Paper and Threads

It is hard to sort out the various tests available - but they still fall into two categories: molecular tests that amplify and then measure the virus nucleotides, and antigen tests that use a specific antibody to recognize the virus protein in the nasal sample.  Last Saturday the FDA gave Emergency Use Approval (EUA) to a Saliva Molecular Test developed by Yale and used by the NBA.  This would be lots easier, but it probably won't be widely available until they scale up production.

The Point of Care Rapid Tests (POC) are antigen tests, that must be done in Doctors Offices, Clinics, Nursing Homes, etc.  They require machines that have been developed by a company for a specific type of test, and employees must be trained to use the machines.  Antigen tests are not as sensitive as molecular tests.  They are most commonly positive when patients begin shedding virus, and turn negative within 10-14 days.  The molecular tests are positive earlier and remain positive later, even when there is dead virus in the nasopharyngeal swab sample.  Positive antigen tests should be confirmed with a molecular test if there are any questions about the diagnosis. A rapid point of care test can be done immediately, and a molecular test may take more than 4 days to a week to get a result.  The rapid tests mean that infected patients can be quarantined, their contacts traced, and isolated making it easier to control the pandemic.  Continue Reading.

Next post I will describe a rapid at "home test" that is like a pregnancy test.  But this test needs a special FDA approval and the FDA will have to give emergency use approval as a public health tool instead of a highly sensitive and reproduceable molecular diagnostic test. 

Posted by Shirley at 7:29 AM | Permalink | Comments (0)

Coronavirus testing can be done by PCR, a method to detect the genetic material of the virus, or by detecting the antigen of the virus.  The tests have different sensitivities, PCR can detect the virus when the viral load is too low to be easily passed on - or when it is detected at the end of the infection when only remnants of the virus are present.  The antigen tests are less sensitive and at the onset of the infection may be falsely negative.  But these tests can be done quickly, and in Nursing Homes, Medical Offices, and other places that have the machines and some training.

It is taking many days to get the results of the PCR test results almost everywhere, and this is unacceptable. if the tests are being done to quarantine infected people to prevent further spread, it is too late to have an impact on the infection rate.  The antigen tests are more rapid, but may need to be repeated and confirmed with a PCR test - depending on the circumstances.  Read more below.

In order to get PCR tests back faster it is possible to pool samples from different people if the virus levels in the community are low.  NYC is testing 1000s of people every day and only 1% of the tests are positive.  If samples were pooled, here from 5 people for example, and the pooled sample tested negative, time and supplies could be saved.  If the pooled sample is positive, each sample would need to be tested.  But if the pool were larger and negative, even more time and supplies would be saved. Right now in states with a high percentage of positive tests, pooling wouldn't be feasible.  But if infected patients could be identified, isolated, and their contacts tested faster, we might be able to control the pandemic better. Is there a will to do this in our country?

Could we ever have at home tests, like a pregnancy test, that cost only $1-2, and could be done each day?  They were developed, tested, and can identify patients at the time they are infective.  But it is unclear where the funding would come from to scale up these tests. We can't even get our country to wear masks to decrease the number of infections.

Next time Point of Care Antigen Tests and Rapid At Home Tests. 

Posted by Shirley at 8:34 AM | Permalink | Comments (1)

How many New York City Schools Will Reopen? 

New York City has < 1% positive Covid-19 tests each day, so the virus is being controlled.  And yet we worry about our students returning to school and getting infected.  There is not enough space for social distancing, and in older schools the ventilation may not be adequate. I volunteer in a school in the Bronx that was built in the late 1800s. 

Will there be an adequate number of teachers who are willing to return to the classroom, especially if they have underlying health risks or are in the vulnerable age groups?  This morning on NPR teachers were saying they really want to be with their students, but they have to feel safe.  Students and teachers will be required to wear masks all day, to remain socially distanced, and wash their hands frequently. 

Because of the lack of space, students will attend schools in smaller groups, perhaps 3 days one week, and 2 the next - and the other days will be virtual learning.  Earlier this summer 70% of schools did not have a full time nurse.  Many children in the public schools receive breakfast and lunch while at school.  They will eat their meals in their classrooms so students will not be in large groups in the cafeteria.  On the days when they are not in school, many students will need city-sponsored child care because they have  parents who are essential workers.  None of the plans are confirmed, and my grandchildren may not hear about the final plans until several days before school opens.  Read More Below.

It would be wonderful if there were very cheap "at home" Covid-19 virus tests that could easily be done in the morning before students and teachers leave for school.  If positive, they would stay home.  There is good scientific data on these tests, and there is now a ground swell to get the FDA to give Emergency Use Approval (EUA) to them.  If approved, manufacturers can quickly make them available.   I hope to gather more information on these tests, which are similar to home pregnancy tests, later in this week.  Current tests that take many days to get results can't help us control the epidemic.

Posted by Shirley at 8:36 AM | Permalink | Comments (0)

Yesterday Richard Engel NBC National News, announced that scientists at Oxford's Jenner Institute in the UK are currently discussing a Challenge Trial of their Oxford AstraZeneca vaccine.  The vaccine is now in Phase 3 Clinical Trials in multiple countries.  There are many ethical arguments against a Challenge Trial in which all volunteers are vaccinated, and then several months later are given a measured, calculated dose of SARS-CoV-2 virus.  Oxford could enroll 40-60 volunteers and determine vaccine effectiveness in much less time. They say the Challenge Trial, which would be done in healthy 20 year olds, will have "minimal risks."  Vaccine Challenge Trials raise ethical questions, but were done previously for other pathogens. The problem in this instance, is the lack of effective treatment for those volunteers who do develop Covid-19?

Continue Reading Below: 

Oxford AstraZeneca's standard Phase 3 randomized control trial is enrolling 30,000 volunteers - half will receive the vaccine and half will receive placebo.  No one including the patient will know what each volunteer receives until the end of the trial.  But if the volunteers aren't regularly exposed to the virus, it will take months to figure out the effectiveness of the vaccine.  Trial participants are told to lead their normal lives, but the trial will depend on them being exposed where virus infections are high.  The success of the vaccine is based on the number of cases of Covid-19 in the vaccinated group vs the placebo group.  In the US Moderna and Pfizer are also in Phase 3 testing with 30,000 volunteers.

Posted by Shirley at 6:37 AM | Permalink | Comments (0)

New York Times Aug 2:  "Scientists Worry About Political Influence Over Coronavirus Vaccine Project"  A horrifying article!  "Emergency Use Authorization" to make vaccine available in October, before the Phase 3 vaccine trial is complete, and that is required for FDA approval.  Continue reading....

This is long, but really important.  I am writing as a retired MD, who has experience with Clinical Trials for cancer treatment.  It is dangerous to make assumptions on Trial conclusions from incomplete data. 

There is great fear that there will be political pressure to release the front runner vaccines in October with an emergency use authorization (EUA).  I watched 6 hours of hearings by the House Energy and Commerce Subcommittee several weeks ago, and the 5 Vaccine Company representatives were asked over and over how they were going to insure the vaccines will be safe.  I watched an hour long interview of Dr. Stephen Hahn, by Dr. Howard Bauchner, last week.  Hahn is the FDA Commissioner and Bauchner is the editor of JAMA.  The Vaccine companies said that the Phase 3 Trials would not be rushed and safety compromised.  Dr.Hahn said that panels of vaccine scientists just worked on a set of standards that must be met in order to approve a vaccine - and this was done so any decision will be made based "only on the scientific data."

There was a very long article in the New York Times Aug 2nd, that was picked up by other news sites. They say there is a lot of political pressure to get a vaccine approved in October.  It says that if the FDA won't give "Emergency Use Authorization," the secretary of HHS in the White House can overrule his decision.  I recommend caution for the following reasons- and I usually take vaccines without worry.

1.  The two major US vaccines, Moderna-NIAID and Pfizer BioNtech, each began their phase 3 trials the last week in July. Moderna just published results of their Phase 1 Trial in NEJM (peer reviewed).  There were only 45 subjects vaccinated, evaluated, and reported.  They have not yet released their Phase 2 data.  I can't find any data from Pfizer as of today.  I assume they have completed Phase 1 and Phase 2 trials, although volunteers are usually followed for 1-2 years for late side effects.

2.  Moderna and Pfizer are part of Operation Warp Speed, and committed to test 30,000 volunteers in a Phase 3 trial.  Half of the volunteers will be vaccinated and half will get a placebo injection.  But no one will know who received which injection.  Volunteer enrollment just began( July 23 and 27).

3.  Each volunteer will get two doses, days 1 and 29 (Moderna) and days 1 and 21 Pfizer, so if they are enrolling volunteers beginning in August, the last volunteers enrolled will be getting their vaccinations in late August, September or even later.  By October those patients may not be followed long enough to adequately assess safety and efficacy! 

4.  The FDA will require that each vaccine will have a minimum of 50% efficacy (preferably >70%) in preventing Covid-19in the vaccinated group and acceptable adverse effects. Many tests to rate the immune response need to be done in specialized research labs and will take time.  These are blinded studies, and there are oversight committees set up who could stop the study if adverse effects are serious.

5.  If an EUA were granted due to political pressure, I wouldn't get that vaccine until the patients were all enrolled, followed for awhile, and preliminary results analyzed.  I want the vaccinated subjects to have at least 50% protection from Covid-19  when compared to the placebo group - AND side effects to be limited to injection site pain and flu-like symptoms. 

I'd also want to see careful review by other scientists.  The mumps vaccine set the speed record for vaccine development - 4 years. New technology made rapid vaccine development possible - both of these vaccines are made from the coronavirus spike protein genetic sequence and our cells make a spike protein which stimulates our immune system.  Older vaccines were made with inactive viruses or proteins of the virus.

Posted by Shirley at 7:40 AM | Permalink | Comments (1)