that we are certain that SARS-CoV-2 will be an endemic virus, it is essential that scientists continue to look for medications that might control the infection once symptoms develop.  This week there was an announcement that two "protease inhibitors" that block virus replication in cells are entering Phase 3 trials,   Phase 1 trials assess safety and often test multiple doses.  Phase 2 trials also look for safety and simultaneously look for drug efficacy.  Phase 3 trials are randomized between volunteers receiving the "treatment" and volunteers receiving placebo (RCT).  They are also double blind meaning neither the patient nor the investigators know who is receiving which pills. The trials have just started enrolling subjects.  See Below

Clinical Trials:

Merck is testing the efficacy and safety of the drug Molnupiravir (EIDD-2801) in 1850 non-hospitalized subjects with mild-moderate symptoms, who have test confirmed Covid-19 with at least 1 risk factor for severe disease.  Half of the subjects will receive placebo. Each group will take the medicine every 12 hours for 5 days.

Merck also convened a randomized placebo-controlled trial to test the drug in adults who reside in the same home with an infected Covid-19 patient. The end point will be development of Covid-19 infection in the household contacts within 14 days.

Pfizer is testing their investigational drug Pf-07321332 with Ritonavir (another protease inhibitor) in a randomized placebo controlled double blind trial in 3000 non-hospitalized high risk adult patients with PCR positive Covid-19. Half the volunteers will take placebo.  Subjects will take the pills every 12 hours for 5 days and the efficacy and safety will be assessed.    

Posted by Shirley at 12:02 PM | Permalink | Comments (0)

This is a quote from Dr. Daniel Griffin who says the above on his Podcast every week.  My Grandchildren are going back to school.  Six of them are vaccinated, but two of them are under twelve and will be unvaccinated.  Therefore only classroom mitigation strategies will protect them in school.  There is a mask mandate in NYC schools, but social distancing at 6 feet will be impossible.  And how many schools really have cross ventilation or hepa filters in the classroom?  Most important, how many faculty and staff are vaccinated?  There is a new publication that is worth reading in which an unvaccinated teacher was the source of a delta Covid cluster in Marin County CA.  She only removed her mask to read to the students.  Read below to see the results of very careful studies that were done  

The unvaccinated teacher became symptomatic on May 19th, but thought it was allergies.  She continued to work for 2 days and then had a Covid test on May 21st - which was positive.  On occasion during this time the teacher sometimes read to students without her mask and she was one of 2 teachers in the school who were not vaccinated. There were 12 Covid infections in her students that were confirmed in the class within 5-7 days.  Eight of the 10 students who sat in the first two rows and 4 of 14 students in the last 3 rows developed Covid.  There were also secondary infections of siblings and parents of the original students for a final total of 27 Covid cases. Eighty-one % were symptomatic.  These students all wore masks throughout the day and their desks were 6 feet apart.  Each classroom also had high-efficiency particulate air filters and doors and windows were left open.  Genomic sequencing of 18 of these cases were positive for the delta variant.  Unfortunately the teachers sample could not be retrieved. I hope that school systems will do everything they can to protect the unvaccinated students as schools open all over the country - vaccination mandates and mask mandates as a minimum. 

Posted by Shirley at 6:03 AM | Permalink | Comments (0)

Decisions about a 3rd mRNA vaccine became even more complicated this week.  What is the US trying to achieve with vaccines?  What clinical trial data is available that supports the need of a 3rd dose?  Who should get 3rd doses and when?  What is our obligation to other countries?

1.  Is there enough data to demonstrate that we need it?  Not yet.  The recent information from Israel is not yet published or presented fully.  The breakthrough cases and results from other studies from August will be analyzed for more information with both mRNA vaccines (Israel uses Pfizer).  There are different opinions about the necessity from very good scientists.  And almost always the US "waits for the science" before making a recommendation.

2.  It is estimated that there are a million people who already made a decision and got their 3rd dose, and no data has been collected re: efficacy and safety in a standardized way. 

3.  Pfizer already submitted their proposal to give a third dose.  Today it was reported that Moderna applied to give a 3rd dose, but the amount in the dose is slightly different than their first and second shots.  That may delay their data review and slow their FDA and CDC approval. 

4.  Third doses were approved by both the CDC and FDA for patients with immune deficiency and they are currently being administered. The 3rd dose of the vaccine for the general public needs to be approved by them too.  The FDA VRBPAC meeting is scheduled for September 17th.  The CDC ACIP meeting is not yet on their schedule.  See Below

Other information: 

Israel:  "Israeli officials say their data shows that the potency of Pfizer's vaccine wanes over time against severe disease and hospitalization, but that a third shot bolsters protection significantly.  The FDA wants to see the raw data, to make sure it backs up summaries that the Israeli government has provided."  NYT Sept 3,2021 

Sharing our vaccines with the world:  130 million doses have already been shipped to 90 countries. And 200 million more doses will be shipped before the end of 2021 and another 300 million doses before July 2022.  This is data presented by Dr. Fauci at this week's White House Briefing.  There are also plans for the US to develop and fund more vaccine manufacturing.

Posted by Shirley at 6:06 AM | Permalink | Comments (2)

I spent all of Monday watching the meeting of the CDC Advisory Committee on Immunization and Practices (ACIP).  Most of the day the data submitted for the Pfizer BLA was reviewed very carefully and then the independent experts on the committee voted 14 to 0 and approved the BLA.  From 4-5PM the working group for "3rd shots" discussed a framework for their analysis of and planning for additional doses of the mRNA vaccines and presented recent data from 5 US studies of vaccine efficacy and breakthrough cases.

While there is some waning vaccine efficacy in older people against asymptomatic and mild-moderate Covid infections, vaccine efficacy is still high against severe infections, hospitalizations and deaths.  The working group plans to meet again in mid-September to review new data from the analysis of infections in August when the delta variant took over the other Covid variants in the US.  See Below

Some vaccines require annual "boosters" against mutations (influenza) and other vaccines require a sequence of 3 doses to establish long term immunity  (hepatitis B and human papilloma virus).  Studies performed after a 3rd dose may clarify the best way to establish strong immune responses to SARS-CoV-2.   Immunocompromised patients are currently receiving a 3rd dose, and the next group to be considered may be health care workers, long term care facility patients, and people older than 65.  Both the FDA and CDC will have to carefully consider the data and approve the final plan for more shots.  Stay tuned, and wait for more information in September. 

Posted by Shirley at 4:07 AM | Permalink | Comments (1)